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Shen L, Chen M, Su Y, Bi Y, Shu G, Chen W, Lu C, Zhao Z, Lv L, Zou J, Chen X, Ji J. NIR-II Imaging for Tracking the Spatiotemporal Immune Microenvironment in Atherosclerotic Plaques. ACS NANO 2024; 18:34171-34185. [PMID: 39630481 DOI: 10.1021/acsnano.4c10739] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/18/2024]
Abstract
The inflammatory immune microenvironment is responsible for atherosclerotic plaque erosion and rupture. Near-infrared-II (NIR-II) fluorescence imaging has the potential to continuously monitor the spatiotemporal changes in the plaque immune microenvironment. Herein, we constructed three different NIR-II probes based on benzo[1,2-c;4,5-c']bis[1,2,5]thiadiazole-4,7-bis(9,9-dioctyl-9H-fluoren-2-yl)thiophene (denoted as BBT-2FT): VHPK/BBT-2FT NPs, where VHPK is a specific peptide targeting vascular cell adhesion molecule-1; iNOS/BBT-2FT NPs for modulating the polarization of M1 macrophages by inducible NO synthase (iNOS) antibodies; and Arg-1/BBT-2FT for counterbalancing the inflammatory responses of M1 macrophages. These tracers enable precise tracking of atherosclerotic plaques and M1 and M2 macrophages through NIR-II imaging. VHPK/BBT-2FT NPs can accurately trace atherosclerotic plaques at various stages. Arg-1/BBT-2FT NPs precisely located M2 macrophages in the early plaque microenvironment with upregulation of peroxisome proliferator-activated receptor γ (PPAR-γ), signal transducer and activator of transcription (STAT) 6, and ATP-binding cassette transporter A1 (ABCA1), indicating that M2 macrophage polarization is crucial for early plaque lipid clearance. Meanwhile, iNOS/BBT-2FT NPs accurately tracked M1 macrophages in the advanced plaque microenvironment. The results showed that M1 macrophage polarization induces the formation of an inflammatory microenvironment through anaerobic glycolytic metabolism and pyroptosis in the advanced hypoxic plaque microenvironment, as indicated by the upregulation of hypoxia-inducible factor 1 alpha (HIF-1α), STAT1, NOD-, LRR-, and pyrin domain-containing protein 3 (NLRP3), pyruvate dehydrogenase kinase 1 (PDK1), and glucose transporter 1 (GLUT-1). Combining immunological approaches with NIR-II imaging has revealed that hypoxia-induced metabolic reprogramming of macrophages is a key factor in dynamic changes in the immune microenvironment of atherosclerotic plaques. Furthermore, our strategy shows the potential for real-time diagnosis and clinical prevention of unstable plaque rupture in atherosclerosis.
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Affiliation(s)
- Lin Shen
- Key Laboratory of Imaging Diagnosis and Minimally Invasive Intervention Research, Imaging Diagnostic and Interventional Minimally Invasive Institute, The Fifth Affiliated Hospital of Wenzhou Medical University, No 289, Kuocang Road, Lishui 323000, China
| | - Minjiang Chen
- Key Laboratory of Imaging Diagnosis and Minimally Invasive Intervention Research, Imaging Diagnostic and Interventional Minimally Invasive Institute, The Fifth Affiliated Hospital of Wenzhou Medical University, No 289, Kuocang Road, Lishui 323000, China
| | - Yanping Su
- Key Laboratory of Imaging Diagnosis and Minimally Invasive Intervention Research, Imaging Diagnostic and Interventional Minimally Invasive Institute, The Fifth Affiliated Hospital of Wenzhou Medical University, No 289, Kuocang Road, Lishui 323000, China
| | - Yanran Bi
- Key Laboratory of Imaging Diagnosis and Minimally Invasive Intervention Research, Imaging Diagnostic and Interventional Minimally Invasive Institute, The Fifth Affiliated Hospital of Wenzhou Medical University, No 289, Kuocang Road, Lishui 323000, China
| | - Gaofeng Shu
- Key Laboratory of Imaging Diagnosis and Minimally Invasive Intervention Research, Imaging Diagnostic and Interventional Minimally Invasive Institute, The Fifth Affiliated Hospital of Wenzhou Medical University, No 289, Kuocang Road, Lishui 323000, China
| | - Weiqian Chen
- Key Laboratory of Imaging Diagnosis and Minimally Invasive Intervention Research, Imaging Diagnostic and Interventional Minimally Invasive Institute, The Fifth Affiliated Hospital of Wenzhou Medical University, No 289, Kuocang Road, Lishui 323000, China
| | - Chenying Lu
- Key Laboratory of Imaging Diagnosis and Minimally Invasive Intervention Research, Imaging Diagnostic and Interventional Minimally Invasive Institute, The Fifth Affiliated Hospital of Wenzhou Medical University, No 289, Kuocang Road, Lishui 323000, China
| | - Zhongwei Zhao
- Key Laboratory of Imaging Diagnosis and Minimally Invasive Intervention Research, Imaging Diagnostic and Interventional Minimally Invasive Institute, The Fifth Affiliated Hospital of Wenzhou Medical University, No 289, Kuocang Road, Lishui 323000, China
| | - Lingchun Lv
- Department of Cardiovascular Medicine, The Fifth Affiliated Hospital of Wenzhou Medical University, Lishui 323000, China
| | - Jianhua Zou
- Departments of Diagnostic Radiology Surgery, Chemical and Biomolecular Engineering, and Biomedical Engineering, Yong Loo Lin School of Medicine and College of Design and Engineering, National University of Singapore, Singapore 119074, Singapore
- Nanomedicine Translational Research Program, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117597, Singapore
- Theranostics Center of Excellence (TCE), Yong Loo Lin School of Medicine, National University of Singapore, 11 Biopolis Way, Helios 138667, Singapore
| | - Xiaoyuan Chen
- Departments of Diagnostic Radiology Surgery, Chemical and Biomolecular Engineering, and Biomedical Engineering, Yong Loo Lin School of Medicine and College of Design and Engineering, National University of Singapore, Singapore 119074, Singapore
- Clinical Imaging Research Centre, Centre for Translational Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117599, Singapore
- Nanomedicine Translational Research Program, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117597, Singapore
- Theranostics Center of Excellence (TCE), Yong Loo Lin School of Medicine, National University of Singapore, 11 Biopolis Way, Helios 138667, Singapore
- Institute of Molecular and Cell Biology, Agency for Science, Technology, and Research (A*STAR), 61 Biopolis Drive, Proteos, Singapore 138673, Singapore
- Department of Pharmacy and Pharmaceutical Sciences, National University of Singapore, Lower Kent Ridge Road, 4 Science Drive 2, Singapore 117544, Singapore
| | - Jiansong Ji
- Key Laboratory of Imaging Diagnosis and Minimally Invasive Intervention Research, Imaging Diagnostic and Interventional Minimally Invasive Institute, The Fifth Affiliated Hospital of Wenzhou Medical University, No 289, Kuocang Road, Lishui 323000, China
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Li Y, Feng Q, Wang L, Gao X, Xi Y, Ye L, Ji J, Yang X, Zhai G. Current targeting strategies and advanced nanoplatforms for atherosclerosis therapy. J Drug Target 2024; 32:128-147. [PMID: 38217526 DOI: 10.1080/1061186x.2023.2300694] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/16/2023] [Accepted: 12/24/2023] [Indexed: 01/15/2024]
Abstract
Atherosclerosis is one of the major causes of death worldwide, and it is closely related to many cardiovascular diseases, such as stroke, myocardial infraction and angina. Although traditional surgical and pharmacological interventions can effectively retard or slow down the progression of atherosclerosis, it is very difficult to prevent or even reverse this disease. In recent years, with the rapid development of nanotechnology, various nanoagents have been designed and applied to different diseases including atherosclerosis. The unique atherosclerotic microenvironment with signature biological components allows nanoplatforms to distinguish atherosclerotic lesions from normal tissue and to approach plaques specifically. Based on the process of atherosclerotic plaque formation, this review summarises the nanodrug delivery strategies for atherosclerotic therapy, trying to provide help for researchers to understand the existing atherosclerosis management approaches as well as challenges and to reasonably design anti-atherosclerotic nanoplatforms.
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Affiliation(s)
- Yingchao Li
- Department of Pharmaceutics, Shandong University, Jinan, Shandong, P.R. China
| | - Qixiang Feng
- Department of Pharmaceutics, Shandong University, Jinan, Shandong, P.R. China
| | - Luyue Wang
- Department of Pharmaceutics, Shandong University, Jinan, Shandong, P.R. China
| | - Xi Gao
- Department of Pharmaceutics, Shandong University, Jinan, Shandong, P.R. China
| | - Yanwei Xi
- Department of Pharmaceutics, Shandong University, Jinan, Shandong, P.R. China
| | - Lei Ye
- Department of Pharmaceutics, Shandong University, Jinan, Shandong, P.R. China
| | - Jianbo Ji
- Department of Pharmaceutics, Shandong University, Jinan, Shandong, P.R. China
| | - Xiaoye Yang
- Department of Pharmaceutics, Shandong University, Jinan, Shandong, P.R. China
| | - Guangxi Zhai
- Department of Pharmaceutics, Shandong University, Jinan, Shandong, P.R. China
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Voicu G, Mocanu CA, Safciuc F, Rebleanu D, Anghelache M, Cecoltan S, Droc I, Simionescu M, Manduteanu I, Calin M. VCAM-1 targeted nanocarriers of shRNA-Smad3 mitigate endothelial-to-mesenchymal transition triggered by high glucose concentrations and osteogenic factors in valvular endothelial cells. Int J Biol Macromol 2024; 281:136355. [PMID: 39374726 DOI: 10.1016/j.ijbiomac.2024.136355] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/17/2024] [Revised: 10/02/2024] [Accepted: 10/04/2024] [Indexed: 10/09/2024]
Abstract
Endothelial to mesenchymal transition (EndMT) of valvular endothelial cells (VEC) is a key process in the development and progression of calcific aortic valve disease (CAVD). High expression of the Smad3 transcription factor is crucial in the transition process. We hypothesize that silencing Smad3 could hinder EndMT and provide a novel treatment for CAVD. We aimed at developing nanoparticles encapsulating short-hairpin (sh)RNA sequences specific for Smad3 targeted to the aortic valve. We synthesized VCAM-1-targeted lipopolyplexes encapsulating shRNA-Smad3 plasmid (V-LPP/shSmad3) and investigated their potential to reduce the EndMT of human VEC. VEC incubation in a medium containing high glucose concentrations and osteogenic factors (HGOM) triggers EndMT and increased expression of Smad3. Exposed to lipopolyplexes, VEC took up efficiently the V-LPP/shSmad3. The latter reduced the EndMT process in VEC exposed to HGOM by downregulating the expression of αSMA and S100A4 mesenchymal markers and increasing the expression of the CD31 endothelial marker. In vivo, V-LPP/shSmad3 accumulated in the aortic root and aorta of a murine model of atherosclerosis complicated with diabetes, without affecting the liver and kidney function. The results suggest that targeting activated VEC with lipopolyplexes to silence Smad3 could be an effective, novel treatment for CAVD mediated by the EndMT process.
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Affiliation(s)
- Geanina Voicu
- "Medical and Pharmaceutical Bionanotechnologies" Department, Institute of Cellular Biology and Pathology "Nicolae Simionescu" of the Romanian Academy, 050568 Bucharest, Romania
| | - Cristina Ana Mocanu
- "Medical and Pharmaceutical Bionanotechnologies" Department, Institute of Cellular Biology and Pathology "Nicolae Simionescu" of the Romanian Academy, 050568 Bucharest, Romania
| | - Florentina Safciuc
- "Medical and Pharmaceutical Bionanotechnologies" Department, Institute of Cellular Biology and Pathology "Nicolae Simionescu" of the Romanian Academy, 050568 Bucharest, Romania
| | - Daniela Rebleanu
- "Medical and Pharmaceutical Bionanotechnologies" Department, Institute of Cellular Biology and Pathology "Nicolae Simionescu" of the Romanian Academy, 050568 Bucharest, Romania
| | - Maria Anghelache
- "Medical and Pharmaceutical Bionanotechnologies" Department, Institute of Cellular Biology and Pathology "Nicolae Simionescu" of the Romanian Academy, 050568 Bucharest, Romania
| | - Sergiu Cecoltan
- "Medical and Pharmaceutical Bionanotechnologies" Department, Institute of Cellular Biology and Pathology "Nicolae Simionescu" of the Romanian Academy, 050568 Bucharest, Romania
| | - Ionel Droc
- Central Military Hospital "Dr. Carol Davila", Cardiovascular Surgery Clinic, Bucharest, Romania
| | - Maya Simionescu
- "Medical and Pharmaceutical Bionanotechnologies" Department, Institute of Cellular Biology and Pathology "Nicolae Simionescu" of the Romanian Academy, 050568 Bucharest, Romania
| | - Ileana Manduteanu
- "Medical and Pharmaceutical Bionanotechnologies" Department, Institute of Cellular Biology and Pathology "Nicolae Simionescu" of the Romanian Academy, 050568 Bucharest, Romania
| | - Manuela Calin
- "Medical and Pharmaceutical Bionanotechnologies" Department, Institute of Cellular Biology and Pathology "Nicolae Simionescu" of the Romanian Academy, 050568 Bucharest, Romania.
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Tong J, Wang Z, Zhang J, Gao R, Liu X, Liao Y, Guo X, Wei Y. Advanced Applications of Nanomaterials in Atherosclerosis Diagnosis and Treatment: Challenges and Future Prospects. ACS APPLIED MATERIALS & INTERFACES 2024; 16:58072-58099. [PMID: 39432384 DOI: 10.1021/acsami.4c13607] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 10/23/2024]
Abstract
Atherosclerosis-induced coronary artery disease is a major cause of cardiovascular mortality. Clinically, conservative treatment strategies for atherosclerosis still focus on lifestyle interventions and the use of lipid-lowering and anticoagulant medications. Despite achieving some therapeutic effects, these approaches are limited by low bioavailability, long intervention periods, and significant side effects. With the advancement of nanotechnology, nanomaterials have demonstrated extraordinary potential in the biomedical field. Their excellent biocompatibility, surface modifiability, and high targeting capability not only enable efficient diagnosis of plaque progression but also allow precise drug delivery within atherosclerotic plaques, significantly enhancing drug bioavailability and reducing systemic side effects. Here, we systematically review the current research progress of nanomaterials in the field of atherosclerosis to summarize not only the types of nanomaterials but also their applications in both the diagnosis and treatment of atherosclerosis. Notably, in the context of plaque therapy, we provide a comprehensive overview of current nanomaterial applications based on their targeted therapeutic systems for different cell types within plaques. Additionally, we address the persistent challenge of clinical translation of nanomaterials by summarizing current issues and providing directions for innovation and improvement in nanomaterial design. Overall, we believe that this review systematically summarizes the applications and challenges of biomedical nanomaterials in atherosclerosis diagnosis and therapy, thereby offering insights and references for the development of therapeutic materials for atherosclerosis.
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Affiliation(s)
- Junran Tong
- Department of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
- Hubei Key Laboratory of Biological Targeted Therapy, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
- Hubei Engineering Research Center for Immunological Diagnosis and Therapy of Cardiovascular Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
| | - Zhiwen Wang
- Department of Nephrology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
| | - Jiahui Zhang
- Department of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
- Hubei Key Laboratory of Biological Targeted Therapy, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
- Hubei Engineering Research Center for Immunological Diagnosis and Therapy of Cardiovascular Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
| | - Ran Gao
- Department of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
- Hubei Key Laboratory of Biological Targeted Therapy, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
- Hubei Engineering Research Center for Immunological Diagnosis and Therapy of Cardiovascular Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
| | - Xiangfei Liu
- Department of Cardiology, Beijing Hospital, National Center of Gerontology, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing, 100005, China
| | - Yuhan Liao
- Department of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
- Hubei Key Laboratory of Biological Targeted Therapy, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
- Hubei Engineering Research Center for Immunological Diagnosis and Therapy of Cardiovascular Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
| | - Xiaopeng Guo
- Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
| | - Yumiao Wei
- Department of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
- Hubei Key Laboratory of Biological Targeted Therapy, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
- Hubei Engineering Research Center for Immunological Diagnosis and Therapy of Cardiovascular Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
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Fournier AP, Morvan MI, Martinez de Lizarrondo S, Gauberti M. Immuno-MRI for Stroke Diagnosis and Prognosis. Neuroscience 2024; 550:53-61. [PMID: 38141809 DOI: 10.1016/j.neuroscience.2023.12.007] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/09/2023] [Revised: 12/12/2023] [Accepted: 12/18/2023] [Indexed: 12/25/2023]
Abstract
Following a stroke, an inflammatory response occurs, characterized by an increased blood-brain barrier permeability, expression of endothelial trafficking molecules, and infiltration of immune cells. Adhesion molecules expressed on activated brain endothelial cells are potential biomarkers of intraparenchymal inflammation. However, in current clinical practice, it is not possible to measure endothelial activation using clinically available imaging. Using targeted micro-sized particles of iron oxide (MPIO), immuno-MRI enables the detection of endothelial adhesion molecules at high resolution and, consequently, facilitates the detection of stroke-induced brain inflammation. In this review, we highlight the most recent studies that used immuno-MRI in models of neurovascular disorders, including transient ischemic attack, ischemic stroke, intracranial hemorrhage, and subarachnoid hemorrhage. We also discuss the potential of immuno-MRI in clinical practice and the necessary next steps for its implementation in patients.
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Affiliation(s)
- Antoine Philippe Fournier
- Normandie Université, UNICAEN, INSERM, PhIND (Physiopathology and Imaging of Neurological Disorders), Institut Blood and Brain @ Caen-Normandie, Cyceron, 14000 Caen, France.
| | - Marion Isabelle Morvan
- Normandie Université, UNICAEN, INSERM, PhIND (Physiopathology and Imaging of Neurological Disorders), Institut Blood and Brain @ Caen-Normandie, Cyceron, 14000 Caen, France
| | - Sara Martinez de Lizarrondo
- Normandie Université, UNICAEN, INSERM, PhIND (Physiopathology and Imaging of Neurological Disorders), Institut Blood and Brain @ Caen-Normandie, Cyceron, 14000 Caen, France
| | - Maxime Gauberti
- Normandie Université, UNICAEN, INSERM, PhIND (Physiopathology and Imaging of Neurological Disorders), Institut Blood and Brain @ Caen-Normandie, Cyceron, 14000 Caen, France; CHU Caen, Department of Diagnostic Imaging and Interventional Radiology, CHU de Caen Côte de Nacre, Caen, France
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Wang J, Zhang H, Wan W, Yang H, Zhao J. Advances in nanotechnological approaches for the detection of early markers associated with severe cardiac ailments. Nanomedicine (Lond) 2024; 19:1487-1506. [PMID: 39121377 PMCID: PMC11318751 DOI: 10.1080/17435889.2024.2364581] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/01/2024] [Accepted: 05/31/2024] [Indexed: 08/11/2024] Open
Abstract
Mortality from cardiovascular disease (CVD) accounts for over 30% of all deaths globally, necessitating reliable diagnostic tools. Prompt identification and precise diagnosis are critical for effective personalized treatment. Nanotechnology offers promising applications in diagnostics, biosensing and drug delivery for prevalent cardiovascular diseases. Its integration into cardiovascular care enhances diagnostic accuracy, enabling early intervention and tailored treatment plans. By leveraging nanoscale innovations, healthcare professionals can address the complexities of CVD progression and customize interventions based on individual patient needs. Ongoing advancements in nanotechnology continue to shape the landscape of cardiovascular medicine, offering potential for improved patient outcomes and reduced mortality rates from these pervasive diseases.
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Affiliation(s)
- Jie Wang
- Department of Cardiac Care Unit, Yantaishan Hospital, Yantai, Shandong, 264003, China
| | - Haifeng Zhang
- Department of Cardiology, Yantai Yeda Hospital, Yantai, Shangdong, 264006, China
| | - Weiping Wan
- Department of Ultrasound, Yantaishan Hospital, Yantai, Shandong, 264003, China
| | - Haijiao Yang
- Department of Cardiac Care Unit, Yantaishan Hospital, Yantai, Shandong, 264003, China
| | - Jing Zhao
- Department of Critical Care Medicine, Yantaishan Hospital, Yantai, Shandong, 264003, China
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Gao P, Liu Y, Wang X, Feng X, Liu H, Liu S, Huang X, Wu X, Xiong F, Jia X, Hui H, Jiang J, Tian J. Adhesion molecule-targeted magnetic particle imaging nanoprobe for visualization of inflammation in acute lung injury. Eur J Nucl Med Mol Imaging 2024; 51:1233-1245. [PMID: 38095676 DOI: 10.1007/s00259-023-06550-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/26/2023] [Accepted: 11/27/2023] [Indexed: 03/22/2024]
Abstract
PURPOSE Uncontrolled intra-alveolar inflammation is a central pathogenic feature, and its severity translates into a valid prognostic indicator of acute lung injury (ALI). Unfortunately, current clinical imaging approaches are unsuitable for visualizing and quantifying intra-alveolar inflammation. This study aimed to construct a small-sized vascular cell adhesion molecule-1 (VCAM-1)-targeted magnetic particle imaging (MPI) nanoprobe (ESPVPN) to visualize and accurately quantify intra-alveolar inflammation at the molecular level. METHODS ESPVPN was engineered by conjugating a peptide (VHPKQHRGGSK(Cy7)GC) onto a polydopamine-functionalized superparamagnetic iron oxide core. The MPI performance, targeting, and biosafety of the ESPVPN were characterized. VCAM-1 expression in HUVECs and mouse models was evaluated by western blot. The degree of inflammation and distribution of VCAM-1 in the lungs were assessed using histopathology. The expression of pro-inflammatory markers and VCAM-1 in lung tissue lysates was measured using ELISA. After intravenous administration of ESPVPN, MPI and CT imaging were used to analyze the distribution of ESPVPN in the lungs of the LPS-induced ALI models. RESULTS The small-sized (~10 nm) ESPVPN exhibited superior MPI performance compared to commercial MagImaging® and Vivotrax, and ESPVPN had effective targeting and biosafety. VCAM-1 was highly expressed in LPS-induced ALI mice. VCAM-1 expression was positively correlated with the LPS-induced dose (R = 0.9381). The in vivo MPI signal showed positive correlations with both VCAM-1 expression (R = 0.9186) and representative pro-inflammatory markers (MPO, TNF-α, IL-6, IL-8, and IL-1β, R > 0.7). CONCLUSION ESPVPN effectively targeted inflammatory lungs and combined the advantages of MPI quantitative imaging to visualize and evaluate the degree of ALI inflammation.
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Affiliation(s)
- Pengli Gao
- School of Biological Science and Medicine Engineering & School of Engineering Medicine, Beihang University, No. 37, Xueyuan Road, Beijing, 100191, China
- Key Laboratory of Big Data-Based Precision Medicine (Beihang University), Ministry of Industry and Information Technology of the People's Republic of China, No. 37, Xueyuan Road, Beijing, 100191, China
- School of Engineering Medicine, Beihang University, No. 37, Xueyuan Road, Beijing, 100191, China
- CAS Key Laboratory of Molecular Imaging, Key Laboratory of Molecular Imaging, Institute of Automation, Chinese Academy of Sciences, Beijing, 100190, China
| | - Yu Liu
- School of Biological Science and Medicine Engineering & School of Engineering Medicine, Beihang University, No. 37, Xueyuan Road, Beijing, 100191, China
- Key Laboratory of Big Data-Based Precision Medicine (Beihang University), Ministry of Industry and Information Technology of the People's Republic of China, No. 37, Xueyuan Road, Beijing, 100191, China
- School of Engineering Medicine, Beihang University, No. 37, Xueyuan Road, Beijing, 100191, China
- CAS Key Laboratory of Molecular Imaging, Key Laboratory of Molecular Imaging, Institute of Automation, Chinese Academy of Sciences, Beijing, 100190, China
| | - Xiaoli Wang
- School of Medical Imaging, Weifang Medical University, Weifang, 261053, China
| | - Xin Feng
- CAS Key Laboratory of Molecular Imaging, Key Laboratory of Molecular Imaging, Institute of Automation, Chinese Academy of Sciences, Beijing, 100190, China
| | - Heng Liu
- Department of Radiology, PLA Rocket Force Characteristic Medical Center, No. 16 Xinjiekou Outer Street, Beijing, 100088, China
| | - Songlu Liu
- CAS Key Laboratory of Molecular Imaging, Key Laboratory of Molecular Imaging, Institute of Automation, Chinese Academy of Sciences, Beijing, 100190, China
| | - Xiazi Huang
- CAS Key Laboratory of Molecular Imaging, Key Laboratory of Molecular Imaging, Institute of Automation, Chinese Academy of Sciences, Beijing, 100190, China
| | - Xiangjun Wu
- School of Biological Science and Medicine Engineering & School of Engineering Medicine, Beihang University, No. 37, Xueyuan Road, Beijing, 100191, China
- Key Laboratory of Big Data-Based Precision Medicine (Beihang University), Ministry of Industry and Information Technology of the People's Republic of China, No. 37, Xueyuan Road, Beijing, 100191, China
- School of Engineering Medicine, Beihang University, No. 37, Xueyuan Road, Beijing, 100191, China
- CAS Key Laboratory of Molecular Imaging, Key Laboratory of Molecular Imaging, Institute of Automation, Chinese Academy of Sciences, Beijing, 100190, China
| | - Fei Xiong
- School of Biological Science and Medicine Engineering & School of Engineering Medicine, Beihang University, No. 37, Xueyuan Road, Beijing, 100191, China
- Key Laboratory of Big Data-Based Precision Medicine (Beihang University), Ministry of Industry and Information Technology of the People's Republic of China, No. 37, Xueyuan Road, Beijing, 100191, China
- School of Engineering Medicine, Beihang University, No. 37, Xueyuan Road, Beijing, 100191, China
- CAS Key Laboratory of Molecular Imaging, Key Laboratory of Molecular Imaging, Institute of Automation, Chinese Academy of Sciences, Beijing, 100190, China
| | - Xiaohua Jia
- CAS Key Laboratory of Molecular Imaging, Key Laboratory of Molecular Imaging, Institute of Automation, Chinese Academy of Sciences, Beijing, 100190, China
| | - Hui Hui
- CAS Key Laboratory of Molecular Imaging, Key Laboratory of Molecular Imaging, Institute of Automation, Chinese Academy of Sciences, Beijing, 100190, China.
| | - Jingying Jiang
- Key Laboratory of Big Data-Based Precision Medicine (Beihang University), Ministry of Industry and Information Technology of the People's Republic of China, No. 37, Xueyuan Road, Beijing, 100191, China.
- School of Engineering Medicine, Beihang University, No. 37, Xueyuan Road, Beijing, 100191, China.
| | - Jie Tian
- Key Laboratory of Big Data-Based Precision Medicine (Beihang University), Ministry of Industry and Information Technology of the People's Republic of China, No. 37, Xueyuan Road, Beijing, 100191, China.
- School of Engineering Medicine, Beihang University, No. 37, Xueyuan Road, Beijing, 100191, China.
- CAS Key Laboratory of Molecular Imaging, Key Laboratory of Molecular Imaging, Institute of Automation, Chinese Academy of Sciences, Beijing, 100190, China.
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Lee S, Carrow JK, Fraser LA, Yan J, Jeyamogan S, Sambandam Y, Clemons TD, Kolberg-Edelbrock AN, He J, Mathew J, Zhang ZJ, Leventhal JP, Gallon L, Palmer LC, Stupp SI. Single-cell coating with biomimetic extracellular nanofiber matrices. Acta Biomater 2024; 177:50-61. [PMID: 38331132 DOI: 10.1016/j.actbio.2024.02.002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/14/2023] [Revised: 01/17/2024] [Accepted: 02/01/2024] [Indexed: 02/10/2024]
Abstract
Cell therapies offer great promise in the treatment of diseases and tissue regeneration, but their clinical use has many challenges including survival, optimal performance in their intended function, or localization at sites where they are needed for effective outcomes. We report here on a method to coat a biodegradable matrix of biomimetic nanofibers on single cells that could have specific functions ranging from cell signaling to targeting and helping cells survive when used for therapies. The fibers are composed of peptide amphiphile (PA) molecules that self-assemble into supramolecular nanoscale filaments. The PA nanofibers were able to create a mesh-like coating for a wide range of cell lineages with nearly 100 % efficiency, without interrupting the natural cellular phenotype or functions. The targeting abilities of this system were assessed in vitro using human primary regulatory T (hTreg) cells coated with PAs displaying a vascular cell adhesion protein 1 (VCAM-1) targeting motif. This approach provides a biocompatible method for single-cell coating that does not negatively alter cellular phenotype, binding capacity, or immunosuppressive functionality, with potential utility across a broad spectrum of cell therapies. STATEMENT OF SIGNIFICANCE: Cell therapies hold great promise in the treatment of diseases and tissue regeneration, but their clinical use has been limited by cell survival, targeting, and function. We report here a method to coat single cells with a biodegradable matrix of biomimetic nanofibers composed of peptide amphiphile (PA) molecules. The nanofibers were able to coat cells, such as human primary regulatory T cells, with nearly 100 % efficiency, without interrupting the natural cellular phenotype or functions. The approach provides a biocompatible method for single-cell coating that does not negatively alter cellular phenotype, binding capacity, or immunosuppressive functionality, with potential utility across a broad spectrum of cell therapies.
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Affiliation(s)
- Slgirim Lee
- Simpson Querrey Institute for BioNanotechnology, Northwestern University, Chicago, IL 60611, United States
| | - James K Carrow
- Simpson Querrey Institute for BioNanotechnology, Northwestern University, Chicago, IL 60611, United States
| | - Lewis A Fraser
- Simpson Querrey Institute for BioNanotechnology, Northwestern University, Chicago, IL 60611, United States
| | - Jianglong Yan
- Simpson Querrey Institute for BioNanotechnology, Northwestern University, Chicago, IL 60611, United States
| | - Shareni Jeyamogan
- Department of Surgery, Comprehensive Transplant Center, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, United States
| | - Yuvaraj Sambandam
- Department of Surgery, Comprehensive Transplant Center, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, United States
| | - Tristan D Clemons
- Simpson Querrey Institute for BioNanotechnology, Northwestern University, Chicago, IL 60611, United States; Department of Chemistry, Northwestern University, Evanston, IL 60208, United States
| | - Alexandra N Kolberg-Edelbrock
- Simpson Querrey Institute for BioNanotechnology, Northwestern University, Chicago, IL 60611, United States; Department of Biomedical Engineering, Northwestern University, Evanston, IL 60208, United States
| | - Jie He
- Department of Surgery, Comprehensive Transplant Center, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, United States
| | - James Mathew
- Department of Surgery, Comprehensive Transplant Center, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, United States; Department of Microbiology and Immunology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, United States
| | - Zheng Jenny Zhang
- Simpson Querrey Institute for BioNanotechnology, Northwestern University, Chicago, IL 60611, United States; Department of Surgery, Comprehensive Transplant Center, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, United States
| | - Joseph P Leventhal
- Simpson Querrey Institute for BioNanotechnology, Northwestern University, Chicago, IL 60611, United States; Department of Surgery, Comprehensive Transplant Center, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, United States
| | - Lorenzo Gallon
- Simpson Querrey Institute for BioNanotechnology, Northwestern University, Chicago, IL 60611, United States; Department of Medicine, Northwestern University, Chicago, IL 60611, United States
| | - Liam C Palmer
- Simpson Querrey Institute for BioNanotechnology, Northwestern University, Chicago, IL 60611, United States; Department of Chemistry, Northwestern University, Evanston, IL 60208, United States.
| | - Samuel I Stupp
- Simpson Querrey Institute for BioNanotechnology, Northwestern University, Chicago, IL 60611, United States; Department of Chemistry, Northwestern University, Evanston, IL 60208, United States; Department of Biomedical Engineering, Northwestern University, Evanston, IL 60208, United States; Department of Materials Science and Engineering, Northwestern University, Evanston, IL 60208, United States; Department of Medicine, Northwestern University, Chicago, IL 60611, United States.
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Wang J, Lu B, Yin G, Liu L, Yang P, Huang N, Zhao A. Design and Fabrication of Environmentally Responsive Nanoparticles for the Diagnosis and Treatment of Atherosclerosis. ACS Biomater Sci Eng 2024; 10:1190-1206. [PMID: 38343186 DOI: 10.1021/acsbiomaterials.3c01090] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/12/2024]
Abstract
Cardiovascular disease poses a significant threat to human health in today's society. A major contributor to cardiovascular disease is atherosclerosis (AS). The development of plaque in the affected areas involves a complex pathological environment, and the disease progresses rapidly. Nanotechnology, combined with emerging diagnostic and treatment methods, offers the potential for the management of this condition. This paper presents the latest advancements in environment-intelligent responsive controlled-release nanoparticles designed specifically for the pathological environment of AS, which includes characteristics such as low pH, high reactive oxygen species levels, high shear stress, and multienzymes. Additionally, the paper summarizes the applications and features of nanotechnology in interventional therapy for AS, including percutaneous transluminal coronary angioplasty and drug-eluting stents. Furthermore, the application of nanotechnology in the diagnosis of AS shows promising real-time, accurate, and continuous effects. Lastly, the paper explores the future prospects of nanotechnology, highlighting the tremendous potential in the diagnosis and treatment of atherosclerotic diseases, especially with the ongoing development in nano gas, quantum dots, and Metal-Organic Frameworks materials.
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Affiliation(s)
- Jingyue Wang
- Key Lab. for Advanced Technologies of Materials, Ministry of Education, School of Material Science and Engineering, Southwest Jiaotong University, Chengdu 610031, PR China
| | - Bingyang Lu
- Key Lab. for Advanced Technologies of Materials, Ministry of Education, School of Material Science and Engineering, Southwest Jiaotong University, Chengdu 610031, PR China
| | - Ge Yin
- Key Lab. for Advanced Technologies of Materials, Ministry of Education, School of Material Science and Engineering, Southwest Jiaotong University, Chengdu 610031, PR China
| | - Li Liu
- Key Lab. for Advanced Technologies of Materials, Ministry of Education, School of Material Science and Engineering, Southwest Jiaotong University, Chengdu 610031, PR China
| | - Ping Yang
- Key Lab. for Advanced Technologies of Materials, Ministry of Education, School of Material Science and Engineering, Southwest Jiaotong University, Chengdu 610031, PR China
| | - Nan Huang
- Key Lab. for Advanced Technologies of Materials, Ministry of Education, School of Material Science and Engineering, Southwest Jiaotong University, Chengdu 610031, PR China
| | - Ansha Zhao
- Key Lab. for Advanced Technologies of Materials, Ministry of Education, School of Material Science and Engineering, Southwest Jiaotong University, Chengdu 610031, PR China
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10
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Wu X, Liu H, Hu Q, Wang J, Zhang S, Cui W, Shi Y, Bai H, Zhou J, Han L, Li L, Wu Y, Luo J, Wang T, Guo C, Wang Q, Ge S, Qu Y. Astrocyte-Derived Extracellular Vesicular miR-143-3p Dampens Autophagic Degradation of Endothelial Adhesion Molecules and Promotes Neutrophil Transendothelial Migration after Acute Brain Injury. ADVANCED SCIENCE (WEINHEIM, BADEN-WURTTEMBERG, GERMANY) 2024; 11:e2305339. [PMID: 38044319 PMCID: PMC10837358 DOI: 10.1002/advs.202305339] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/02/2023] [Revised: 11/08/2023] [Indexed: 12/05/2023]
Abstract
Pivotal roles of extracellular vesicles (EVs) in the pathogenesis of central nervous system (CNS) disorders including acute brain injury are increasingly acknowledged. Through the analysis of EVs packaged miRNAs in plasma samples from patients with intracerebral hemorrhage (ICH), it is discovered that the level of EVs packaged miR-143-3p (EVs-miR-143-3p) correlates closely with perihematomal edema and neurological outcomes. Further study reveals that, upon ICH, EVs-miR-143-3p is robustly secreted by astrocytes and can shuttle into brain microvascular endothelial cells (BMECs). Heightened levels of miR-143-3p in BMECs induce the up-regulated expression of cell adhesion molecules (CAMs) that bind to circulating neutrophils and facilitate their transendothelial cell migration (TEM) into brain. Mechanism-wise, miR-143-3p directly targets ATP6V1A, resulting in impaired lysosomal hydrolysis ability and reduced autophagic degradation of CAMs. Importantly, a VCAM-1-targeting EVs system to selectively deliver miR-143-3p inhibitor to pathological BMECs is created, which shows satisfactory therapeutic effects in both ICH and traumatic brain injury (TBI) mouse models. In conclusion, the study highlights the causal role of EVs-miR-143-3p in BMECs' dysfunction in acute brain injury and demonstrates a proof of concept that engineered EVs can be devised as a potentially applicable nucleotide drug delivery system for the treatment of CNS disorders.
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Affiliation(s)
- Xun Wu
- Department of NeurosurgeryTangdu Hospitalthe Fourth Military Medical UniversityXi'anShaanxi710038China
| | - Haixiao Liu
- Department of NeurosurgeryTangdu Hospitalthe Fourth Military Medical UniversityXi'anShaanxi710038China
| | - Qing Hu
- Department of NeurosurgeryTangdu Hospitalthe Fourth Military Medical UniversityXi'anShaanxi710038China
| | - Jin Wang
- Department of NeurosurgeryTangdu Hospitalthe Fourth Military Medical UniversityXi'anShaanxi710038China
| | - Shenghao Zhang
- Department of NeurosurgeryTangdu Hospitalthe Fourth Military Medical UniversityXi'anShaanxi710038China
| | - Wenxing Cui
- Department of NeurosurgeryTangdu Hospitalthe Fourth Military Medical UniversityXi'anShaanxi710038China
| | - Yingwu Shi
- Department of NeurosurgeryTangdu Hospitalthe Fourth Military Medical UniversityXi'anShaanxi710038China
| | - Hao Bai
- Department of NeurosurgeryTangdu Hospitalthe Fourth Military Medical UniversityXi'anShaanxi710038China
| | - Jinpeng Zhou
- Department of NeurosurgeryTangdu Hospitalthe Fourth Military Medical UniversityXi'anShaanxi710038China
| | - Liying Han
- Department of NeurosurgeryTangdu Hospitalthe Fourth Military Medical UniversityXi'anShaanxi710038China
| | - Leiyang Li
- Department of NeurosurgeryTangdu Hospitalthe Fourth Military Medical UniversityXi'anShaanxi710038China
| | - Yang Wu
- Department of NeurosurgeryThe Second Hospital of Hebei Medical UniversityShijiazhuangHebei050000China
| | - Jianing Luo
- Department of NeurosurgeryWest Theater General HospitalChengduSichuan610083China
| | - Tinghao Wang
- Department of NeurosurgeryTangdu Hospitalthe Fourth Military Medical UniversityXi'anShaanxi710038China
| | - Chengxuan Guo
- Department of NeurosurgeryTangdu Hospitalthe Fourth Military Medical UniversityXi'anShaanxi710038China
| | - Qiang Wang
- Department of NeurosurgeryTangdu Hospitalthe Fourth Military Medical UniversityXi'anShaanxi710038China
| | - Shunnan Ge
- Department of NeurosurgeryTangdu Hospitalthe Fourth Military Medical UniversityXi'anShaanxi710038China
| | - Yan Qu
- Department of NeurosurgeryTangdu Hospitalthe Fourth Military Medical UniversityXi'anShaanxi710038China
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11
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Pan Q, Chen C, Yang YJ. Top Five Stories of the Cellular Landscape and Therapies of Atherosclerosis: Current Knowledge and Future Perspectives. Curr Med Sci 2024; 44:1-27. [PMID: 38057537 DOI: 10.1007/s11596-023-2818-2] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/25/2023] [Accepted: 10/22/2023] [Indexed: 12/08/2023]
Abstract
Atherosclerosis (AS) is characterized by impairment and apoptosis of endothelial cells, continuous systemic and focal inflammation and dysfunction of vascular smooth muscle cells, which is documented as the traditional cellular paradigm. However, the mechanisms appear much more complicated than we thought since a bulk of studies on efferocytosis, transdifferentiation and novel cell death forms such as ferroptosis, pyroptosis, and extracellular trap were reported. Discovery of novel pathological cellular landscapes provides a large number of therapeutic targets. On the other side, the unsatisfactory therapeutic effects of current treatment with lipid-lowering drugs as the cornerstone also restricts the efforts to reduce global AS burden. Stem cell- or nanoparticle-based strategies spurred a lot of attention due to the attractive therapeutic effects and minimized adverse effects. Given the complexity of pathological changes of AS, attempts to develop an almighty medicine based on single mechanisms could be theoretically challenging. In this review, the top stories in the cellular landscapes during the initiation and progression of AS and the therapies were summarized in an integrated perspective to facilitate efforts to develop a multi-targets strategy and fill the gap between mechanism research and clinical translation. The future challenges and improvements were also discussed.
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Affiliation(s)
- Qi Pan
- State Key Laboratory of Cardiovascular Disease, Department of Cardiology, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, 100037, China
| | - Cheng Chen
- State Key Laboratory of Cardiovascular Disease, Department of Cardiology, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, 100037, China
| | - Yue-Jin Yang
- State Key Laboratory of Cardiovascular Disease, Department of Cardiology, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, 100037, China.
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12
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Park Y, Korzun T, Moses AS, Singh P, Levasseur PR, Demessie AA, Sharma KS, Morgan T, Raitmayr CJ, Avila U, Sabei FY, Taratula OR, Marks DL, Taratula O. Targeted Nanocarriers for Systemic Delivery of IRAK4 Inhibitors to Inflamed Tissues. SMALL (WEINHEIM AN DER BERGSTRASSE, GERMANY) 2024; 20:e2306270. [PMID: 37702136 PMCID: PMC10840923 DOI: 10.1002/smll.202306270] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/24/2023] [Revised: 09/01/2023] [Indexed: 09/14/2023]
Abstract
Persistent and uncontrolled inflammation is the root cause of various debilitating diseases. Given that interleukin-1 receptor-associated kinase 4 (IRAK4) is a critical modulator of inflammation, inhibition of its activity with selective drug molecules (IRAK4 inhibitors) represents a promising therapeutic strategy for inflammatory disorders. To exploit the full potential of this treatment approach, drug carriers for efficient delivery of IRAK4 inhibitors to inflamed tissues are essential. Herein, the first nanoparticle-based platform for the targeted systemic delivery of a clinically tested IRAK4 inhibitor, PF-06650833, with limited aqueous solubility (57 µg mL-1 ) is presented. The developed nanocarriers increase the intrinsic aqueous dispersibility of this IRAK4 inhibitor by 40 times. A targeting peptide on the surface of nanocarriers significantly enhances their accumulation after intravenous injection in inflamed tissues of mice with induced paw edema and ulcerative colitis when compared to non-targeted counterparts. The delivered IRAK4 inhibitor markedly abates inflammation and dramatically suppresses paw edema, mitigates colitis symptoms, and reduces proinflammatory cytokine levels in the affected tissues. Importantly, repeated injections of IRAK4 inhibitor-loaded nanocarriers have no acute toxic effect on major organs of mice. Therefore, the developed nanocarriers have the potential to significantly improve the therapeutic efficacy of IRAK4 inhibitors for different inflammatory diseases.
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Affiliation(s)
- Youngrong Park
- Department of Pharmaceutical Sciences, College of Pharmacy, Oregon State University, 2730 S Moody Avenue, Portland, Oregon, 97201, USA
- Transplantation Research Center, Renal Division, Brigham and Women's Hospital, Harvard Medical School, 221 Longwood Avenue, Boston, Massachusetts, 02115, USA
| | - Tetiana Korzun
- Department of Pharmaceutical Sciences, College of Pharmacy, Oregon State University, 2730 S Moody Avenue, Portland, Oregon, 97201, USA
- Papé Family Pediatric Research Institute, Oregon Health & Science University, 3181 SW Sam Jackson Park Rd, Mail Code L481, Portland, Oregon, 97239, USA
| | - Abraham S Moses
- Department of Pharmaceutical Sciences, College of Pharmacy, Oregon State University, 2730 S Moody Avenue, Portland, Oregon, 97201, USA
| | - Prem Singh
- Department of Pharmaceutical Sciences, College of Pharmacy, Oregon State University, 2730 S Moody Avenue, Portland, Oregon, 97201, USA
| | - Peter R Levasseur
- Papé Family Pediatric Research Institute, Oregon Health & Science University, 3181 SW Sam Jackson Park Rd, Mail Code L481, Portland, Oregon, 97239, USA
| | - Ananiya A Demessie
- Department of Pharmaceutical Sciences, College of Pharmacy, Oregon State University, 2730 S Moody Avenue, Portland, Oregon, 97201, USA
| | - Kongbrailatpam Shitaljit Sharma
- Department of Pharmaceutical Sciences, College of Pharmacy, Oregon State University, 2730 S Moody Avenue, Portland, Oregon, 97201, USA
| | - Terry Morgan
- Department of Pathology and Laboratory Medicine, School of Medicine, Oregon Health & Science University, 3181 SW Sam Jackson Park Road, Portland, Oregon, 97239, USA
| | - Constanze J Raitmayr
- Department of Pharmaceutical Sciences, College of Pharmacy, Oregon State University, 2730 S Moody Avenue, Portland, Oregon, 97201, USA
| | - Uriel Avila
- Department of Pharmaceutical Sciences, College of Pharmacy, Oregon State University, 2730 S Moody Avenue, Portland, Oregon, 97201, USA
| | - Fahad Y Sabei
- Department of Pharmaceutical Sciences, College of Pharmacy, Oregon State University, 2730 S Moody Avenue, Portland, Oregon, 97201, USA
- Department of Pharmaceutics, College of Pharmacy, Jazan University, Al Maarefah Rd, Jazan, 88723, Kingdom of Saudi Arabia
| | - Olena R Taratula
- Department of Pharmaceutical Sciences, College of Pharmacy, Oregon State University, 2730 S Moody Avenue, Portland, Oregon, 97201, USA
| | - Daniel L Marks
- Papé Family Pediatric Research Institute, Oregon Health & Science University, 3181 SW Sam Jackson Park Rd, Mail Code L481, Portland, Oregon, 97239, USA
| | - Oleh Taratula
- Department of Pharmaceutical Sciences, College of Pharmacy, Oregon State University, 2730 S Moody Avenue, Portland, Oregon, 97201, USA
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Tang J, Li T, Xiong X, Yang Q, Su Z, Zheng M, Chen Q. Colchicine delivered by a novel nanoparticle platform alleviates atherosclerosis by targeted inhibition of NF-κB/NLRP3 pathways in inflammatory endothelial cells. J Nanobiotechnology 2023; 21:460. [PMID: 38037046 PMCID: PMC10690998 DOI: 10.1186/s12951-023-02228-z] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2023] [Accepted: 11/20/2023] [Indexed: 12/02/2023] Open
Abstract
Atherosclerosis, a chronic inflammatory disease characterized by arterial plaque formation, is one of the most prominent causes of cardiovascular diseases. However, the current treatments often do not adequately compromise the chronic inflammation-mediated plaque accumulation and the disease progression. Therefore, a new and effective strategy that blocks atherosclerosis-associated inflammation is urgently needed to further reduce the risk. Colchicine, a potent anti-inflammatory medication, has shown great potential in the treatment of atherosclerosis, but its adverse effects have hampered its clinical application. Herein, we developed a novel delivery nanosystem encapsulated with colchicine (VHPK-PLGA@COL), which exhibited improved biosafety and sustained drug release along with the gradual degradation of PLGA and PEG as confirmed both in vitro and in vivo. Surface modification of the nanoparticles with the VHPK peptide ensured its capability to specifically target inflammatory endothelial cells and alleviate atherosclerotic plaque accumulation. In the ApoE - / - atherosclerotic mouse model, both colchicine and VHPK-PLGA@COL treatment significantly decreased the plaque area and enhanced plaque stability by blocking the NF-κB/NLRP3 pathways, while VHPK-PLGA@COL exhibited enhanced therapeutic effects due to its unique ability to target inflammatory endothelial cells without obvious long-term safety concerns. In summary, VHPK-PLGA@COL has the potential to overcome the key translational barriers of colchicine and open new avenues to repurpose this drug for anti-atherosclerotic therapy.
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Affiliation(s)
- Juan Tang
- Department of General Practice, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, 400010, China
- Chongqing Key Laboratory of Ultrasound Molecular Imaging, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, 400010, China
- Department of Endocrinology, The First People's Hospital of Ziyang, Sichuan, 641300, China
| | - Tao Li
- Department of Ophthalmology, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, 400010, China
- Chongqing Key Laboratory of Ultrasound Molecular Imaging, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, 400010, China
- Department of Ophthalmology, The First People's Hospital of Ziyang, Sichuan, 641300, China
| | - Xiaojing Xiong
- Department of General Practice, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, 400010, China
| | - Qiaoyun Yang
- Department of General Practice, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, 400010, China
| | - Zedazhong Su
- Department of General Practice, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, 400010, China
| | - Minming Zheng
- Department of Ophthalmology, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, 400010, China.
| | - Qingwei Chen
- Department of General Practice, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, 400010, China.
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Song JH, Liu MY, Ma YX, Wan QQ, Li J, Diao XO, Niu LN. Inflammation-associated ectopic mineralization. FUNDAMENTAL RESEARCH 2023; 3:1025-1038. [PMID: 38933004 PMCID: PMC11197766 DOI: 10.1016/j.fmre.2022.04.020] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/24/2022] [Revised: 04/06/2022] [Accepted: 04/21/2022] [Indexed: 10/18/2022] Open
Abstract
Ectopic mineralization refers to the deposition of mineralized complexes in the extracellular matrix of soft tissues. Calcific aortic valve disease, vascular calcification, gallstones, kidney stones, and abnormal mineralization in arthritis are common examples of ectopic mineralization. They are debilitating diseases and exhibit excess mortality, disability, and morbidity, which impose on patients with limited social or financial resources. Recent recognition that inflammation plays an important role in ectopic mineralization has attracted the attention of scientists from different research fields. In the present review, we summarize the origin of inflammation in ectopic mineralization and different channels whereby inflammation drives the initiation and progression of ectopic mineralization. The current knowledge of inflammatory milieu in pathological mineralization is reviewed, including how immune cells, pro-inflammatory mediators, and osteogenic signaling pathways induce the osteogenic transition of connective tissue cells, providing nucleating sites and assembly of aberrant minerals. Advances in the understanding of the underlying mechanisms involved in inflammatory-mediated ectopic mineralization enable novel strategies to be developed that may lead to the resolution of these enervating conditions.
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Affiliation(s)
| | | | | | - Qian-Qian Wan
- State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration & National Clinical Research Centre for Oral Diseases & Shaanxi Key Laboratory of Stomatology, Department of Prosthodontics, School of Stomatology, The Fourth Military Medical University, Xi'an, Shaanxi 710032, China
| | - Jing Li
- State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration & National Clinical Research Centre for Oral Diseases & Shaanxi Key Laboratory of Stomatology, Department of Prosthodontics, School of Stomatology, The Fourth Military Medical University, Xi'an, Shaanxi 710032, China
| | - Xiao-Ou Diao
- State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration & National Clinical Research Centre for Oral Diseases & Shaanxi Key Laboratory of Stomatology, Department of Prosthodontics, School of Stomatology, The Fourth Military Medical University, Xi'an, Shaanxi 710032, China
| | - Li-Na Niu
- State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration & National Clinical Research Centre for Oral Diseases & Shaanxi Key Laboratory of Stomatology, Department of Prosthodontics, School of Stomatology, The Fourth Military Medical University, Xi'an, Shaanxi 710032, China
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15
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Setia A, Mehata AK, Priya V, Pawde DM, Jain D, Mahto SK, Muthu MS. Current Advances in Nanotheranostics for Molecular Imaging and Therapy of Cardiovascular Disorders. Mol Pharm 2023; 20:4922-4941. [PMID: 37699355 DOI: 10.1021/acs.molpharmaceut.3c00582] [Citation(s) in RCA: 10] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 09/14/2023]
Abstract
Cardiovascular diseases (CVDs) refer to a collection of conditions characterized by abnormalities in the cardiovascular system. They are a global problem and one of the leading causes of mortality and disability. Nanotheranostics implies to the combination of diagnostic and therapeutic capabilities inside a single nanoscale platform that has allowed for significant advancement in cardiovascular diagnosis and therapy. These advancements are being developed to improve imaging capabilities, introduce personalized therapies, and boost cardiovascular disease patient treatment outcomes. Significant progress has been achieved in the integration of imaging and therapeutic capabilities within nanocarriers. In the case of cardiovascular disease, nanoparticles provide targeted delivery of therapeutics, genetic material, photothermal, and imaging agents. Directing and monitoring the movement of these therapeutic nanoparticles may be done with pinpoint accuracy by using imaging modalities such as cardiovascular magnetic resonance (CMR), computed tomography (CT), positron emission tomography (PET), photoacoustic/ultrasound, and fluorescence imaging. Recently, there has been an increasing demand of noninvasive for multimodal nanotheranostic platforms. In these platforms, various imaging technologies such as optical and magnetic resonance are integrated into a single nanoparticle. This platform helps in acquiring more accurate descriptions of cardiovascular diseases and provides clues for accurate diagnosis. Advances in surface functionalization methods have strengthened the potential application of nanotheranostics in cardiovascular diagnosis and therapy. In this Review, we have covered the potential impact of nanomedicine on CVDs. Additionally, we have discussed the recently developed various nanoparticles for CVDs imaging. Moreover, advancements in the CMR, CT, PET, ultrasound, and photoacoustic imaging for the CVDs have been discussed. We have limited our discussion to nanomaterials based clinical trials for CVDs and their patents.
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Affiliation(s)
- Aseem Setia
- Department of Pharmaceutical Engineering and Technology, Indian Institute of Technology (BHU), Varanasi, Uttar Pradesh 221005, India
| | - Abhishesh Kumar Mehata
- Department of Pharmaceutical Engineering and Technology, Indian Institute of Technology (BHU), Varanasi, Uttar Pradesh 221005, India
| | - Vishnu Priya
- Department of Pharmaceutical Engineering and Technology, Indian Institute of Technology (BHU), Varanasi, Uttar Pradesh 221005, India
| | - Datta Maroti Pawde
- School of Pharmacy & Technology Management, SVKM's Narsee Monjee Institute of Management Studies (NMIMS) Deemed-to-be University, Shirpur, Dhule, Maharashtra 425405, India
| | - Dharmendra Jain
- Department of Cardiology, Institute of Medical Sciences, Banaras Hindu University, Varanasi, Uttar Pradesh 221005, India
| | - Sanjeev Kumar Mahto
- School of Biomedical Engineering, Indian Institute of Technology (BHU), Varanasi, Uttar Pradesh 221005, India
| | - Madaswamy S Muthu
- Department of Pharmaceutical Engineering and Technology, Indian Institute of Technology (BHU), Varanasi, Uttar Pradesh 221005, India
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Li Y, Wang J, Xie J. Biomimetic nanoparticles targeting atherosclerosis for diagnosis and therapy. SMART MEDICINE 2023; 2:e20230015. [PMID: 39188346 PMCID: PMC11236035 DOI: 10.1002/smmd.20230015] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 04/07/2023] [Accepted: 05/28/2023] [Indexed: 08/28/2024]
Abstract
Atherosclerosis is a typical chronic inflammatory vascular disease that seriously endangers human health. At present, oral lipid-lowering or anti-inflammatory drugs are clinically used to inhibit the development of atherosclerosis. However, traditional oral drug treatments have problems such as low utilization, slow response, and serious side effects. Traditional nanodrug delivery systems are difficult to interactively recognize by normal biological organisms, and it is difficult to target the delivery of drugs to target lesions. Therefore, building a biomimetic nanodrug delivery system with targeted drug delivery based on the pathological characteristics of atherosclerosis is the key to achieving efficient and safe treatment of atherosclerosis. In this review, various nanodrug delivery systems that can target atherosclerosis are summarized and discussed. In addition, the future prospects and challenges of its clinical translation are also discussed.
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Affiliation(s)
- Yuyu Li
- Department of CardiologyNational Cardiovascular Disease Regional Center for Anhuithe First Affiliated Hospital of Anhui Medical UniversityHefeiChina
- Key Laboratory of Remodeling‐Related Cardiovascular Diseases, Ministry of Education, Beijing Collaborative Innovation Centre for Cardiovascular Disorders, Beijing Anzhen Hospital, Capital Medical UniversityBeijingChina
- Beijing Institute of Heart, Lung, and Blood Vessel DiseasesBeijing Anzhen Hospital Affiliated to Capital Medical UniversityBeijingChina
| | - Jifang Wang
- Department of CardiologyNational Cardiovascular Disease Regional Center for Anhuithe First Affiliated Hospital of Anhui Medical UniversityHefeiChina
- Department of CardiologyDrum Tower HospitalMedical School of Nanjing UniversityNanjingChina
| | - Jun Xie
- Department of CardiologyNational Cardiovascular Disease Regional Center for Anhuithe First Affiliated Hospital of Anhui Medical UniversityHefeiChina
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17
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Uzhytchak M, Smolková B, Lunova M, Frtús A, Jirsa M, Dejneka A, Lunov O. Lysosomal nanotoxicity: Impact of nanomedicines on lysosomal function. Adv Drug Deliv Rev 2023; 197:114828. [PMID: 37075952 DOI: 10.1016/j.addr.2023.114828] [Citation(s) in RCA: 22] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/12/2021] [Revised: 03/28/2023] [Accepted: 04/12/2023] [Indexed: 04/21/2023]
Abstract
Although several nanomedicines got clinical approval over the past two decades, the clinical translation rate is relatively small so far. There are many post-surveillance withdrawals of nanomedicines caused by various safety issues. For successful clinical advancement of nanotechnology, it is of unmet need to realize cellular and molecular foundation of nanotoxicity. Current data suggest that lysosomal dysfunction caused by nanoparticles is emerging as the most common intracellular trigger of nanotoxicity. This review analyzes prospect mechanisms of lysosomal dysfunction-mediated toxicity induced by nanoparticles. We summarized and critically assessed adverse drug reactions of current clinically approved nanomedicines. Importantly, we show that physicochemical properties have great impact on nanoparticles interaction with cells, excretion route and kinetics, and subsequently on toxicity. We analyzed literature on adverse reactions of current nanomedicines and hypothesized that adverse reactions might be linked with lysosomal dysfunction caused by nanomedicines. Finally, from our analysis it becomes clear that it is unjustifiable to generalize safety and toxicity of nanoparticles, since different particles possess distinct toxicological properties. We propose that the biological mechanism of the disease progression and treatment should be central in the optimization of nanoparticle design.
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Affiliation(s)
- Mariia Uzhytchak
- Institute of Physics of the Czech Academy of Sciences, 18221 Prague, Czech Republic
| | - Barbora Smolková
- Institute of Physics of the Czech Academy of Sciences, 18221 Prague, Czech Republic
| | - Mariia Lunova
- Institute of Physics of the Czech Academy of Sciences, 18221 Prague, Czech Republic; Institute for Clinical & Experimental Medicine (IKEM), 14021 Prague, Czech Republic
| | - Adam Frtús
- Institute of Physics of the Czech Academy of Sciences, 18221 Prague, Czech Republic
| | - Milan Jirsa
- Institute for Clinical & Experimental Medicine (IKEM), 14021 Prague, Czech Republic
| | - Alexandr Dejneka
- Institute of Physics of the Czech Academy of Sciences, 18221 Prague, Czech Republic
| | - Oleg Lunov
- Institute of Physics of the Czech Academy of Sciences, 18221 Prague, Czech Republic.
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18
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Solidum JGN, Ceriales JA, Ong EP, Ornos EDB, Relador RJL, Quebral EPB, Lapeña JFF, Tantengco OAG, Lee KY. Nanomedicine and nanoparticle-based delivery systems in plastic and reconstructive surgery. Maxillofac Plast Reconstr Surg 2023; 45:15. [PMID: 36995508 PMCID: PMC10060935 DOI: 10.1186/s40902-023-00383-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/29/2022] [Accepted: 03/06/2023] [Indexed: 03/31/2023] Open
Abstract
BACKGROUND Nanotechnology and nanomedicine are rising novel fields in plastic and reconstructive surgery (PRS). The use of nanomaterials often goes with regenerative medicine. Due to their nanoscale, these materials stimulate repair at the cellular and molecular levels. Nanomaterials may be placed as components of nanocomposite polymers allowing enhancement of overall biochemical and biomechanical properties with improved scaffold properties, cellular attachment, and tissue regeneration. They may also be formulated as nanoparticle-based delivery systems for controlled release of signal factors or antimicrobials, for example. However, more studies on nanoparticle-based delivery systems still need to be done in this field. Nanomaterials are also used as frameworks for nerves, tendons, and other soft tissues. MAIN BODY In this mini-review, we focus on nanoparticle-based delivery systems and nanoparticles targeting cells for response and regeneration in PRS. Specifically, we investigate their roles in various tissue regeneration, skin and wound healing, and infection control. Cell surface-targeted, controlled-release, and inorganic nanoparticle formulations with inherent biological properties have enabled enhanced wound healing, tumor visualization/imaging, tissue viability, and decreased infection, and graft/transplantation rejection through immunosuppression. CONCLUSIONS Nanomedicine is also now being applied with electronics, theranostics, and advanced bioengineering technologies. Overall, it is a promising field that can improve patient clinical outcomes in PRS.
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Affiliation(s)
- Jea Giezl N Solidum
- MD-PhD (Molecular Medicine) Program, College of Medicine, University of the Philippines Manila, Ermita, Manila, 1000, Philippines
| | - Jeremy A Ceriales
- MD-PhD (Molecular Medicine) Program, College of Medicine, University of the Philippines Manila, Ermita, Manila, 1000, Philippines
| | - Erika P Ong
- College of Medicine, University of the Philippines Manila, Ermita, Manila, 1000, Philippines
| | - Eric David B Ornos
- MD-PhD (Molecular Medicine) Program, College of Medicine, University of the Philippines Manila, Ermita, Manila, 1000, Philippines
| | - Ruth Joy L Relador
- MD-PhD (Molecular Medicine) Program, College of Medicine, University of the Philippines Manila, Ermita, Manila, 1000, Philippines
| | - Elgin Paul B Quebral
- MD-PhD (Molecular Medicine) Program, College of Medicine, University of the Philippines Manila, Ermita, Manila, 1000, Philippines
| | - Jose Florencio F Lapeña
- Department of Otolaryngology - Head and Neck Surgery, Section of Craniomaxillofacial Plastic and Restorative Surgery, College of Medicine - Philippine General Hospital, University of the Philippines Manila, Ermita, Manila, 1000, Philippines
| | - Ourlad Alzeus G Tantengco
- Department of Physiology, College of Medicine, University of the Philippines Manila, Ermita, Manila, 1000, Philippines.
- Department of Biology, College of Science, De La Salle University, Manila, 1004, Philippines.
| | - Ka Yiu Lee
- Swedish Winter Sports Research Centre, Department of Health Sciences, Mid Sweden University, Östersund, Sweden.
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19
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Pan J, Chen Y, Hu Y, Wang H, Chen W, Zhou Q. Molecular imaging research in atherosclerosis: A 23-year scientometric and visual analysis. Front Bioeng Biotechnol 2023; 11:1152067. [PMID: 37122864 PMCID: PMC10133554 DOI: 10.3389/fbioe.2023.1152067] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/17/2023] [Accepted: 04/06/2023] [Indexed: 05/02/2023] Open
Abstract
Background: Cardiovascular and cerebrovascular diseases are major global health problems, and the main cause is atherosclerosis. Recently, molecular imaging has been widely employed in the diagnosis and therapeutic applications of a variety of diseases, including atherosclerosis. Substantive facts have announced that molecular imaging has broad prospects in the early diagnosis and targeted treatment of atherosclerosis. Objective: We conducted a scientometric analysis of the scientific publications over the past 23 years on molecular imaging research in atherosclerosis, so as to identify the key progress, hotspots, and emerging trends. Methods: Original research and reviews regarding molecular imaging in atherosclerosis were retrieved from the Web of Science Core Collection database. Microsoft Excel 2021 was used to analyze the main findings. CiteSpace, VOSviewer, and a scientometric online platform were used to perform visualization analysis of the co-citation of journals and references, co-occurrence of keywords, and collaboration between countries/regions, institutions, and authors. Results: A total of 1755 publications were finally included, which were published by 795 authors in 443 institutions from 59 countries/regions. The United States was the top country in terms of the number and centrality of publications in this domain, with 810 papers and a centrality of 0.38, and Harvard University published the largest number of articles (182). Fayad, ZA was the most productive author, with 73 papers, while LIBBY P had the most co-citations (493). CIRCULATION was the top co-cited journal with a frequency of 1,411, followed by ARTERIOSCL THROM VAS (1,128). The co-citation references analysis identified eight clusters with a well-structured network (Q = 0.6439) and highly convincing clustering (S = 0.8865). All the studies calculated by keyword co-occurrence were divided into five clusters: "nanoparticle," "magnetic resonance imaging," "inflammation," "positron emission tomography," and "ultrasonography". Hot topics mainly focused on cardiovascular disease, contrast media, macrophage, vulnerable plaque, and microbubbles. Sodium fluoride ⁃PET, targeted drug delivery, OCT, photoacoustic imaging, ROS, and oxidative stress were identified as the potential trends. Conclusion: Molecular imaging research in atherosclerosis has attracted extensive attention in academia, while the challenges of clinical transformation faced in this field have been described in this review. The findings of the present research can inform funding agencies and researchers toward future directions.
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20
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Choi KA, Kim JH, Ryu K, Kaushik N. Current Nanomedicine for Targeted Vascular Disease Treatment: Trends and Perspectives. Int J Mol Sci 2022; 23:12397. [PMID: 36293254 PMCID: PMC9604340 DOI: 10.3390/ijms232012397] [Citation(s) in RCA: 14] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/04/2022] [Revised: 10/04/2022] [Accepted: 10/14/2022] [Indexed: 12/19/2022] Open
Abstract
Nanotechnology has been developed to deliver cargos effectively to the vascular system. Nanomedicine is a novel and effective approach for targeted vascular disease treatment including atherosclerosis, coronary artery disease, strokes, peripheral arterial disease, and cancer. It has been well known for some time that vascular disease patients have a higher cancer risk than the general population. During atherogenesis, the endothelial cells are activated to increase the expression of adhesion molecules such as Intercellular Adhesion Molecule 1 (ICAM-1), Vascular cell adhesion protein 1 (VCAM-1), E-selectin, and P-selectin. This biological activation of endothelial cells gives a targetability clue for nanoparticle strategies. Nanoparticle formation has a passive targeting pathway due to the increased adhesion molecule expression on the cell surface as well as increased cell activation. In addition, the VCAM-1-targeting peptide has been widely used to target the inflamed endothelial cells. Biomimetic nanoparticles using platelet and leukocyte membrane fragment strategies have been promising techniques for targeted vascular disease treatment. Cyclodextrin, a natural oligosaccharide with a hydrophobic cavity, increase the solubility of cholesterol crystals at the atherosclerotic plaque site and has been used to deliver the hydrophobic drug statin as a therapeutic in a targeted manner. In summary, nanoparticles decorated with various targeting molecules will be an effective and promising strategy for targeted vascular disease treatment.
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Affiliation(s)
- Kyung-A Choi
- National Institute of Medical Welfare, Kangnam University, Yongin 16979, Korea
| | - June Hyun Kim
- Department of Biotechnology, The University of Suwon, Suwon 18323, Korea
| | - Kitae Ryu
- Department of Biotechnology, The University of Suwon, Suwon 18323, Korea
| | - Neha Kaushik
- Department of Biotechnology, The University of Suwon, Suwon 18323, Korea
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21
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Li X, Wu M, Li J, Guo Q, Zhao Y, Zhang X. Advanced targeted nanomedicines for vulnerable atherosclerosis plaque imaging and their potential clinical implications. Front Pharmacol 2022; 13:906512. [PMID: 36313319 PMCID: PMC9606597 DOI: 10.3389/fphar.2022.906512] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/28/2022] [Accepted: 09/20/2022] [Indexed: 12/24/2022] Open
Abstract
Atherosclerosis plaques caused by cerebrovascular and coronary artery disease have been the leading cause of death and morbidity worldwide. Precise assessment of the degree of atherosclerotic plaque is critical for predicting the risk of atherosclerosis plaques and monitoring postinterventional outcomes. However, traditional imaging techniques to predict cardiocerebrovascular events mainly depend on quantifying the percentage reduction in luminal diameter, which would immensely underestimate non-stenotic high-risk plaque. Identifying the degree of atherosclerosis plaques still remains highly limited. vNanomedicine-based imaging techniques present unique advantages over conventional techniques due to the superior properties intrinsic to nanoscope, which possess enormous potential for characterization and detection of the features of atherosclerosis plaque vulnerability. Here, we review recent advancements in the development of targeted nanomedicine-based approaches and their applications to atherosclerosis plaque imaging and risk stratification. Finally, the challenges and opportunities regarding the future development and clinical translation of the targeted nanomedicine in related fields are discussed.
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Affiliation(s)
| | | | | | | | | | - Xuening Zhang
- Department of Radiology, Tianjin Medical University Second Hospital, Tianjin, China
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22
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Li X, Qi H, Cui W, Wang Z, Fu X, Li T, Ma H, Yang Y, Yu T. Recent advances in targeted delivery of non-coding RNA-based therapeutics for atherosclerosis. Mol Ther 2022; 30:3118-3132. [PMID: 35918894 PMCID: PMC9552813 DOI: 10.1016/j.ymthe.2022.07.018] [Citation(s) in RCA: 29] [Impact Index Per Article: 9.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/20/2022] [Revised: 07/28/2022] [Accepted: 07/30/2022] [Indexed: 10/16/2022] Open
Abstract
Cardiovascular disease (CVD) has overtaken infectious illnesses as the leading cause of mortality and disability worldwide. The pathology that underpins CVD is atherosclerosis, characterized by chronic inflammation caused by the accumulation of plaques in the arteries. As our knowledge about the microenvironment of blood vessel walls deepens, there is an opportunity to fine-tune treatments to target the mechanisms driving atherosclerosis more directly. The application of non-coding RNAs (ncRNAs) as biomarkers or intervention targets is increasing. Although these ncRNAs play an important role in driving atherosclerosis and vascular dysfunction, the cellular and extracellular environments pose a challenge for targeted transmission and therapeutic regulation of ncRNAs. Specificity, delivery, and tolerance have hampered the clinical translation of ncRNA-based therapeutics. Nanomedicine is an emerging field that uses nanotechnology for targeted drug delivery and advanced imaging. Recently, nanoscale carriers have shown promising results and have introduced new possibilities for nucleic acid targeted drug delivery, particularly for atherosclerosis. In this review, we discuss the latest developments in nanoparticles to aid ncRNA-based drug development, particularly miRNA, and we analyze the current challenges in ncRNA targeted delivery. In particular, we highlight the emergence of various kinds of nanotherapeutic approaches based on ncRNAs, which can improve treatment options for atherosclerosis.
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Affiliation(s)
- Xiaoxin Li
- Center for Regenerative Medicine, Institute for Translational Medicine, The Affiliated Hospital of Qingdao University, No. 38 Dengzhou Road, Qingdao 266021, People's Republic of China
| | - Hongzhao Qi
- Center for Regenerative Medicine, Institute for Translational Medicine, The Affiliated Hospital of Qingdao University, No. 38 Dengzhou Road, Qingdao 266021, People's Republic of China
| | - Weigang Cui
- Department of Cardiology, People's Hospital of Rizhao, No. 126 Taian Road, Rizhao 276827, People's Republic of China
| | - Zhibin Wang
- Department of Cardiac Ultrasound, The Affiliated Hospital of Qingdao University, No.16 Jiangsu Road, Qingdao 266000, China
| | - Xiuxiu Fu
- Department of Cardiac Ultrasound, The Affiliated Hospital of Qingdao University, No.16 Jiangsu Road, Qingdao 266000, China
| | - Tianxiang Li
- Center for Regenerative Medicine, Institute for Translational Medicine, The Affiliated Hospital of Qingdao University, No. 38 Dengzhou Road, Qingdao 266021, People's Republic of China
| | - Huibo Ma
- Department of Vascular Surgery, The Affiliated Hospital of Qingdao University, Qingdao, China
| | - Yanyan Yang
- Department of Immunology, School of Basic Medicine, Qingdao University, Qingdao 266021, People's Republic of China.
| | - Tao Yu
- Center for Regenerative Medicine, Institute for Translational Medicine, The Affiliated Hospital of Qingdao University, No. 38 Dengzhou Road, Qingdao 266021, People's Republic of China; Department of Cardiac Ultrasound, The Affiliated Hospital of Qingdao University, No.16 Jiangsu Road, Qingdao 266000, China.
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23
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Hetherington I, Totary-Jain H. Anti-atherosclerotic therapies: Milestones, challenges, and emerging innovations. Mol Ther 2022; 30:3106-3117. [PMID: 36065464 PMCID: PMC9552812 DOI: 10.1016/j.ymthe.2022.08.024] [Citation(s) in RCA: 49] [Impact Index Per Article: 16.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/24/2022] [Revised: 08/26/2022] [Accepted: 08/30/2022] [Indexed: 11/22/2022] Open
Abstract
Atherosclerosis is the main underlying pathology for many cardiovascular diseases (CVDs), which are the leading cause of death globally and represent a serious health crisis. Atherosclerosis is a chronic condition that can lead to myocardial infarction, ischemic cardiomyopathy, stroke, and peripheral arterial disease. Elevated plasma lipids, hypertension, and high glucose are the major risk factors for developing atherosclerotic plaques. To date, most pharmacological therapies aim to control these risk factors, but they do not target the plaque-causing cells themselves. In patients with acute coronary syndromes, surgical revascularization with percutaneous coronary intervention has greatly reduced mortality rates. However, stent thrombosis and neo-atherosclerosis have emerged as major safety concerns of drug eluting stents due to delayed re-endothelialization. This review summarizes the major milestones, strengths, and limitations of current anti-atherosclerotic therapies. It provides an overview of the recent discoveries and emerging game-changing technologies in the fields of nanomedicine, mRNA therapeutics, and gene editing that have the potential to revolutionize CVD clinical practice by steering it toward precision medicine.
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Affiliation(s)
- Isabella Hetherington
- Department of Molecular Pharmacology and Physiology, Morsani College of Medicine, University of South Florida, 12901 Bruce B. Downs Blvd., MDC08, 2170, Tampa, FL 33612, USA
| | - Hana Totary-Jain
- Department of Molecular Pharmacology and Physiology, Morsani College of Medicine, University of South Florida, 12901 Bruce B. Downs Blvd., MDC08, 2170, Tampa, FL 33612, USA.
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24
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Scavenger receptor-targeted plaque delivery of microRNA-coated nanoparticles for alleviating atherosclerosis. Proc Natl Acad Sci U S A 2022; 119:e2201443119. [PMID: 36122215 PMCID: PMC9522431 DOI: 10.1073/pnas.2201443119] [Citation(s) in RCA: 20] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/18/2022] Open
Abstract
Atherosclerosis treatments by gene regulation are garnering attention, yet delivery of gene cargoes to atherosclerotic plaques remains inefficient. Here, we demonstrate that assembly of therapeutic oligonucleotides into a three-dimensional spherical nucleic acid nanostructure improves their systemic delivery to the plaque and the treatment of atherosclerosis. This noncationic nanoparticle contains a shell of microRNA-146a oligonucleotides, which regulate the NF-κB pathway, for achieving transfection-free cellular entry. Upon an intravenous injection into apolipoprotein E knockout mice fed with a high-cholesterol diet, this nanoparticle naturally targets class A scavenger receptor on plaque macrophages and endothelial cells, contributing to elevated delivery to the plaques (∼1.2% of the injected dose). Repeated injections of the nanoparticle modulate genes related to immune response and vascular inflammation, leading to reduced and stabilized plaques but without inducing severe toxicity. Our nanoparticle offers a safe and effective treatment of atherosclerosis and reveals the promise of nucleic acid nanotechnology for cardiovascular disease.
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25
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Li W, Gonzalez KM, Chung J, Kim M, Lu J. Surface-modified nanotherapeutics targeting atherosclerosis. Biomater Sci 2022; 10:5459-5471. [PMID: 35980230 PMCID: PMC9529904 DOI: 10.1039/d2bm00660j] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022]
Abstract
Atherosclerosis is a chronic and metabolic-related disease that is a serious threat to human health. Currently available diagnostic and therapeutic measures for atherosclerosis lack adequate efficiency which requires promising alternative approaches. Nanotechnology-based nano-delivery systems allow for new perspectives for atherosclerosis therapy. Surface-modified nanoparticles could achieve highly effective therapeutic effects by binding to specific receptors that are abnormally overexpressed in atherosclerosis, with less adverse effects on non-target tissues. The main purpose of this review is to summarize the research progress and design ideas to target atherosclerosis using a variety of ligand-modified nanoparticle systems, discuss the shortcomings of current vector design, and look at future development directions. We hope that this review will provide novel research strategies for the design and development of nanotherapeutics targeting atherosclerosis.
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Affiliation(s)
- Wenpan Li
- Skaggs Pharmaceutical Sciences Center, Department of Pharmacology & Toxicology, R. Ken Coit College of Pharmacy, The University of Arizona, Tucson, Arizona, 85721, USA.
| | - Karina Marie Gonzalez
- Skaggs Pharmaceutical Sciences Center, Department of Pharmacology & Toxicology, R. Ken Coit College of Pharmacy, The University of Arizona, Tucson, Arizona, 85721, USA.
| | - Jinha Chung
- Skaggs Pharmaceutical Sciences Center, Department of Pharmacology & Toxicology, R. Ken Coit College of Pharmacy, The University of Arizona, Tucson, Arizona, 85721, USA.
| | - Minhyeok Kim
- Skaggs Pharmaceutical Sciences Center, Department of Pharmacology & Toxicology, R. Ken Coit College of Pharmacy, The University of Arizona, Tucson, Arizona, 85721, USA.
| | - Jianqin Lu
- Skaggs Pharmaceutical Sciences Center, Department of Pharmacology & Toxicology, R. Ken Coit College of Pharmacy, The University of Arizona, Tucson, Arizona, 85721, USA.
- NCI-designated University of Arizona Comprehensive Cancer Center, Tucson, Arizona, 85721, USA
- BIO5 Institute, The University of Arizona, Tucson, Arizona, 85721, USA
- Southwest Environmental Health Sciences Center, The University of Arizona, Tucson, 85721, USA
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26
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Shava B, Ayodeji FD, Rahdar A, Iqbal HM, Bilal M. Magnetic nanoparticles-based systems for multifaceted biomedical applications. J Drug Deliv Sci Technol 2022; 74:103616. [DOI: 10.1016/j.jddst.2022.103616] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022]
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27
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Vascular Cell Adhesion Molecule 1-Mediated Targeting of Human Hematopoietic Stem Cells to Bone Marrow Is Effective in Conferring Regeneration and Survival in Lethally Irradiated Mice. Transplant Cell Ther 2022; 28:667.e1-667.e10. [DOI: 10.1016/j.jtct.2022.07.012] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/15/2022] [Revised: 07/06/2022] [Accepted: 07/11/2022] [Indexed: 11/19/2022]
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28
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Huang C, Huang W, Zhang L, Zhang C, Zhou C, Wei W, Li Y, Zhou Q, Chen W, Tang Y. Targeting Peptide, Fluorescent Reagent Modified Magnetic Liposomes Coated with Rapamycin Target Early Atherosclerotic Plaque and Therapy. Pharmaceutics 2022; 14:1083. [PMID: 35631669 PMCID: PMC9146689 DOI: 10.3390/pharmaceutics14051083] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/05/2022] [Revised: 05/09/2022] [Accepted: 05/16/2022] [Indexed: 11/26/2022] Open
Abstract
Atherosclerosis is the leading cause of global morbidity and mortality. Its therapy requires research in several areas, such as diagnosis of early arteriosclerosis, improvement of the pharmacokinetics and bioavailability of rapamycin as its therapeutic agents. Here, we used the targeting peptide VHPKQHR (VHP) (or fluorescent reagent) to modify the phospholipid molecules to target vascular cell adhesion molecule-1 (VCAM-1) and loaded ultrasmall paramagnetic iron oxide (USPIO/Fe3O4) plus rapamycin (Rap) to Rap/Fe3O4@VHP-Lipo (VHPKQHR-modified magnetic liposomes coated with Rap). This nanoparticle can be used for both the diagnosis and therapy of early atherosclerosis. We designed both an ex vivo system with mouse aortic endothelial cells (MAECs) and an in vivo system with ApoE knockout mice to test the labeling and delivering potential of Rap/Fe3O4@VHP-Lipo with fluorescent microscopy, flow cytometry and MRI. Our results of MRI imaging and fluorescence imaging showed that the T2 relaxation time of the Rap/Fe3O4@VHP-Lipo group was reduced by 2.7 times and 1.5 times, and the fluorescence intensity increased by 3.4 times and 2.5 times, respectively, compared with the normal saline group and the control liposome treatment group. It showed that Rap/Fe3O4@VHP-Lipo realized the diagnosis of early AS. Additionally, our results showed that, compared with the normal saline and control liposomes treatment group, the aortic fluorescence intensity of the Rap/Fe3O4@VHP-Lipo treatment group was significantly weaker, and the T2 relaxation time was prolonged by 8.9 times and 2.0 times, indicating that the targeted diagnostic agent detected the least plaques in the Rap/Fe3O4@VHP-Lipo treatment group. Based on our results, the synthesized theragnostic Rap/Fe3O4@VHP-Lipo serves as a great label for both MRI and fluorescence bimodal imaging of atherosclerosis. It also has therapeutic effects for the early treatment of atherosclerosis, and it has great potential for early diagnosis and can achieve the same level of therapy with a lower dose of Rap.
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Affiliation(s)
- Chen Huang
- Department of Minimally Invasive Interventional Radiology, Guangzhou Panyu Central Hospital, Guangzhou 511400, China;
| | - Wentao Huang
- MOE Key Laboratory of Laser Life Science & Institute of Laser Life Science, College of Biophotonics, South China Normal University, Guangzhou 510631, China; (W.H.); (L.Z.); (C.Z.); (W.C.)
- Guangdong Provincial Key Laboratory of Laser Life Science, College of Biophotonics, South China Normal University, Guangzhou 510631, China
- Institute for Brain Research and Rehabilitation, South China Normal University, Guangzhou 510631, China
| | - Lifen Zhang
- MOE Key Laboratory of Laser Life Science & Institute of Laser Life Science, College of Biophotonics, South China Normal University, Guangzhou 510631, China; (W.H.); (L.Z.); (C.Z.); (W.C.)
- Guangdong Provincial Key Laboratory of Laser Life Science, College of Biophotonics, South China Normal University, Guangzhou 510631, China
- Institute for Brain Research and Rehabilitation, South China Normal University, Guangzhou 510631, China
| | - Chunyu Zhang
- MOE Key Laboratory of Laser Life Science & Institute of Laser Life Science, College of Biophotonics, South China Normal University, Guangzhou 510631, China; (W.H.); (L.Z.); (C.Z.); (W.C.)
- Guangdong Provincial Key Laboratory of Laser Life Science, College of Biophotonics, South China Normal University, Guangzhou 510631, China
- Institute for Brain Research and Rehabilitation, South China Normal University, Guangzhou 510631, China
| | - Chengqian Zhou
- Neuroscience Laboratory, Hugo Moser Research Institute at Kennedy Krieger, Baltimore, MD 21205, USA;
| | - Wei Wei
- Institution of Guang Dong Cord Blood Bank, Guangzhou 510700, China; (W.W.); (Y.L.)
| | - Yongsheng Li
- Institution of Guang Dong Cord Blood Bank, Guangzhou 510700, China; (W.W.); (Y.L.)
| | - Quan Zhou
- Department of Radiology, The Third Affiliated Hospital of Southern Medical University, Guangzhou 510630, China
| | - Wenli Chen
- MOE Key Laboratory of Laser Life Science & Institute of Laser Life Science, College of Biophotonics, South China Normal University, Guangzhou 510631, China; (W.H.); (L.Z.); (C.Z.); (W.C.)
- Guangdong Provincial Key Laboratory of Laser Life Science, College of Biophotonics, South China Normal University, Guangzhou 510631, China
- Institute for Brain Research and Rehabilitation, South China Normal University, Guangzhou 510631, China
| | - Yukuan Tang
- Department of Minimally Invasive Interventional Radiology, Guangzhou Panyu Central Hospital, Guangzhou 511400, China;
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29
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Milošević N, Rütter M, David A. Endothelial Cell Adhesion Molecules- (un)Attainable Targets for Nanomedicines. FRONTIERS IN MEDICAL TECHNOLOGY 2022; 4:846065. [PMID: 35463298 PMCID: PMC9021548 DOI: 10.3389/fmedt.2022.846065] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/30/2021] [Accepted: 02/15/2022] [Indexed: 01/21/2023] Open
Abstract
Endothelial cell adhesion molecules have long been proposed as promising targets in many pathologies. Despite promising preclinical data, several efforts to develop small molecule inhibitors or monoclonal antibodies (mAbs) against cell adhesion molecules (CAMs) ended in clinical-stage failure. In parallel, many well-validated approaches for targeting CAMs with nanomedicine (NM) were reported over the years. A wide range of potential applications has been demonstrated in various preclinical studies, from drug delivery to the tumor vasculature, imaging of the inflamed endothelium, or blocking immune cells infiltration. However, no NM drug candidate emerged further into clinical development. In this review, we will summarize the most advanced examples of CAM-targeted NMs and juxtapose them with known traditional drugs against CAMs, in an attempt to identify important translational hurdles. Most importantly, we will summarize the proposed strategies to enhance endothelial CAM targeting by NMs, in an attempt to offer a catalog of tools for further development.
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Madonna R. Angiocrine endothelium: From physiology to atherosclerosis and cardiac repair. Vascul Pharmacol 2022; 144:106993. [DOI: 10.1016/j.vph.2022.106993] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/09/2022] [Revised: 03/25/2022] [Accepted: 03/30/2022] [Indexed: 02/08/2023]
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Li L, Liu S, Tan J, Wei L, Wu D, Gao S, Weng Y, Chen J. Recent advance in treatment of atherosclerosis: Key targets and plaque-positioned delivery strategies. J Tissue Eng 2022; 13:20417314221088509. [PMID: 35356091 PMCID: PMC8958685 DOI: 10.1177/20417314221088509] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/29/2022] Open
Abstract
Atherosclerosis, a chronic inflammatory disease of vascular wall, is a progressive pathophysiological process with lipids oxidation/depositing initiation and innate/adaptive immune responses. The coordination of multi systems covering oxidative stress, dysfunctional endothelium, diseased lipid uptake, cell apoptosis, thrombotic and pro-inflammatory responding as well as switched SMCs contributes to plaque growth. In this circumstance, inevitably, targeting these processes is considered to be effective for treating atherosclerosis. Arriving, retention and working of payload candidates mediated by targets in lesion direct ultimate therapeutic outcomes. Accumulating a series of scientific studies and clinical practice in the past decades, lesion homing delivery strategies including stent/balloon/nanoparticle-based transportation worked as the potent promotor to ensure a therapeutic effect. The objective of this review is to achieve a very brief summary about the effective therapeutic methods cooperating specifical targets and positioning-delivery strategies in atherosclerosis for better outcomes.
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Affiliation(s)
- Li Li
- Key Laboratory of Advanced Technology of Materials, Ministry of Education, Southwest Jiaotong University, Chengdu, PR China
| | - Sainan Liu
- Key Laboratory of Advanced Technology of Materials, Ministry of Education, Southwest Jiaotong University, Chengdu, PR China
| | - Jianying Tan
- Key Laboratory of Advanced Technology of Materials, Ministry of Education, Southwest Jiaotong University, Chengdu, PR China
| | - Lai Wei
- Key Laboratory of Advanced Technology of Materials, Ministry of Education, Southwest Jiaotong University, Chengdu, PR China
| | - Dimeng Wu
- Chengdu Daxan Innovative Medical Tech. Co., Ltd., Chengdu, PR China
| | - Shuai Gao
- Chengdu Daxan Innovative Medical Tech. Co., Ltd., Chengdu, PR China
| | - Yajun Weng
- Key Laboratory of Advanced Technology of Materials, Ministry of Education, Southwest Jiaotong University, Chengdu, PR China
| | - Junying Chen
- Key Laboratory of Advanced Technology of Materials, Ministry of Education, Southwest Jiaotong University, Chengdu, PR China
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Yang E, Liu Q, Huang G, Liu J, Wei W. Engineering nanobodies for next-generation molecular imaging. Drug Discov Today 2022; 27:1622-1638. [PMID: 35331925 DOI: 10.1016/j.drudis.2022.03.013] [Citation(s) in RCA: 29] [Impact Index Per Article: 9.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/30/2021] [Revised: 02/04/2022] [Accepted: 03/17/2022] [Indexed: 12/12/2022]
Abstract
In recent years, nanobodies have emerged as ideal imaging agents for molecular imaging. Molecular nanobody imaging combines the specificity of nanobodies with the sensitivity of state-of-the-art molecular imaging modalities, such as positron emission tomography (PET). Given that modifications of nanobodies alter their pharmacokinetics (PK), the engineering strategies that combine nanobodies with radionuclides determine the effectiveness, reliability, and safety of the molecular imaging probes. In this review, we introduce conjugation strategies that have been applied to nanobodies, including random conjugation, 99mTc tricarbonyl chemistry, sortase A-mediated site-specific conjugation, maleimide-cysteine chemistry, and click chemistries. We also summarize the latest advances in nanobody tracers, emphasizing their preclinical and clinical use. In addition, we elaborate on nanobody-based near-infrared fluorescence (NIRF) imaging and image-guided surgery.
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Affiliation(s)
- Erpeng Yang
- Department of Nuclear Medicine, Institute of Clinical Nuclear Medicine, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200217, China
| | - Qiufang Liu
- Department of Nuclear Medicine, Fudan University Shanghai Cancer Center, Fudan University, Shanghai 200032, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China
| | - Gang Huang
- Department of Nuclear Medicine, Institute of Clinical Nuclear Medicine, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200217, China
| | - Jianjun Liu
- Department of Nuclear Medicine, Institute of Clinical Nuclear Medicine, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200217, China.
| | - Weijun Wei
- Department of Nuclear Medicine, Institute of Clinical Nuclear Medicine, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200217, China.
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Zhang C, Huang W, Huang C, Zhou C, Tang Y, Wei W, Li Y, Tang Y, Luo Y, Zhou Q, Chen W. VHPKQHR Peptide Modified Ultrasmall Paramagnetic Iron Oxide Nanoparticles Targeting Rheumatoid Arthritis for T 1-Weighted Magnetic Resonance Imaging. Front Bioeng Biotechnol 2022; 10:821256. [PMID: 35295653 PMCID: PMC8918785 DOI: 10.3389/fbioe.2022.821256] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/24/2021] [Accepted: 01/14/2022] [Indexed: 11/18/2022] Open
Abstract
Magnetic resonance imaging (MRI) could be the ideal diagnostic modality for early rheumatoid arthritis (RA). Vascular cell adhesion molecule-1 (VCAM-1) is highly expressed in synovial locations in patients with RA, which could be a potential target protein for RA diagnosis. The peptide VHPKQHR (VHP) has a high affinity to VCAM-1. To make the contrast agent to target RA at an early stage, we used VHP and ultrasmall paramagnetic iron oxide (USPIO) to synthesize UVHP (U stands for USPIO) through a chemical reaction with 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride and N-hydroxysuccinimide. The size of UVHP was 6.7 nm; the potential was -27.7 mV, and the r 2/r 1 value was 1.73. Cytotoxicity assay exhibited that the cell survival rate was higher than 80% at even high concentrations of UVHP (Fe concentration 200 µg/mL), which showed the UVHP has low toxicity. Compared with no TNF-α stimulation, VCAM-1 expression was increased nearly 3-fold when mouse aortic endothelial cells (MAECs) were stimulated with 50 ng/mL TNF-α; cellular Fe uptake was increased very significantly with increasing UVHP concentration under TNF-α treatment; cellular Fe content was 17 times higher under UVHP with Fe concentration 200 µg/mL treating MAECs. These results indicate that UVHP can target overexpression of VCAM-1 at the cellular level. RA mice models were constructed with adjuvant-induced arthritis. In vivo MRI and biodistribution results show that the signal intensity of knee joints was increased significantly and Fe accumulation in RA model mice compared with normal wild-type mice after injecting UVHP 24 h. These results suggest that we have synthesized a simple, low-cost, and less toxic contrast agent UVHP, which targeted VCAM-1 for early-stage RA diagnosis and generates high contrast in T1-weighted MRI.
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Affiliation(s)
- Chunyu Zhang
- MOE Key Laboratory of Laser Life Science, Institute of Laser Life Science, College of Biophotonics, South China Normal University, Guangzhou, China
- Guangdong Provincial Key Laboratory of Laser Life Science, College of Biophotonics, South China Normal University, Guangzhou, China
- Guangzhou Key Laboratory of Spectral Analysis and Functional Probes, College of Biophotonics, South China Normal University, Guangzhou, China
| | - Wentao Huang
- MOE Key Laboratory of Laser Life Science, Institute of Laser Life Science, College of Biophotonics, South China Normal University, Guangzhou, China
- Guangdong Provincial Key Laboratory of Laser Life Science, College of Biophotonics, South China Normal University, Guangzhou, China
- Guangzhou Key Laboratory of Spectral Analysis and Functional Probes, College of Biophotonics, South China Normal University, Guangzhou, China
| | - Chen Huang
- Department of Minimally Invasive Interventional Radiology, Guangzhou Panyu Central Hospital, Guangzhou, China
| | - Chengqian Zhou
- Neuroscience Laboratory, Hugo Moser Research Institute at Kennedy Krieger, Baltimore, MD, United States
| | - Yukuan Tang
- Department of Minimally Invasive Interventional Radiology, Guangzhou Panyu Central Hospital, Guangzhou, China
| | - Wei Wei
- Institution of GuangDong Cord Blood Bank, Guangzhou, China
| | - Yongsheng Li
- Institution of GuangDong Cord Blood Bank, Guangzhou, China
| | - Yukuan Tang
- Department of Minimally Invasive Interventional Radiology, Guangzhou Panyu Central Hospital, Guangzhou, China
| | - Yu Luo
- Shanghai Engineering Technology Research Center for Pharmaceutical Intelligent Equipment, Shanghai Frontiers Science Research Center for Druggability of Cardiovascular Noncoding RNA, Institute for Frontier Medical Technology, College of Chemistry and Chemical Engineering, Shanghai University of Engineering Science, Shanghai, China
| | - Quan Zhou
- Department of Radiology, The Third Affiliated Hospital of Southern Medical University, Guangzhou, China
| | - Wenli Chen
- MOE Key Laboratory of Laser Life Science, Institute of Laser Life Science, College of Biophotonics, South China Normal University, Guangzhou, China
- Guangdong Provincial Key Laboratory of Laser Life Science, College of Biophotonics, South China Normal University, Guangzhou, China
- Guangzhou Key Laboratory of Spectral Analysis and Functional Probes, College of Biophotonics, South China Normal University, Guangzhou, China
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Tiwari A, Elgrably B, Saar G, Vandoorne K. Multi-Scale Imaging of Vascular Pathologies in Cardiovascular Disease. Front Med (Lausanne) 2022; 8:754369. [PMID: 35071257 PMCID: PMC8766766 DOI: 10.3389/fmed.2021.754369] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/06/2021] [Accepted: 12/13/2021] [Indexed: 12/28/2022] Open
Abstract
Cardiovascular disease entails systemic changes in the vasculature. The endothelial cells lining the blood vessels are crucial in the pathogenesis of cardiovascular disease. Healthy endothelial cells direct the blood flow to tissues as vasodilators and act as the systemic interface between the blood and tissues, supplying nutrients for vital organs, and regulating the smooth traffic of leukocytes into tissues. In cardiovascular diseases, when inflammation is sensed, endothelial cells adjust to the local or systemic inflammatory state. As the inflamed vasculature adjusts, changes in the endothelial cells lead to endothelial dysfunction, altered blood flow and permeability, expression of adhesion molecules, vessel wall inflammation, thrombosis, angiogenic processes, and extracellular matrix production at the endothelial cell level. Preclinical multi-scale imaging of these endothelial changes using optical, acoustic, nuclear, MRI, and multimodal techniques has progressed, due to technical advances and enhanced biological understanding on the interaction between immune and endothelial cells. While this review highlights biological processes that are related to changes in the cardiac vasculature during cardiovascular diseases, it also summarizes state-of-the-art vascular imaging techniques. The advantages and disadvantages of the different imaging techniques are highlighted, as well as their principles, methodologies, and preclinical and clinical applications with potential future directions. These multi-scale approaches of vascular imaging carry great potential to further expand our understanding of basic vascular biology, to enable early diagnosis of vascular changes and to provide sensitive diagnostic imaging techniques in the management of cardiovascular disease.
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Affiliation(s)
- Ashish Tiwari
- Faculty of Biomedical Engineering, Technion-Israel Institute of Technology, Haifa, Israel
| | - Betsalel Elgrably
- Faculty of Biomedical Engineering, Technion-Israel Institute of Technology, Haifa, Israel
| | - Galit Saar
- Biomedical Core Facility, Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel
| | - Katrien Vandoorne
- Faculty of Biomedical Engineering, Technion-Israel Institute of Technology, Haifa, Israel
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Wang X, Gao B, Feng Y. Recent advances in inhibiting atherosclerosis and restenosis: from pathogenic factors, therapeutic agents to nano-delivery strategies. J Mater Chem B 2022; 10:1685-1708. [DOI: 10.1039/d2tb00003b] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022]
Abstract
Due to dominant atherosclerosis etiology, cardiovascular diseases (CVDs) remain the leading cause of morbidity and mortality worldwide. In clinical trials, advanced atherosclerotic plaques can be removed by angioplasty and vascular...
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Naman S, Naryal S, Palliwal R, Paliwal SR, Baldi A. Combating atherosclerosis with nanodrug delivery approaches: from bench side to commercialization. DRUG DELIVERY SYSTEMS FOR METABOLIC DISORDERS 2022:97-136. [DOI: 10.1016/b978-0-323-99616-7.00021-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/06/2025]
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Zhou Z, Yeh CF, Mellas M, Oh MJ, Zhu J, Li J, Huang RT, Harrison DL, Shentu TP, Wu D, Lueckheide M, Carver L, Chung EJ, Leon L, Yang KC, Tirrell MV, Fang Y. Targeted polyelectrolyte complex micelles treat vascular complications in vivo. Proc Natl Acad Sci U S A 2021; 118:e2114842118. [PMID: 34880134 PMCID: PMC8685925 DOI: 10.1073/pnas.2114842118] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 11/01/2021] [Indexed: 01/09/2023] Open
Abstract
Vascular disease is a leading cause of morbidity and mortality in the United States and globally. Pathological vascular remodeling, such as atherosclerosis and stenosis, largely develop at arterial sites of curvature, branching, and bifurcation, where disturbed blood flow activates vascular endothelium. Current pharmacological treatments of vascular complications principally target systemic risk factors. Improvements are needed. We previously devised a targeted polyelectrolyte complex micelle to deliver therapeutic nucleotides to inflamed endothelium in vitro by displaying the peptide VHPKQHR targeting vascular cell adhesion molecule 1 (VCAM-1) on the periphery of the micelle. This paper explores whether this targeted nanomedicine strategy effectively treats vascular complications in vivo. Disturbed flow-induced microRNA-92a (miR-92a) has been linked to endothelial dysfunction. We have engineered a transgenic line (miR-92aEC-TG /Apoe-/- ) establishing that selective miR-92a overexpression in adult vascular endothelium causally promotes atherosclerosis in Apoe-/- mice. We tested the therapeutic effectiveness of the VCAM-1-targeting polyelectrolyte complex micelles to deliver miR-92a inhibitors and treat pathological vascular remodeling in vivo. VCAM-1-targeting micelles preferentially delivered miRNA inhibitors to inflamed endothelial cells in vitro and in vivo. The therapeutic effectiveness of anti-miR-92a therapy in treating atherosclerosis and stenosis in Apoe-/- mice is markedly enhanced by the VCAM-1-targeting polyelectrolyte complex micelles. These results demonstrate a proof of concept to devise polyelectrolyte complex micelle-based targeted nanomedicine approaches treating vascular complications in vivo.
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Affiliation(s)
- Zhengjie Zhou
- Pritzker School of Molecular Engineering, University of Chicago, Chicago, IL 60637
- Biological Sciences Division, Department of Medicine, University of Chicago, Chicago, IL 60637
| | - Chih-Fan Yeh
- Biological Sciences Division, Department of Medicine, University of Chicago, Chicago, IL 60637
- Division of Cardiology, Department of Internal Medicine and Cardiovascular Center, National Taiwan University Hospital, Taipei 100, Taiwan
| | - Michael Mellas
- Pritzker School of Molecular Engineering, University of Chicago, Chicago, IL 60637
| | - Myung-Jin Oh
- Biological Sciences Division, Department of Medicine, University of Chicago, Chicago, IL 60637
| | - Jiayu Zhu
- Biological Sciences Division, Department of Medicine, University of Chicago, Chicago, IL 60637
| | - Jin Li
- Biological Sciences Division, Department of Medicine, University of Chicago, Chicago, IL 60637
| | - Ru-Ting Huang
- Biological Sciences Division, Department of Medicine, University of Chicago, Chicago, IL 60637
| | - Devin L Harrison
- Biological Sciences Division, Department of Medicine, University of Chicago, Chicago, IL 60637
- Graduate Program in Biophysical Sciences, University of Chicago, Chicago, IL 60637
| | - Tzu-Pin Shentu
- Biological Sciences Division, Department of Medicine, University of Chicago, Chicago, IL 60637
| | - David Wu
- Biological Sciences Division, Department of Medicine, University of Chicago, Chicago, IL 60637
| | - Michael Lueckheide
- Pritzker School of Molecular Engineering, University of Chicago, Chicago, IL 60637
| | - Lauryn Carver
- Pritzker School of Molecular Engineering, University of Chicago, Chicago, IL 60637
- Biological Sciences Division, Department of Medicine, University of Chicago, Chicago, IL 60637
| | - Eun Ji Chung
- Pritzker School of Molecular Engineering, University of Chicago, Chicago, IL 60637
| | - Lorraine Leon
- Pritzker School of Molecular Engineering, University of Chicago, Chicago, IL 60637
| | - Kai-Chien Yang
- Division of Cardiology, Department of Internal Medicine and Cardiovascular Center, National Taiwan University Hospital, Taipei 100, Taiwan
| | - Matthew V Tirrell
- Pritzker School of Molecular Engineering, University of Chicago, Chicago, IL 60637;
- Graduate Program in Biophysical Sciences, University of Chicago, Chicago, IL 60637
- Materials Science Division, Argonne National Laboratory, Lemont, IL 60439
| | - Yun Fang
- Biological Sciences Division, Department of Medicine, University of Chicago, Chicago, IL 60637;
- Graduate Program in Biophysical Sciences, University of Chicago, Chicago, IL 60637
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Ren F, Jiang Z, Han M, Zhang H, Yun B, Zhu H, Li Z. NIR‐II Fluorescence imaging for cerebrovascular diseases. VIEW 2021. [DOI: 10.1002/viw.20200128] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022] Open
Affiliation(s)
- Feng Ren
- Center for Molecular Imaging and Nuclear Medicine State Key Laboratory of Radiation Medicine and Protection School for Radiological and Interdisciplinary Sciences (RAD‐X) Soochow University, Collaborative Innovation Center of Radiation Medicine of Jiangsu Higher Education Institutions Suzhou 215123 P. R. China
| | - Zhilin Jiang
- Center for Molecular Imaging and Nuclear Medicine State Key Laboratory of Radiation Medicine and Protection School for Radiological and Interdisciplinary Sciences (RAD‐X) Soochow University, Collaborative Innovation Center of Radiation Medicine of Jiangsu Higher Education Institutions Suzhou 215123 P. R. China
| | - Mengxiao Han
- Center for Molecular Imaging and Nuclear Medicine State Key Laboratory of Radiation Medicine and Protection School for Radiological and Interdisciplinary Sciences (RAD‐X) Soochow University, Collaborative Innovation Center of Radiation Medicine of Jiangsu Higher Education Institutions Suzhou 215123 P. R. China
| | - Hao Zhang
- Center for Molecular Imaging and Nuclear Medicine State Key Laboratory of Radiation Medicine and Protection School for Radiological and Interdisciplinary Sciences (RAD‐X) Soochow University, Collaborative Innovation Center of Radiation Medicine of Jiangsu Higher Education Institutions Suzhou 215123 P. R. China
| | - Baofeng Yun
- Center for Molecular Imaging and Nuclear Medicine State Key Laboratory of Radiation Medicine and Protection School for Radiological and Interdisciplinary Sciences (RAD‐X) Soochow University, Collaborative Innovation Center of Radiation Medicine of Jiangsu Higher Education Institutions Suzhou 215123 P. R. China
| | - Hongqin Zhu
- Center for Molecular Imaging and Nuclear Medicine State Key Laboratory of Radiation Medicine and Protection School for Radiological and Interdisciplinary Sciences (RAD‐X) Soochow University, Collaborative Innovation Center of Radiation Medicine of Jiangsu Higher Education Institutions Suzhou 215123 P. R. China
| | - Zhen Li
- Center for Molecular Imaging and Nuclear Medicine State Key Laboratory of Radiation Medicine and Protection School for Radiological and Interdisciplinary Sciences (RAD‐X) Soochow University, Collaborative Innovation Center of Radiation Medicine of Jiangsu Higher Education Institutions Suzhou 215123 P. R. China
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Pan Q, Xu J, Wen CJ, Xiong YY, Gong ZT, Yang YJ. Nanoparticles: Promising Tools for the Treatment and Prevention of Myocardial Infarction. Int J Nanomedicine 2021; 16:6719-6747. [PMID: 34621124 PMCID: PMC8491866 DOI: 10.2147/ijn.s328723] [Citation(s) in RCA: 20] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/13/2021] [Accepted: 09/17/2021] [Indexed: 12/12/2022] Open
Abstract
Despite several recent advances, current therapy and prevention strategies for myocardial infarction are far from satisfactory, owing to limitations in their applicability and treatment effects. Nanoparticles (NPs) enable the targeted and stable delivery of therapeutic compounds, enhance tissue engineering processes, and regulate the behaviour of transplants such as stem cells. Thus, NPs may be more effective than other mechanisms, and may minimize potential adverse effects. This review provides evidence for the view that function-oriented systems are more practical than traditional material-based systems; it also summarizes the latest advances in NP-based strategies for the treatment and prevention of myocardial infarction.
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Affiliation(s)
- Qi Pan
- State Key Laboratory of Cardiovascular Disease, Department of Cardiology, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People's Republic of China
| | - Jing Xu
- State Key Laboratory of Cardiovascular Disease, Department of Cardiology, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People's Republic of China
| | - Cen-Jin Wen
- Department of Cardiology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People's Republic of China
| | - Yu-Yan Xiong
- State Key Laboratory of Cardiovascular Disease, Department of Cardiology, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People's Republic of China
| | - Zhao-Ting Gong
- State Key Laboratory of Cardiovascular Disease, Department of Cardiology, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People's Republic of China
| | - Yue-Jin Yang
- State Key Laboratory of Cardiovascular Disease, Department of Cardiology, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People's Republic of China
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Friedrich RP, Cicha I, Alexiou C. Iron Oxide Nanoparticles in Regenerative Medicine and Tissue Engineering. NANOMATERIALS 2021; 11:nano11092337. [PMID: 34578651 PMCID: PMC8466586 DOI: 10.3390/nano11092337] [Citation(s) in RCA: 54] [Impact Index Per Article: 13.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 08/23/2021] [Revised: 09/03/2021] [Accepted: 09/06/2021] [Indexed: 12/13/2022]
Abstract
In recent years, many promising nanotechnological approaches to biomedical research have been developed in order to increase implementation of regenerative medicine and tissue engineering in clinical practice. In the meantime, the use of nanomaterials for the regeneration of diseased or injured tissues is considered advantageous in most areas of medicine. In particular, for the treatment of cardiovascular, osteochondral and neurological defects, but also for the recovery of functions of other organs such as kidney, liver, pancreas, bladder, urethra and for wound healing, nanomaterials are increasingly being developed that serve as scaffolds, mimic the extracellular matrix and promote adhesion or differentiation of cells. This review focuses on the latest developments in regenerative medicine, in which iron oxide nanoparticles (IONPs) play a crucial role for tissue engineering and cell therapy. IONPs are not only enabling the use of non-invasive observation methods to monitor the therapy, but can also accelerate and enhance regeneration, either thanks to their inherent magnetic properties or by functionalization with bioactive or therapeutic compounds, such as drugs, enzymes and growth factors. In addition, the presence of magnetic fields can direct IONP-labeled cells specifically to the site of action or induce cell differentiation into a specific cell type through mechanotransduction.
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Zia A, Wu Y, Nguyen T, Wang X, Peter K, Ta HT. The choice of targets and ligands for site-specific delivery of nanomedicine to atherosclerosis. Cardiovasc Res 2021; 116:2055-2068. [PMID: 32077918 DOI: 10.1093/cvr/cvaa047] [Citation(s) in RCA: 37] [Impact Index Per Article: 9.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/30/2019] [Revised: 12/23/2019] [Accepted: 02/17/2020] [Indexed: 12/22/2022] Open
Abstract
As nanotechnologies advance into clinical medicine, novel methods for applying nanomedicine to cardiovascular diseases are emerging. Extensive research has been undertaken to unlock the complex pathogenesis of atherosclerosis. However, this complexity presents challenges to develop effective imaging and therapeutic modalities for early diagnosis and acute intervention. The choice of ligand-receptor system vastly influences the effectiveness of nanomedicine. This review collates current ligand-receptor systems used in targeting functionalized nanoparticles for diagnosis and treatment of atherosclerosis. Our focus is on the binding affinity and selectivity of ligand-receptor systems, as well as the relative abundance of targets throughout the development and progression of atherosclerosis. Antibody-based targeting systems are currently the most commonly researched due to their high binding affinities when compared with other ligands, such as antibody fragments, peptides, and other small molecules. However, antibodies tend to be immunogenic due to their size. Engineering antibody fragments can address this issue but will compromise their binding affinity. Peptides are promising ligands due to their synthetic flexibility and low production costs. Alongside the aforementioned binding affinity of ligands, the choice of target and its abundance throughout distinct stages of atherosclerosis and thrombosis is relevant to the intended purpose of the nanomedicine. Further studies to investigate the components of atherosclerotic plaques are required as their cellular and molecular profile shifts over time.
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Affiliation(s)
- Adil Zia
- Australian Institute for Bioengineering and Nanotechnology, The University of Queensland, Brisbane, QLD 4072, Australia
| | - Yuao Wu
- Australian Institute for Bioengineering and Nanotechnology, The University of Queensland, Brisbane, QLD 4072, Australia.,School of Pharmacy, Pharmacy Australia Centre of Excellence, The University of Queensland, Woolloongabba, QLD 4102, Australia
| | - Tuan Nguyen
- School of Chemical Engineering, The University of Queensland, Brisbane, QLD 4072, Australia
| | - Xiaowei Wang
- Baker Heart and Diabetes Institute, Melbourne, VIC 3000, Australia
| | - Karlheinz Peter
- Baker Heart and Diabetes Institute, Melbourne, VIC 3000, Australia
| | - Hang T Ta
- Australian Institute for Bioengineering and Nanotechnology, The University of Queensland, Brisbane, QLD 4072, Australia.,School of Pharmacy, Pharmacy Australia Centre of Excellence, The University of Queensland, Woolloongabba, QLD 4102, Australia
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Pharmacokinetics of Single Domain Antibodies and Conjugated Nanoparticles Using a Hybrid near Infrared Method. Int J Mol Sci 2021; 22:ijms22168695. [PMID: 34445399 PMCID: PMC8395466 DOI: 10.3390/ijms22168695] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/29/2021] [Revised: 08/05/2021] [Accepted: 08/09/2021] [Indexed: 11/17/2022] Open
Abstract
Iron oxide nanoparticles and single domain antibodies from camelids (VHHs) have been increasingly recognized for their potential uses for medical diagnosis and treatment. However, there have been relatively few detailed characterizations of their pharmacokinetics (PK). The aim of this study was to develop imaging methods and pharmacokinetic models to aid the future development of a novel family of brain MRI molecular contrast agents. An efficient near-infrared (NIR) imaging method was established to monitor VHH and VHH conjugated nanoparticle kinetics in mice using a hybrid approach: kinetics in blood were assessed by direct sampling, and kinetics in kidney, liver, and brain were assessed by serial in vivo NIR imaging. These studies were performed under "basal" circumstances in which the VHH constructs and VHH-conjugated nanoparticles do not substantially interact with targets nor cross the blood brain barrier. Using this approach, we constructed a five-compartment PK model that fits the data well for single VHHs, engineered VHH trimers, and iron oxide nanoparticles conjugated to VHH trimers. The establishment of the feasibility of these methods lays a foundation for future PK studies of candidate brain MRI molecular contrast agents.
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MacRitchie N, Di Francesco V, Ferreira MFMM, Guzik TJ, Decuzzi P, Maffia P. Nanoparticle theranostics in cardiovascular inflammation. Semin Immunol 2021; 56:101536. [PMID: 34862118 PMCID: PMC8811479 DOI: 10.1016/j.smim.2021.101536] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/02/2021] [Revised: 11/17/2021] [Accepted: 11/18/2021] [Indexed: 12/30/2022]
Abstract
Theranostics, literally derived from the combination of the words diagnostics and therapy, is an emerging field of clinical and preclinical research, where contrast agents, drugs and diagnostic techniques are combined to simultaneously diagnose and treat pathologies. Nanoparticles are extensively employed in theranostics due to their potential to target specific organs and their multifunctional capacity. In this review, we will discuss the current state of theranostic nanomedicine, providing key examples of its application in the imaging and treatment of cardiovascular inflammation.
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Affiliation(s)
- Neil MacRitchie
- Centre for Immunobiology, Institute of Infection, Immunity and Inflammation, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, United Kingdom.
| | - Valentina Di Francesco
- Laboratory of Nanotechnology for Precision Medicine, Fondazione Istituto Italiano di Tecnologia, Genoa, Italy
| | | | - Tomasz J Guzik
- Institute of Cardiovascular and Medical Sciences, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, United Kingdom; Department of Internal Medicine, Jagiellonian University, Collegium Medicum, Kraków, Poland
| | - Paolo Decuzzi
- Laboratory of Nanotechnology for Precision Medicine, Fondazione Istituto Italiano di Tecnologia, Genoa, Italy
| | - Pasquale Maffia
- Centre for Immunobiology, Institute of Infection, Immunity and Inflammation, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, United Kingdom; Institute of Cardiovascular and Medical Sciences, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, United Kingdom; Department of Pharmacy, School of Medicine and Surgery, University of Naples Federico II, Naples, Italy.
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Dosta P, Tamargo I, Ramos V, Kumar S, Kang DW, Borrós S, Jo H. Delivery of Anti-microRNA-712 to Inflamed Endothelial Cells Using Poly(β-amino ester) Nanoparticles Conjugated with VCAM-1 Targeting Peptide. Adv Healthc Mater 2021; 10:e2001894. [PMID: 33448151 PMCID: PMC8277885 DOI: 10.1002/adhm.202001894] [Citation(s) in RCA: 42] [Impact Index Per Article: 10.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/27/2020] [Revised: 12/04/2020] [Indexed: 12/15/2022]
Abstract
Endothelial cells (ECs) are an important target for therapy in a wide range of diseases, most notably atherosclerosis. Developing efficient nanoparticle (NP) systems that deliver RNA interference (RNAi) drugs specifically to dysfunctional ECs in vivo to modulate their gene expression remains a challenge. To date, several lipid-based NPs are developed and shown to deliver RNAi to ECs, but few of them are optimized to specifically target dysfunctional endothelium. Here, a novel, targeted poly(β-amino ester) (pBAE) NP is demonstrated. This pBAE NP is conjugated with VHPK peptides that target vascular cell adhesion molecule 1 protein, overexpressed on inflamed EC membranes. To test this approach, the novel NPs are used to deliver anti-microRNA-712 (anti-miR-712) specifically to inflamed ECs both in vitro and in vivo, reducing the high expression of pro-atherogenic miR-712. A single administration of anti-miR-712 using the VHPK-conjugated-pBAE NPs in mice significantly reduce miR-712 expression, while preventing the loss of its target gene, tissue inhibitor of metalloproteinase 3 (TIMP3) in inflamed endothelium. miR-712 and TIMP3 expression are unchanged in non-inflamed endothelium. This novel, targeted-delivery platform may be used to deliver RNA therapeutics specifically to dysfunctional endothelium for the treatment of vascular disease.
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Affiliation(s)
- Pere Dosta
- Wallace H. Coulter Department of Biomedical Engineering and Division of Cardiology, Georgia Institute of Technology and Emory University, Atlanta, Georgia, 30332, USA
- Grup d'Enginyera de Materials (GEMAT) Institut Químic de Sarrià, Universitat Ramon Llull, Barcelona, 08017, Spain
| | - Ian Tamargo
- Wallace H. Coulter Department of Biomedical Engineering and Division of Cardiology, Georgia Institute of Technology and Emory University, Atlanta, Georgia, 30332, USA
| | - Victor Ramos
- Grup d'Enginyera de Materials (GEMAT) Institut Químic de Sarrià, Universitat Ramon Llull, Barcelona, 08017, Spain
| | - Sandeep Kumar
- Wallace H. Coulter Department of Biomedical Engineering and Division of Cardiology, Georgia Institute of Technology and Emory University, Atlanta, Georgia, 30332, USA
| | - Dong Won Kang
- Wallace H. Coulter Department of Biomedical Engineering and Division of Cardiology, Georgia Institute of Technology and Emory University, Atlanta, Georgia, 30332, USA
| | - Salvador Borrós
- Grup d'Enginyera de Materials (GEMAT) Institut Químic de Sarrià, Universitat Ramon Llull, Barcelona, 08017, Spain
| | - Hanjoong Jo
- Wallace H. Coulter Department of Biomedical Engineering and Division of Cardiology, Georgia Institute of Technology and Emory University, Atlanta, Georgia, 30332, USA
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45
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Zhong Y, Qin X, Wang Y, Qu K, Luo L, Zhang K, Liu B, Obaid EAMS, Wu W, Wang G. "Plug and Play" Functionalized Erythrocyte Nanoplatform for Target Atherosclerosis Management. ACS APPLIED MATERIALS & INTERFACES 2021; 13:33862-33873. [PMID: 34256560 DOI: 10.1021/acsami.1c07821] [Citation(s) in RCA: 25] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/13/2023]
Abstract
For atherosclerosis (AS) management, a therapeutic drug intervention is the most widely used strategy. However, there are some problems such as low location specificity, high intake, and side effects. Nanomedicine can prolong the half-life of drug solubilization, reduce toxic and side effects, and improve the distribution of drug objects. Herein, to overcome the challenges, an erythrocyte-based "plug and play" nanoplatform was developed by incorporating the vascular cell adhesion molecule-1 (VCAM-1) targeting and the acid stimulus responsibility. After the function moieties conjugated with DSPE-PEG, the targeting peptide and the acid-sensitive prodrug were conveniently integrated into red blood cells' surface for enhancing target AS drug delivery and controlling local drug release. As a proof of principle, a plug and play nanoplatform with targeted drug delivery and acid-control drug release is demonstrated, achieving a marked therapeutic effect for AS.
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Affiliation(s)
- Yuan Zhong
- Key Laboratory for Biorheological Science and Technology of Ministry of Education, State and Local Joint Engineering Laboratory for Vascular Implants, Bioengineering College of Chongqing University, Chongqing 400030, China
| | - Xian Qin
- Key Laboratory for Biorheological Science and Technology of Ministry of Education, State and Local Joint Engineering Laboratory for Vascular Implants, Bioengineering College of Chongqing University, Chongqing 400030, China
| | - Yi Wang
- Key Laboratory for Biorheological Science and Technology of Ministry of Education, State and Local Joint Engineering Laboratory for Vascular Implants, Bioengineering College of Chongqing University, Chongqing 400030, China
| | - Kai Qu
- Key Laboratory for Biorheological Science and Technology of Ministry of Education, State and Local Joint Engineering Laboratory for Vascular Implants, Bioengineering College of Chongqing University, Chongqing 400030, China
| | - Li Luo
- Key Laboratory for Biorheological Science and Technology of Ministry of Education, State and Local Joint Engineering Laboratory for Vascular Implants, Bioengineering College of Chongqing University, Chongqing 400030, China
| | - Kun Zhang
- Key Laboratory for Biorheological Science and Technology of Ministry of Education, State and Local Joint Engineering Laboratory for Vascular Implants, Bioengineering College of Chongqing University, Chongqing 400030, China
| | - Boyan Liu
- Key Laboratory for Biorheological Science and Technology of Ministry of Education, State and Local Joint Engineering Laboratory for Vascular Implants, Bioengineering College of Chongqing University, Chongqing 400030, China
| | - Essam Abdo Mohammed Saad Obaid
- Key Laboratory for Biorheological Science and Technology of Ministry of Education, State and Local Joint Engineering Laboratory for Vascular Implants, Bioengineering College of Chongqing University, Chongqing 400030, China
| | - Wei Wu
- Key Laboratory for Biorheological Science and Technology of Ministry of Education, State and Local Joint Engineering Laboratory for Vascular Implants, Bioengineering College of Chongqing University, Chongqing 400030, China
| | - Guixue Wang
- Key Laboratory for Biorheological Science and Technology of Ministry of Education, State and Local Joint Engineering Laboratory for Vascular Implants, Bioengineering College of Chongqing University, Chongqing 400030, China
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Nakamura M, Kosuge H, Oyane A, Kuroiwa K, Shimizu Y, Aonuma K. In vivostudy of iron oxide-calcium phosphate composite nanoparticles for delivery to atherosclerosis. NANOTECHNOLOGY 2021; 32:345101. [PMID: 34057430 DOI: 10.1088/1361-6528/ac007d] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/22/2021] [Accepted: 05/12/2021] [Indexed: 06/12/2023]
Abstract
Atherosclerosis is a macrophage-related inflammatory disease that remains a leading cause of death worldwide. Magnetic iron oxide (IO) nanocrystals are clinically used as magnetic resonance imaging contrast agents and their application as a detection agent for macrophages in arterial lesions has been studied extensively. We recently fabricated heparin-modified calcium phosphate (CaP) nanoparticles loaded with a large number of IO nanocrystals via coprecipitation from a supersaturated CaP solution supplemented with heparin and ferucarbotran (IO nanocrystals coated with carboxydextran). In this study, we further increased the content of IO nanocrystals in the heparin-modified IO-CaP composite nanoparticles by increasing the ferucarbotran concentration in the supersaturated CaP solution. The increase in nanoparticle IO content caused a decrease in particle diameter without impairing its dispersibility; the nanoparticles remained dispersed in water for up to 2 h due to electrostatic repulsion between particles due to the surface modification with heparin. The nanoparticles were more effectively taken up by murine RAW264.7 macrophages compared to free ferucarbotran without showing significant cytotoxicity. A preliminaryin vivostudy showed that the nanoparticles injected intravenously into mice delivered more IO nanocrystals to macrophage-rich carotid arterial lesions than free ferucarbotran. Our nanoparticles have potential as a delivery agent of IO nanocrystals to macrophages in arterial lesions.
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Affiliation(s)
- Maki Nakamura
- Nanomaterials Research Institute, National Institute of Advanced Industrial Science and Technology (AIST), Central 5, 1-1-1 Higashi, Tsukuba, Ibaraki 305-8565, Japan
| | - Hisanori Kosuge
- Department of Cardiology, Tokyo Medical University, 6-7-1 Nishishinjuku, Shinjuku-ku, Tokyo 160-0023, Japan
- Department of Cardiology, Faculty of Medicine, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8575, Japan
| | - Ayako Oyane
- Nanomaterials Research Institute, National Institute of Advanced Industrial Science and Technology (AIST), Central 5, 1-1-1 Higashi, Tsukuba, Ibaraki 305-8565, Japan
| | - Kiyoko Kuroiwa
- Nanomaterials Research Institute, National Institute of Advanced Industrial Science and Technology (AIST), Central 5, 1-1-1 Higashi, Tsukuba, Ibaraki 305-8565, Japan
| | - Yoshiki Shimizu
- Nanomaterials Research Institute, National Institute of Advanced Industrial Science and Technology (AIST), Central 5, 1-1-1 Higashi, Tsukuba, Ibaraki 305-8565, Japan
| | - Kazutaka Aonuma
- Department of Cardiology, Faculty of Medicine, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8575, Japan
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Hwang HS, Kim H, Han G, Lee JW, Kim K, Kwon IC, Yang Y, Kim SH. Extracellular Vesicles as Potential Therapeutics for Inflammatory Diseases. Int J Mol Sci 2021; 22:5487. [PMID: 34067503 PMCID: PMC8196952 DOI: 10.3390/ijms22115487] [Citation(s) in RCA: 23] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/04/2021] [Accepted: 05/17/2021] [Indexed: 12/11/2022] Open
Abstract
Extracellular vesicles (EV) deliver cargoes such as nucleic acids, proteins, and lipids between cells and serve as an intercellular communicator. As it is revealed that most of the functions associated to EVs are closely related to the immune response, the important role of EVs in inflammatory diseases is emerging. EVs can be functionalized through EV surface engineering and endow targeting moiety that allows for the target specificity for therapeutic applications in inflammatory diseases. Moreover, engineered EVs are considered as promising nanoparticles to develop personalized therapeutic carriers. In this review, we highlight the role of EVs in various inflammatory diseases, the application of EV as anti-inflammatory therapeutics, and the current state of the art in EV engineering techniques.
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Affiliation(s)
- Hee Sook Hwang
- Center for Theragnosis, Biomedical Research Institute, Korea Institute of Science and Technology (KIST), Seoul 02792, Korea; (H.S.H.); (H.K.); (G.H.); (J.W.L.); (K.K.); (I.C.K.)
- Department of Pharmaceutical Engineering, Dankook University, Cheonan 31116, Korea
| | - Hyosuk Kim
- Center for Theragnosis, Biomedical Research Institute, Korea Institute of Science and Technology (KIST), Seoul 02792, Korea; (H.S.H.); (H.K.); (G.H.); (J.W.L.); (K.K.); (I.C.K.)
| | - Geonhee Han
- Center for Theragnosis, Biomedical Research Institute, Korea Institute of Science and Technology (KIST), Seoul 02792, Korea; (H.S.H.); (H.K.); (G.H.); (J.W.L.); (K.K.); (I.C.K.)
- KU-KIST Graduate School of Converging Science and Technology, Korea University, Seoul 02841, Korea
| | - Jong Won Lee
- Center for Theragnosis, Biomedical Research Institute, Korea Institute of Science and Technology (KIST), Seoul 02792, Korea; (H.S.H.); (H.K.); (G.H.); (J.W.L.); (K.K.); (I.C.K.)
- KU-KIST Graduate School of Converging Science and Technology, Korea University, Seoul 02841, Korea
| | - Kwangmeyung Kim
- Center for Theragnosis, Biomedical Research Institute, Korea Institute of Science and Technology (KIST), Seoul 02792, Korea; (H.S.H.); (H.K.); (G.H.); (J.W.L.); (K.K.); (I.C.K.)
- KU-KIST Graduate School of Converging Science and Technology, Korea University, Seoul 02841, Korea
| | - Ick Chan Kwon
- Center for Theragnosis, Biomedical Research Institute, Korea Institute of Science and Technology (KIST), Seoul 02792, Korea; (H.S.H.); (H.K.); (G.H.); (J.W.L.); (K.K.); (I.C.K.)
- KU-KIST Graduate School of Converging Science and Technology, Korea University, Seoul 02841, Korea
- Department of Cancer Biology, Dana-Farber Cancer Institute, 450 Brookline Avenue, Boston, MA 02215, USA
| | - Yoosoo Yang
- Center for Theragnosis, Biomedical Research Institute, Korea Institute of Science and Technology (KIST), Seoul 02792, Korea; (H.S.H.); (H.K.); (G.H.); (J.W.L.); (K.K.); (I.C.K.)
| | - Sun Hwa Kim
- Center for Theragnosis, Biomedical Research Institute, Korea Institute of Science and Technology (KIST), Seoul 02792, Korea; (H.S.H.); (H.K.); (G.H.); (J.W.L.); (K.K.); (I.C.K.)
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48
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Zarubova J, Zhang X, Hoffman T, Hasani-Sadrabadi MM, Li S. Biomaterial-based immunoengineering to fight COVID-19 and infectious diseases. MATTER 2021; 4:1528-1554. [PMID: 33723531 PMCID: PMC7942141 DOI: 10.1016/j.matt.2021.02.025] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/04/2023]
Abstract
Infection by SARS-CoV-2 virus often induces the dysregulation of immune responses, tissue damage, and blood clotting. Engineered biomaterials from the nano- to the macroscale can provide targeted drug delivery, controlled drug release, local immunomodulation, enhanced immunity, and other desirable functions to coordinate appropriate immune responses and to repair tissues. Based on the understanding of COVID-19 disease progression and immune responses to SARS-CoV-2, we discuss possible immunotherapeutic strategies and highlight biomaterial approaches from the perspectives of preventive immunization, therapeutic immunomodulation, and tissue healing and regeneration. Successful development of biomaterial platforms for immunization and immunomodulation will not only benefit COVID-19 patients, but also have broad applications for a variety of infectious diseases.
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Affiliation(s)
- Jana Zarubova
- Department of Bioengineering, Henry Samueli School of Engineering and Applied Science, University of California, Los Angeles, CA 90095, USA
| | - Xuexiang Zhang
- Department of Bioengineering, Henry Samueli School of Engineering and Applied Science, University of California, Los Angeles, CA 90095, USA
| | - Tyler Hoffman
- Department of Bioengineering, Henry Samueli School of Engineering and Applied Science, University of California, Los Angeles, CA 90095, USA
| | - Mohammad Mahdi Hasani-Sadrabadi
- Department of Bioengineering, Henry Samueli School of Engineering and Applied Science, University of California, Los Angeles, CA 90095, USA
| | - Song Li
- Department of Bioengineering, Henry Samueli School of Engineering and Applied Science, University of California, Los Angeles, CA 90095, USA
- Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA
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49
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Monteserín M, Larumbe S, Martínez AV, Burgui S, Francisco Martín L. Recent Advances in the Development of Magnetic Nanoparticles for Biomedical Applications. JOURNAL OF NANOSCIENCE AND NANOTECHNOLOGY 2021; 21:2705-2741. [PMID: 33653440 DOI: 10.1166/jnn.2021.19062] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/12/2023]
Abstract
The unique properties of magnetic nanoparticles have led them to be considered materials with significant potential in the biomedical field. Nanometric size, high surface-area ratio, ability to function at molecular level, exceptional magnetic and physicochemical properties, and more importantly, the relatively easy tailoring of all these properties to the specific requirements of the different biomedical applications, are some of the key factors of their success. In this paper, we will provide an overview of the state of the art of different aspects of magnetic nanoparticles, specially focusing on their use in biomedicine. We will explore their magnetic properties, synthetic methods and surface modifications, as well as their most significative physicochemical properties and their impact on the in vivo behaviour of these particles. Furthermore, we will provide a background on different applications of magnetic nanoparticles in biomedicine, such as magnetic drug targeting, magnetic hyperthermia, imaging contrast agents or theranostics. Besides, current limitations and challenges of these materials, as well as their future prospects in the biomedical field will be discussed.
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Affiliation(s)
- Maria Monteserín
- Centre of Advanced Surface Engineering and Advanced Materials, Asociación de la Industria Navarra, Ctra. Pamplona, s/n, Edificio AIN, C.P. 31191, Cordovilla, Navarra (Spain)
| | - Silvia Larumbe
- Centre of Advanced Surface Engineering and Advanced Materials, Asociación de la Industria Navarra, Ctra. Pamplona, s/n, Edificio AIN, C.P. 31191, Cordovilla, Navarra (Spain)
| | - Alejandro V Martínez
- Centre of Advanced Surface Engineering and Advanced Materials, Asociación de la Industria Navarra, Ctra. Pamplona, s/n, Edificio AIN, C.P. 31191, Cordovilla, Navarra (Spain)
| | - Saioa Burgui
- Centre of Advanced Surface Engineering and Advanced Materials, Asociación de la Industria Navarra, Ctra. Pamplona, s/n, Edificio AIN, C.P. 31191, Cordovilla, Navarra (Spain)
| | - L Francisco Martín
- Centre of Advanced Surface Engineering and Advanced Materials, Asociación de la Industria Navarra, Ctra. Pamplona, s/n, Edificio AIN, C.P. 31191, Cordovilla, Navarra (Spain)
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50
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Day K, Schneible JD, Young AT, Pozdin VA, Van Den Driessche G, Gaffney LA, Prodromou R, Freytes DO, Fourches D, Daniele M, Menegatti S. Photoinduced reconfiguration to control the protein-binding affinity of azobenzene-cyclized peptides. J Mater Chem B 2021; 8:7413-7427. [PMID: 32661544 DOI: 10.1039/d0tb01189d] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
The impact of next-generation biorecognition elements (ligands) will be determined by the ability to remotely control their binding activity for a target biomolecule in complex environments. Compared to conventional mechanisms for regulating binding affinity (pH, ionic strength, or chaotropic agents), light provides higher accuracy and rapidity, and is particularly suited for labile targets. In this study, we demonstrate a general method to develop azobenzene-cyclized peptide ligands with light-controlled affinity for target proteins. Light triggers a cis/trans isomerization of the azobenzene, which results in a major structural rearrangement of the cyclic peptide from a non-binding to a binding configuration. Critical to this goal are the ability to achieve efficient photo-isomerization under low light dosage and the temporal stability of both cis and trans isomers. We demonstrated our method by designing photo-switchable peptides targeting vascular cell adhesion marker 1 (VCAM1), a cell marker implicated in stem cell function. Starting from a known VCAM1-binding linear peptide, an ensemble of azobenzene-cyclized variants with selective light-controlled binding were identified by combining in silico design with experimental characterization via spectroscopy and surface plasmon resonance. Variant cycloAZOB[G-VHAKQHRN-K] featured rapid, light-controlled binding of VCAM1 (KD,trans/KD,cis ∼ 130). Biotin-cycloAZOB[G-VHAKQHRN-K] was utilized to label brain microvascular endothelial cells (BMECs), showing co-localization with anti-VCAM1 antibodies in cis configuration and negligible binding in trans configuration.
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Affiliation(s)
- Kevin Day
- Department of Chemical and Biomolecular Engineering, North Carolina State University, 911 Partners Way, Raleigh, North Carolina, USA.
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