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Gao Y, Zhang L, Wang Z, Bai H, Wu C, Shuai Q, Yan Y. Enhanced Pulmonary and Splenic mRNA Delivery Using DOTAP-Incorporated Poly(β-Amino Ester)-Lipid Nanoparticles. Biomacromolecules 2025; 26:623-634. [PMID: 39746921 DOI: 10.1021/acs.biomac.4c01445] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
Abstract
mRNA-based therapies hold tremendous promise for treating various diseases, yet their clinical success is hindered by delivery challenges. This study developed a library of 140 lipocationic Poly(β-amino ester)s (PBAEs) and formulated lipid-polymer hybrid nanoparticles (LPHs) with four helper lipids, including 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP), to enhance mRNA delivery. Initial in vitro screening of four representative PBAEs identified the D/P4-1 formulation (DOTAP/PBAE molar ratio of 4:1) as the most effective. Further screening of the library using this formulation identified eight top-performing LPHs. In vivo experiments confirmed high luciferase expression in the spleen and lungs of mice following intravenous administration of Luc mRNA-loaded LPHs. Detailed analysis revealed that DOTAP incorporation influenced LPH properties, including apparent pKa, surface charge, and internal hydrophobicity, enabling enhanced mRNA release and cellular uptake. This study demonstrates potent approaches to modulate PBAE-lipid nanoparticle properties by altering PBAE structures and nanoparticle composition, offering insights for designing effective hybrid carriers for mRNA therapeutics.
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Affiliation(s)
- Yuduo Gao
- College of Biotechnology and Bioengineering, Zhejiang University of Technology, Hangzhou, Zhejiang 310014, China
| | - Luwei Zhang
- College of Biotechnology and Bioengineering, Zhejiang University of Technology, Hangzhou, Zhejiang 310014, China
| | - Ziyue Wang
- College of Biotechnology and Bioengineering, Zhejiang University of Technology, Hangzhou, Zhejiang 310014, China
| | - Hao Bai
- College of Biotechnology and Bioengineering, Zhejiang University of Technology, Hangzhou, Zhejiang 310014, China
| | - Chengfan Wu
- College of Biotechnology and Bioengineering, Zhejiang University of Technology, Hangzhou, Zhejiang 310014, China
| | - Qi Shuai
- Collaborative Innovation Center of Yangtze River Delta Region Green Pharmaceuticals, Zhejiang University of Technology, Hangzhou, Zhejiang 310014, China
| | - Yunfeng Yan
- College of Biotechnology and Bioengineering, Zhejiang University of Technology, Hangzhou, Zhejiang 310014, China
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Cai C, Song Z, Xu X, Yang X, Wei S, Chen F, Dong X, Zhang X, Zhu Y. The neurotoxicity of acrylamide in ultra-processed foods: interventions of polysaccharides through the microbiota-gut-brain axis. Food Funct 2025; 16:10-23. [PMID: 39611232 DOI: 10.1039/d4fo03002h] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/30/2024]
Abstract
Ultra-processed foods (UPFs) have become popular in recent years, however, the detrimental effects of their excessive consumption have also become evident. Acrylamide (AA), a processing hazard present in UPFs, can further aggravate the harmful effects of UPFs. AA can cause significant damage to both the intestinal barrier and gut microbiota, thereby affecting the nervous system through the microbiota-gut-brain (MGB) axis. Natural polysaccharides have demonstrated the capacity to significantly alleviate the oxidative stress and inflammatory response associated with AA exposure. In addition, they exhibit neuroprotective properties that may be mediated through the MGB axis. This paper reviews literature on the presence of AA in certain UPFs and its potential to inflict serious harm on the human gut microbiota and brain. Moreover, the possibility of utilizing polysaccharides as a preventative measure against AA-induced neurotoxicity was also proposed. These findings provide new insights into the safety risks associated with the overconsumption of UPFs and highlight the potential of polysaccharides to counteract the neurodegeneration induced by AA.
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Affiliation(s)
- Chen Cai
- College of Food Science and Nutritional Engineering, National Engineering Research Centre for Fruits and Vegetables Processing, Key Laboratory of Storage and Processing of Fruits and Vegetables, Ministry of Agriculture, Engineering Research Centre for Fruits and Vegetables Processing, Ministry of Education, China Agricultural University, Beijing 100083, P.R. China.
| | - Zheyi Song
- Department of Food Science and Engineering, Ningbo University, Ningbo 315211, P.R. China.
| | - Xinrui Xu
- College of Food Science and Nutritional Engineering, National Engineering Research Centre for Fruits and Vegetables Processing, Key Laboratory of Storage and Processing of Fruits and Vegetables, Ministry of Agriculture, Engineering Research Centre for Fruits and Vegetables Processing, Ministry of Education, China Agricultural University, Beijing 100083, P.R. China.
| | - Xin Yang
- College of Food Science and Nutritional Engineering, National Engineering Research Centre for Fruits and Vegetables Processing, Key Laboratory of Storage and Processing of Fruits and Vegetables, Ministry of Agriculture, Engineering Research Centre for Fruits and Vegetables Processing, Ministry of Education, China Agricultural University, Beijing 100083, P.R. China.
| | - Siyu Wei
- College of Food Science and Nutritional Engineering, National Engineering Research Centre for Fruits and Vegetables Processing, Key Laboratory of Storage and Processing of Fruits and Vegetables, Ministry of Agriculture, Engineering Research Centre for Fruits and Vegetables Processing, Ministry of Education, China Agricultural University, Beijing 100083, P.R. China.
| | - Fang Chen
- College of Food Science and Nutritional Engineering, National Engineering Research Centre for Fruits and Vegetables Processing, Key Laboratory of Storage and Processing of Fruits and Vegetables, Ministry of Agriculture, Engineering Research Centre for Fruits and Vegetables Processing, Ministry of Education, China Agricultural University, Beijing 100083, P.R. China.
| | - Xu Dong
- Department of Gynaecology, Beilun People's Hospital, Ningbo 315800, P.R. China
| | - Xin Zhang
- Department of Food Science and Engineering, Ningbo University, Ningbo 315211, P.R. China.
| | - Yuchen Zhu
- College of Food Science and Nutritional Engineering, National Engineering Research Centre for Fruits and Vegetables Processing, Key Laboratory of Storage and Processing of Fruits and Vegetables, Ministry of Agriculture, Engineering Research Centre for Fruits and Vegetables Processing, Ministry of Education, China Agricultural University, Beijing 100083, P.R. China.
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Kabir H, Mahdavi SS, Abdekhodaie MJ, Rafii AB, Merati M. Development of an in-situ forming collagen-based hydrogel as a regenerative bioadhesive for corneal perforations. Int J Biol Macromol 2024; 278:134761. [PMID: 39151870 DOI: 10.1016/j.ijbiomac.2024.134761] [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: 01/11/2024] [Revised: 07/17/2024] [Accepted: 08/13/2024] [Indexed: 08/19/2024]
Abstract
Corneal injuries play a significant role in global visual impairment, underscoring the demand for innovative biomaterials with specific attributes such as adhesion, cohesion, and regenerative potential. In this study, we have developed a biocompatible bioadhesive for corneal reconstruction. Derived from Collagen type I, naturally present in human corneal stromal tissue, the bioadhesive was cross-linked with modified polyethylene glycol diacrylate (PEGDA-DOPA), rendering it curable through visible light exposure and exhibiting superior adhesion to biological tissues even in wet conditions. The physicochemical characteristics of the proposed bioadhesive were customized by manipulating the concentration of its precursor polymers and adjusting the duration of photocrosslinking. To identify the optimal sample with maximum adhesion, mechanical strength, and biocompatibility, characterization tests were conducted. The optimal specimen, consisting of 30 % (w/v) PEGDA-DOPA and cured with visible light for 5 min, exhibited commendable adhesive strength of 783.6 kPa and shear strength of 53.7 kPa, surpassing that of commercialized eye adhesives.Additionally, biocompatibility test results indicated a notably high survival rate (>100 %) of keratocytes seeded on the hydrogel adhesive after 7 days of incubation. Consequently, this designed bioadhesive, characterized by high adhesion strength, robust mechanical strength, and excellent biocompatibility, is anticipated to enhance the spontaneous repair process of damaged corneal stromal tissue.
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Affiliation(s)
- Hannaneh Kabir
- Cellular and Molecular Biomechanics Lab, Department of Bioengineering, University of California at Berkeley, California, USA; Department of Chemical Engineering, Sharif University of Technology, Tehran, Iran.
| | - S Sharareh Mahdavi
- Research Operations, The Hospital for Sick Children, Toronto, Canada; Department of Chemical Engineering, Sharif University of Technology, Tehran, Iran
| | - Mohammad Jafar Abdekhodaie
- Environmental and Applied Science Management, Yeates School of Graduate Studies, Toronto Metropolitan University, Toronto, Canada; Department of Chemical Engineering, Sharif University of Technology, Tehran, Iran.
| | - Alireza Baradaran Rafii
- Department of Ophthalmology, Morsani College of Medicine, University of South Florida, Tampa, Florida, USA
| | - Mohsen Merati
- Division of Gastroenterology, Department of Medicine, University of California at San Francisco, California, USA
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Chang C, Liu H, Li X, Song D, Liu Y, Lu C, Zhen Y, Chen Y, Xu J, Li W, Jia X, Chen Z, Chen R. Combined ROS Responsive Polydopamine-Coated Berberine Nanoparticles Effective Against Ulcerative Colitis in Mouse Model. Int J Nanomedicine 2024; 19:1205-1224. [PMID: 38348171 PMCID: PMC10860565 DOI: 10.2147/ijn.s442761] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/01/2023] [Accepted: 01/30/2024] [Indexed: 02/15/2024] Open
Abstract
Introduction Enhancing the efficacy of berberine (BBR) in the treatment of ulcerative colitis (UC) through the development of dopamine-coated berberine nanoparticles (PDA@BBR NPs) with ROS-responsive and adhesive properties. Methods Berberine nanoparticles (BBR NPs) were synthesized using the nonsolvent precipitation method, and their surfaces were coated with polydopamine (PDA) through oxidative polymerization. The PDA@BBR NPs were characterized by transmission electron microscopy (TEM), size analysis, and zeta potential analysis. Drug loading and encapsulation efficiency were analyzed using fluorescence spectroscopy. The responsiveness of these nanoparticles to reactive oxygen species (ROS) was assessed in vitro, while their adhesive properties and therapeutic efficacy on UC were evaluated in vivo. Results Physicochemical property studies showed that PDA coated BBR NPs nanoparticles have good dispersion and stability. In vitro results showed that PDA@BBR NPs could prolong the retention time of the drug at the colonic site and could realize the gradual drug release under ROS environment. In addition, animal studies showed that PDA@BBR NPs exhibited significant anti-inflammatory effects on DSS-induced colitis and effectively reduced intestinal mucosal damage. Conclusion PDA@BBR NPs are ROS-responsive nanoparticles that adhere well and have a high drug loading capacity. They have shown therapeutic effects in mice with UC, indicating that this formulation may be a promising treatment option.
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Affiliation(s)
- Chenqi Chang
- School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, 210023, People’s Republic of China
| | - Heng Liu
- Yunnan Provincial Key Laboratory of Entomological Biopharmaceutical R&D, College of Pharmacy, Dali University, Dali, 671003, People’s Republic of China
| | - Xiaotong Li
- Yunnan Provincial Key Laboratory of Entomological Biopharmaceutical R&D, College of Pharmacy, Dali University, Dali, 671003, People’s Republic of China
| | - Dandan Song
- School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, 210023, People’s Republic of China
| | - Yue Liu
- School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, 210023, People’s Republic of China
| | - Chang Lu
- School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, 210023, People’s Republic of China
| | - Yu Zhen
- School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, 210023, People’s Republic of China
| | - Ying Chen
- School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, 210023, People’s Republic of China
| | - Jinguo Xu
- School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, 210023, People’s Republic of China
| | - Weidong Li
- School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, 210023, People’s Republic of China
| | - Xiaobin Jia
- School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing, 211198, People’s Republic of China
| | - Zhipeng Chen
- School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, 210023, People’s Republic of China
| | - Rui Chen
- School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, 210023, People’s Republic of China
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Guo Y, Zeng X, Li J, Yuan H, Lan J, Yu Y, Yang X. A high performance composite separator with robust environmental stability for dendrite-free lithium metal batteries. J Colloid Interface Sci 2023; 642:321-329. [PMID: 37011450 DOI: 10.1016/j.jcis.2023.03.149] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/22/2022] [Revised: 03/22/2023] [Accepted: 03/23/2023] [Indexed: 03/31/2023]
Abstract
The garnet ceramic Li6.4La3Zr1.4Ta0.6O12 (LLZTO) modified separators have been proposed to overcome the poor thermal stability and wettability of commercial polyolefin separators. However, the side reaction of LLZTO in the air leads to deterioration of environmental stability of composite separators (PP-LLZTO), which will limit the electrochemical performance of batteries. Herein, the LLZTO with the polydopamine (PDA) coating (LLZTO@PDA) was prepared by solution oxidation, and then applied it to a commercial polyolefin separator to achieve a composite separator (PP-LLZTO@PDA). LLZTO@PDA is stable in the air, and no Li2CO3 can be observed on the surface even after 90 days in the air. Besides, LLZTO@PDA coating endows the PP-LLZTO@PDA separator with the tensile strength (up to 103 MPa), good wettability (contact angle 0°) and high ionic conductivity (0.93 mS cm-1). Consequently, the Li/PP-LLZTO@PDA/Li symmetric cell cycles stably for 600 h without significant dendrites generation, and the assembled Li//LFP cells with PP-LLZTO@PDA-D30 separators deliver a high capacity retention of 91.8% after 200 cycles at 0.1C. This research provides a practical strategy for constructing composite separators with excellent environmental stability and high electrochemical properties.
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Attia MS, Yahya A, Monaem NA, Sabry SA. Mesoporous silica nanoparticles: Their potential as drug delivery carriers and nanoscavengers in Alzheimer's and Parkinson's diseases. Saudi Pharm J 2023; 31:417-432. [PMID: 37026045 PMCID: PMC10071366 DOI: 10.1016/j.jsps.2023.01.009] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/28/2022] [Accepted: 01/25/2023] [Indexed: 02/04/2023] Open
Abstract
Worldwide, populations face significant burdens from neurodegenerative disorders (NDDs), especially Alzheimer's and Parkinson's diseases. Although there are many proposed etiologies for neurodegenerative disorders, including genetic and environmental factors, the exact pathogenesis for these disorders is not fully understood. Most patients with NDDs are given lifelong treatment to improve their quality of life. There are myriad treatments for NDDs; however, these agents are limited by their side effects and difficulty in passing the blood-brain barrier (BBB). Furthermore, the central nervous system (CNS) active pharmaceuticals could offer symptomatic relief for the patient's condition without providing a complete cure or prevention by targeting the disease's cause. Recently, Mesoporous silica nanoparticles (MSNs) have gained interest in treating NDDs since their physicochemical properties and inherent ability to pass BBB make them possible drug carriers for several drugs for NDDs treatment. This paper provides insight into the pathogenesis and treatment of NDDs, along with the recent advances in applying MSNs as fibril scavengers. Moreover, the application of MSNs-based formulations in enhancing or sustaining drug release rate, and brain targeting via their responsive release properties, besides the neurotoxicity of MSNs, have been reviewed.
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Affiliation(s)
- Mohamed S. Attia
- Department of Pharmaceutics, Faculty of Pharmacy, Zagazig University, Zagazig 44519, Egypt
- Corresponding author.
| | - Ahmed Yahya
- Egypt-Japan University of Science and Technology, New Borg El Arab, Alexandria 21934, Egypt
| | - Nada Abdel Monaem
- Department of chemistry, Faculty of Science, Zagazig University, Zagazig 44519, Egypt
| | - Shereen A. Sabry
- Department of Pharmaceutics, Faculty of Pharmacy, Zagazig University, Zagazig 44519, Egypt
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Paccione N, Rahmani M, Barcia E, Negro S. Antiparkinsonian Agents in Investigational Polymeric Micro- and Nano-Systems. Pharmaceutics 2022; 15:pharmaceutics15010013. [PMID: 36678642 PMCID: PMC9866990 DOI: 10.3390/pharmaceutics15010013] [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: 09/29/2022] [Revised: 12/13/2022] [Accepted: 12/15/2022] [Indexed: 12/24/2022] Open
Abstract
Parkinson's disease (PD) is a devastating neurodegenerative disease characterized by progressive destruction of dopaminergic tissue in the central nervous system (CNS). To date, there is no cure for the disease, with current pharmacological treatments aimed at controlling the symptoms. Therefore, there is an unmet need for new treatments for PD. In addition to new therapeutic options, there exists the need for improved efficiency of the existing ones, as many agents have difficulties in crossing the blood-brain barrier (BBB) to achieve therapeutic levels in the CNS or exhibit inappropriate pharmacokinetic profiles, thereby limiting their clinical benefits. To overcome these limitations, an interesting approach is the use of drug delivery systems, such as polymeric microparticles (MPs) and nanoparticles (NPs) that allow for the controlled release of the active ingredients targeting to the desired site of action, increasing the bioavailability and efficacy of treatments, as well as reducing the number of administrations and adverse effects. Here we review the polymeric micro- and nano-systems under investigation as potential new therapies for PD.
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Affiliation(s)
- Nicola Paccione
- Department of Pharmaceutics and Food Technology, School of Pharmacy, Universidad Complutense de Madrid, Ciudad Universitaria s/n, 28040 Madrid, Spain
| | - Mahdieh Rahmani
- Department of Pharmaceutics and Food Technology, School of Pharmacy, Universidad Complutense de Madrid, Ciudad Universitaria s/n, 28040 Madrid, Spain
- Correspondence: ; Tel.: +34-913941741
| | - Emilia Barcia
- Department of Pharmaceutics and Food Technology, School of Pharmacy, Universidad Complutense de Madrid, Ciudad Universitaria s/n, 28040 Madrid, Spain
- Institute of Industrial Pharmacy, Universidad Complutense de Madrid, Ciudad Universitaria s/n, 28040 Madrid, Spain
| | - Sofía Negro
- Department of Pharmaceutics and Food Technology, School of Pharmacy, Universidad Complutense de Madrid, Ciudad Universitaria s/n, 28040 Madrid, Spain
- Institute of Industrial Pharmacy, Universidad Complutense de Madrid, Ciudad Universitaria s/n, 28040 Madrid, Spain
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Wang X, Zhang Z, Hadjichristidis N. Poly(amino ester)s as an emerging synthetic biodegradable polymer platform: Recent developments and future trends. Prog Polym Sci 2022. [DOI: 10.1016/j.progpolymsci.2022.101634] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022]
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9
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Yang W, Zeng Q, Pan Q, Huang W, Hu H, Shao Z. Application and prospect of ROS-related nanomaterials for orthopaedic related diseases treatment. Front Chem 2022; 10:1035144. [PMID: 36277336 PMCID: PMC9581401 DOI: 10.3389/fchem.2022.1035144] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/02/2022] [Accepted: 09/16/2022] [Indexed: 11/13/2022] Open
Abstract
The importance of reactive oxygen species (ROS) in the occurrence and development of orthopaedic related diseases is becoming increasingly prominent. ROS regulation has become a new method to treat orthopaedic related diseases. In recent years, the application of nanomaterials has become a new hope for precision and efficient treatment. However, there is a lack of reviews on ROS-regulated nanomaterials for orthopaedic related diseases. Based on the key significance of nanomaterials for the treatment of orthopaedic related diseases, we searched the latest related studies and reviewed the nanomaterials that regulate ROS in the treatment of orthopaedic related diseases. According to the function of nanomaterials, we describe the scavenging of ROS related nanomaterials and the generation of ROS related nanomaterials. In this review, we closely integrated nanomaterials with the treatment of orthopaedic related diseases such as arthritis, osteoporosis, wound infection and osteosarcoma, etc., and highlighted the advantages and disadvantages of existing nanomaterials. We also looked forward to the design of ROS-regulated nanomaterials for the treatment of orthopaedic related diseases in the future.
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Affiliation(s)
- Wenbo Yang
- Department of Orthopaedic Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Qianwen Zeng
- School of Nursing, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Qing Pan
- Department of Orthopaedic Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Wei Huang
- Department of Orthopaedic Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- *Correspondence: Zengwu Shao, ; Hongzhi Hu, ; Wei Huang,
| | - Hongzhi Hu
- Department of Orthopaedic Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- *Correspondence: Zengwu Shao, ; Hongzhi Hu, ; Wei Huang,
| | - Zengwu Shao
- Department of Orthopaedic Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- *Correspondence: Zengwu Shao, ; Hongzhi Hu, ; Wei Huang,
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Newland B, Starke J, Bastiancich C, Gonçalves DPN, Bray LJ, Wang W, Werner C. Well-Defined Polyethylene Glycol Microscale Hydrogel Blocks Containing Gold Nanorods for Dual Photothermal and Chemotherapeutic Therapy. Pharmaceutics 2022; 14:551. [PMID: 35335927 PMCID: PMC8954019 DOI: 10.3390/pharmaceutics14030551] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/17/2022] [Revised: 02/11/2022] [Accepted: 02/14/2022] [Indexed: 01/27/2023] Open
Abstract
Local drug delivery offers a means of achieving a high concentration of therapeutic agents directly at the tumor site, whilst minimizing systemic toxicity. For heterogenous cancers such as glioblastoma, multimodal therapeutic approaches hold promise for better efficacy. Herein, we aimed to create a well-defined and reproducible drug delivery system that also incorporates gold nanorods for photothermal therapy. Solvent-assisted micromolding was used to create uniform sacrificial templates in which microscale hydrogels were formed with and without gold nanorods throughout their structure. The microscale hydrogels could be loaded with doxorubicin, releasing it over a period of one week, causing toxicity to glioma cells. Since these microscale hydrogels were designed for direct intratumoral injection, therefore bypassing the blood-brain barrier, the highly potent breast cancer therapeutic doxorubicin was repurposed for use in this study. By contrast, the unloaded hydrogels were well tolerated, without decreasing cell viability. Irradiation with near-infrared light caused heating of the hydrogels, showing that if concentrated at an injection site, these hydrogels maybe able to cause anticancer activity through two separate mechanisms.
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Affiliation(s)
- Ben Newland
- Leibniz-Institut für Polymerforschung Dresden e.V., Max Bergmann Center of Biomaterials Dresden, Hohe Str. 6, 01069 Dresden, Germany; (J.S.); (L.J.B.); (C.W.)
- School of Pharmacy and Pharmaceutical Sciences, Cardiff University, Cardiff CF10 3NB, UK
| | - Johannes Starke
- Leibniz-Institut für Polymerforschung Dresden e.V., Max Bergmann Center of Biomaterials Dresden, Hohe Str. 6, 01069 Dresden, Germany; (J.S.); (L.J.B.); (C.W.)
| | - Chiara Bastiancich
- Aix-Marseille Univ, CNRS, INP, Inst Neurophysiopathol, 13344 Marseille, France;
| | - Diana P. N. Gonçalves
- Department of Chemistry and Biochemistry, Kent State University, Kent, OH 44242, USA;
| | - Laura J. Bray
- Leibniz-Institut für Polymerforschung Dresden e.V., Max Bergmann Center of Biomaterials Dresden, Hohe Str. 6, 01069 Dresden, Germany; (J.S.); (L.J.B.); (C.W.)
| | - Wenxin Wang
- Charles Institute of Dermatology, School of Medicine, University College Dublin, Belfield, D04 V1W8 Dublin, Ireland;
| | - Carsten Werner
- Leibniz-Institut für Polymerforschung Dresden e.V., Max Bergmann Center of Biomaterials Dresden, Hohe Str. 6, 01069 Dresden, Germany; (J.S.); (L.J.B.); (C.W.)
- Center for Regenerative Therapies Dresden and Cluster of Excellence Physics of Life, Technische Universität Dresden, 01062 Dresden, Germany
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11
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Li L, Peng H, Du Y, Zheng H, Yang A, Lv G, Li H. An antibacterial biomimetic adhesive with strong adhesion in both dry and underwater situations. J Mater Chem B 2022; 10:1063-1076. [PMID: 35076052 DOI: 10.1039/d1tb02215f] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Abstract
Adhesives have attracted extensive attention in biomedical applications in recent years. However, the development of adhesives with strong adhesion in both dry and underwater conditions and antibacterial properties is still a challenge. Herein, a biomimetic adhesive (DP@TA/Gel) was developed based on the adhesion mechanism of mussel in water, from adhesion and solidification to avoiding excessive oxidization processes. DP@TA/Gel exhibited rapid strong nonspecific adhesiveness to diverse materials including wood (485 kPa) metal (507 kPa), plastic (74 kPa), and even fresh biological tissue (39 kPa) in dry conditions. Specially, owing to its biomimetic design, DP@TA/Gel could imitate the mussel adhesion mechanism underwater, endowing it with robust (38 kPa), highly repeatable (at least 15 times) and long-term (at least 120 h) stable adhesion even in underwater conditions. Remarkably, DP@TA/Gel also exhibited high adhesiveness in various water environments, including seawater, and a wide range of pH (3-11) and NaCl concentration (0.9-10%) solutions without any stimulus. In addition, DP@TA/Gel showed excellent biocompatibility and antibacterial properties. Thus, the DP@TA/Gel adhesive has appealing potential biomedical applications such as sutureless wound closure and as a tissue adhesive.
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Affiliation(s)
- Lin Li
- College of Physics, Sichuan University, Chengdu 610065, China.
| | - Haitao Peng
- College of Physics, Sichuan University, Chengdu 610065, China.
| | - Yan Du
- College of Physics, Sichuan University, Chengdu 610065, China.
| | - Heng Zheng
- College of Physics, Sichuan University, Chengdu 610065, China.
| | - Aiping Yang
- College of Physics, Sichuan University, Chengdu 610065, China.
| | - Guoyu Lv
- College of Physics, Sichuan University, Chengdu 610065, China.
| | - Hong Li
- College of Physics, Sichuan University, Chengdu 610065, China.
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12
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He Z, Xu Q, Newland B, Foley R, Lara-Sáez I, Curtin JF, Wang W. Reactive oxygen species (ROS): utilizing injectable antioxidative hydrogels and ROS-producing therapies to manage the double-edged sword. J Mater Chem B 2021; 9:6326-6346. [PMID: 34304256 DOI: 10.1039/d1tb00728a] [Citation(s) in RCA: 53] [Impact Index Per Article: 13.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
Reactive oxygen species (ROS) are generated in cellular metabolism and are essential for cellular signalling networks and physiological functions. However, the functions of ROS are 'double-edged swords' to living systems that have a fragile redox balance between ROS generation and elimination. A modest increase of ROS leads to enhanced cell proliferation, survival and benign immune responses, whereas ROS stress that overwhelms the cellular antioxidant capacity can damage nucleic acids, proteins and lipids, resulting in oncogenic mutations and cell death. ROS are therefore involved in many pathological conditions. On the other hand, ROS present selective toxicity and have been utilised against cancer and pathogens, thus also acting as a double-edged sword in the healthcare field. Injectable antioxidative hydrogels are gel precursors that form hydrogel constructs in situ upon delivery in vivo to maintain an antioxidative capacity. These hydrogels have been developed to counter ROS-induced pathological conditions, with significant advantages of biocompatibility, excellent moldability, and minimally invasive delivery. The intrinsic, readily controllable ROS-scavenging ability of the functionalised hydrogels overcomes many drawbacks of small molecule antioxidants. This review summarises the roles of ROS under pathological conditions and describes the state-of-the-art of injectable antioxidative hydrogels. A particular emphasis is also given to current ROS-producing therapeutic interventions, enabling potential application of injectable antioxidant hydrogels to prevent the adverse effects of many cancer and infection treatments.
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Affiliation(s)
- Zhonglei He
- Charles Institute of Dermatology, School of Medicine, University College Dublin, Dublin, Ireland.
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13
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Wang L, Zhu B, Deng Y, Li T, Tian Q, Yuan Z, Ma L, Cheng C, Guo Q, Qiu L. Biocatalytic and Antioxidant Nanostructures for ROS Scavenging and Biotherapeutics. ADVANCED FUNCTIONAL MATERIALS 2021. [DOI: 10.1002/adfm.202101804] [Citation(s) in RCA: 77] [Impact Index Per Article: 19.3] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/05/2023]
Affiliation(s)
- Liyun Wang
- Department of Ultrasound National Clinical Research Center for Geriatrics West China Hospital College of Polymer Science and Engineering Sichuan University Chengdu 610041 China
| | - Bihui Zhu
- Department of Ultrasound National Clinical Research Center for Geriatrics West China Hospital College of Polymer Science and Engineering Sichuan University Chengdu 610041 China
| | - Yuting Deng
- Department of Ultrasound National Clinical Research Center for Geriatrics West China Hospital College of Polymer Science and Engineering Sichuan University Chengdu 610041 China
| | - Tiantian Li
- Department of Ultrasound National Clinical Research Center for Geriatrics West China Hospital College of Polymer Science and Engineering Sichuan University Chengdu 610041 China
| | - Qinyu Tian
- Institute of Orthopedics The First Medical Center Chinese PLA General Hospital Beijing Key Lab of Regenerative Medicine in Orthopedics Key Laboratory of Musculoskeletal Trauma and War Injuries PLA No. 28 Fuxing Road, Haidian District Beijing 100853 China
| | - Zhiguo Yuan
- Institute of Orthopedics The First Medical Center Chinese PLA General Hospital Beijing Key Lab of Regenerative Medicine in Orthopedics Key Laboratory of Musculoskeletal Trauma and War Injuries PLA No. 28 Fuxing Road, Haidian District Beijing 100853 China
| | - Lang Ma
- Department of Ultrasound National Clinical Research Center for Geriatrics West China Hospital College of Polymer Science and Engineering Sichuan University Chengdu 610041 China
| | - Chong Cheng
- Department of Ultrasound National Clinical Research Center for Geriatrics West China Hospital College of Polymer Science and Engineering Sichuan University Chengdu 610041 China
- State Key Laboratory of Polymer Materials Engineering Sichuan University Chengdu 610064 China
- Department of Chemistry and Biochemistry Freie Universität Berlin Takustrasse 3 Berlin 14195 Germany
| | - Quanyi Guo
- Institute of Orthopedics The First Medical Center Chinese PLA General Hospital Beijing Key Lab of Regenerative Medicine in Orthopedics Key Laboratory of Musculoskeletal Trauma and War Injuries PLA No. 28 Fuxing Road, Haidian District Beijing 100853 China
| | - Li Qiu
- Department of Ultrasound National Clinical Research Center for Geriatrics West China Hospital College of Polymer Science and Engineering Sichuan University Chengdu 610041 China
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14
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Newland B, Newland H, Lorenzi F, Eigel D, Welzel PB, Fischer D, Wang W, Freudenberg U, Rosser A, Werner C. Injectable Glycosaminoglycan-Based Cryogels from Well-Defined Microscale Templates for Local Growth Factor Delivery. ACS Chem Neurosci 2021; 12:1178-1188. [PMID: 33754692 PMCID: PMC8033563 DOI: 10.1021/acschemneuro.1c00005] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
![]()
Glycosaminoglycan-based hydrogels
hold great potential for applications
in tissue engineering and regenerative medicine. By mimicking the
natural extracellular matrix processes of growth factor binding and
release, such hydrogels can be used as a sustained delivery device
for growth factors. Since neural networks commonly follow well-defined,
high-aspect-ratio paths through the central and peripheral nervous
system, we sought to create a fiber-like, elongated growth factor
delivery system. Cryogels, with networks formed at subzero temperatures,
are well-suited for the creation of high-aspect-ratio biomaterials,
because they have a macroporous structure making them mechanically
robust (for ease of handling) yet soft and highly compressible (for
interfacing with brain tissue). Unlike hydrogels, cryogels can be
synthesized in advance of their use, stored with ease, and rehydrated
quickly to their original shape. Herein, we use solvent-assisted microcontact
molding to form sacrificial templates, in which we produced highly
porous cryogel microscale scaffolds with a well-defined elongated
shape via the photopolymerization of poly(ethylene glycol) diacrylate
and maleimide-functionalized heparin. Dissolution of the template
yielded cryogels that could load nerve growth factor (NGF) and release
it over a period of 2 weeks, causing neurite outgrowth in PC12 cell
cultures. This microscale template-assisted synthesis technique allows
tight control over the cryogel scaffold dimensions for high reproducibility
and ease of injection through fine gauge needles.
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Affiliation(s)
- Ben Newland
- Leibniz-Institut für Polymerforschung Dresden e.V., Max Bergmann Center of Biomaterials Dresden, Hohe Straße 6, D-01069 Dresden, Germany
- School of Pharmacy and Pharmaceutical Sciences, Cardiff University, King Edward VII Avenue, Cardiff CF10 3NB, U.K
| | - Heike Newland
- Leibniz-Institut für Polymerforschung Dresden e.V., Max Bergmann Center of Biomaterials Dresden, Hohe Straße 6, D-01069 Dresden, Germany
| | - Francesca Lorenzi
- Leibniz-Institut für Polymerforschung Dresden e.V., Max Bergmann Center of Biomaterials Dresden, Hohe Straße 6, D-01069 Dresden, Germany
- Dipartimento di Scienze Chimiche, Università degli Studi di Padova, via Francesco Marzolo, 135131 Padova, Italy
| | - Dimitri Eigel
- Leibniz-Institut für Polymerforschung Dresden e.V., Max Bergmann Center of Biomaterials Dresden, Hohe Straße 6, D-01069 Dresden, Germany
| | - Petra B. Welzel
- Leibniz-Institut für Polymerforschung Dresden e.V., Max Bergmann Center of Biomaterials Dresden, Hohe Straße 6, D-01069 Dresden, Germany
| | - Dieter Fischer
- Leibniz-Institut für Polymerforschung Dresden e.V., Max Bergmann Center of Biomaterials Dresden, Hohe Straße 6, D-01069 Dresden, Germany
| | - Wenxin Wang
- Charles Institute for Dermatology, University College Dublin, Dublin D04 V1W8, Ireland
| | - Uwe Freudenberg
- Leibniz-Institut für Polymerforschung Dresden e.V., Max Bergmann Center of Biomaterials Dresden, Hohe Straße 6, D-01069 Dresden, Germany
| | - Anne Rosser
- Brain Repair Group, School of Biosciences, Cardiff University, Cardiff CF10 3AX, U.K
- Brain Repair And Intracranial Neurotherapeutics (BRAIN) Unit, Neuroscience and Mental Health Research Institute, Cardiff University, Hadyn Ellis
Building, Maindy Road, Cardiff CF24 4HQ3, U.K
| | - Carsten Werner
- Leibniz-Institut für Polymerforschung Dresden e.V., Max Bergmann Center of Biomaterials Dresden, Hohe Straße 6, D-01069 Dresden, Germany
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15
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Yeo J, Lee J, Lee S, Kim WJ. Polymeric Antioxidant Materials for Treatment of Inflammatory Disorders. ADVANCED THERAPEUTICS 2021. [DOI: 10.1002/adtp.202000270] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Affiliation(s)
- Jiwon Yeo
- Department of Chemistry Pohang University of Science and Technology (POSTECH) Pohang 37673 Republic of Korea
| | - Junseok Lee
- Department of Chemistry Pohang University of Science and Technology (POSTECH) Pohang 37673 Republic of Korea
- OmniaMed Co, Ltd Pohang 37673 Republic of Korea
| | - Sanggi Lee
- School of Interdisciplinary Bioscience and Bioengineering (I‐Bio) Pohang University of Science and Technology (POSTECH) Pohang 37673 Republic of Korea
| | - Won Jong Kim
- Department of Chemistry Pohang University of Science and Technology (POSTECH) Pohang 37673 Republic of Korea
- OmniaMed Co, Ltd Pohang 37673 Republic of Korea
- School of Interdisciplinary Bioscience and Bioengineering (I‐Bio) Pohang University of Science and Technology (POSTECH) Pohang 37673 Republic of Korea
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16
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Chen T, Yang Y, Zhu S, Lu Y, Zhu L, Wang Y, Wang X. Inhibition of Aβ aggregates in Alzheimer's disease by epigallocatechin and epicatechin-3-gallate from green tea. Bioorg Chem 2020; 105:104382. [PMID: 33137558 DOI: 10.1016/j.bioorg.2020.104382] [Citation(s) in RCA: 26] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/25/2020] [Revised: 10/11/2020] [Accepted: 10/13/2020] [Indexed: 02/02/2023]
Abstract
Alzheimer's disease (AD) is a neurodegenerative disorder characterized by progressive accumulation of senile plaques, which are primarily composed of misfolded amyloid β-peptide (Aβ). Aβ aggregates are believed to be a key factor in the pathogenesis of AD, affecting the nervous system in human body. The therapeutic potential of tea-derived polyphenolic compounds, (-)-epigallocatechin (EGC) and (-)-epicatechin-3-gallate (ECG), for AD was investigated by assessing their effects on the Cu2+/Zn2+-induced or self-assembled Aβ40 aggregation using thioflavine T fluorescent spectrometry, inductively coupled plasma mass spectrometry, UV-Vis spectroscopy, transmission electron microscope, silver staining, immunohistochemistry, and immunofluorescence assays. EGC and ECG mildly bind to Cu2+ and Zn2+, and diminish the Cu2+- or Zn2+-induced or self-assembled Aβ aggregates; they also modulate the Cu2+/Zn2+-Aβ40 induced neurotoxicity on mouse neuroblastoma Neuro-2a cells by reducing the production of ROS. Metal chelating, hydrogen bonding or Van Der Waals force may drive the interaction between the polyphenolic compounds and Aβ. The results demonstrate that green tea catechins EGC and ECG are able to alleviate the toxicity of Aβ oligomers and fibrils. Particularly, ECG can cross the blood-brain barrier to reduce the Aβ plaques in the brain of APP/PS1 mice, thereby protecting neurons from injuries. The results manifest the potential of green tea for preventing or ameliorating the symptoms of AD.
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Affiliation(s)
- Tingting Chen
- School of Chemistry and Chemical Engineering, Nantong University, Nantong 226019, PR China
| | - Yanfei Yang
- Institute of Nautical Medicine, Nantong University, Nantong 226019, PR China
| | - Shajun Zhu
- Department of General Surgery, Affiliated Hospital of Nantong University, Nantong 226001, PR China
| | - Yapeng Lu
- Institute of Nautical Medicine, Nantong University, Nantong 226019, PR China
| | - Li Zhu
- Institute of Nautical Medicine, Nantong University, Nantong 226019, PR China.
| | - Yanqing Wang
- School of Chemistry and Chemical Engineering, Yancheng Teachers University, Yancheng 224002, PR China
| | - Xiaoyong Wang
- School of Life Sciences, Nanjing University, Nanjing 210023, PR China.
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17
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Bhagat AK, Buium H, Shmul G, Alfonta L. Genetically Expanded Reactive-Oxygen-Tolerant Alcohol Dehydrogenase II. ACS Catal 2020. [DOI: 10.1021/acscatal.9b03739] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/20/2023]
Affiliation(s)
- Ashok Kumar Bhagat
- Departments of Life Sciences, Chemistry and Ilse Katz Institute for Nanoscale Science and Technology, Ben-Gurion University of the Negev, Beer-Sheva 8410501, Israel
| | - Hadar Buium
- Departments of Life Sciences, Chemistry and Ilse Katz Institute for Nanoscale Science and Technology, Ben-Gurion University of the Negev, Beer-Sheva 8410501, Israel
| | - Guy Shmul
- Department of Chemical Research Support, Weizmann Institute of Science, Rehovot 7610001, Israel
| | - Lital Alfonta
- Departments of Life Sciences, Chemistry and Ilse Katz Institute for Nanoscale Science and Technology, Ben-Gurion University of the Negev, Beer-Sheva 8410501, Israel
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18
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An Z, Yan J, Zhang Y, Pei R. Applications of nanomaterials for scavenging reactive oxygen species in the treatment of central nervous system diseases. J Mater Chem B 2020; 8:8748-8767. [DOI: 10.1039/d0tb01380c] [Citation(s) in RCA: 20] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/28/2022]
Abstract
Nanomaterials with excellent ROS-scavenging ability and biodistribution are considered as promising candidates in alleviating oxidative stress and restoring redox balance in CNS diseases, further facilitating the function recovery of the CNS.
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Affiliation(s)
- Zhen An
- CAS Key Laboratory for Nano-Bio Interface
- Suzhou Institute of Nano-Tech and Nano-Bionics
- Chinese Academy of Sciences
- Suzhou
- China
| | - Jincong Yan
- CAS Key Laboratory for Nano-Bio Interface
- Suzhou Institute of Nano-Tech and Nano-Bionics
- Chinese Academy of Sciences
- Suzhou
- China
| | - Ye Zhang
- CAS Key Laboratory for Nano-Bio Interface
- Suzhou Institute of Nano-Tech and Nano-Bionics
- Chinese Academy of Sciences
- Suzhou
- China
| | - Renjun Pei
- CAS Key Laboratory for Nano-Bio Interface
- Suzhou Institute of Nano-Tech and Nano-Bionics
- Chinese Academy of Sciences
- Suzhou
- China
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19
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Bertoni S, Albertini B, Facchini C, Prata C, Passerini N. Glutathione-Loaded Solid Lipid Microparticles as Innovative Delivery System for Oral Antioxidant Therapy. Pharmaceutics 2019; 11:pharmaceutics11080364. [PMID: 31357663 PMCID: PMC6723327 DOI: 10.3390/pharmaceutics11080364] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/26/2019] [Revised: 07/23/2019] [Accepted: 07/25/2019] [Indexed: 01/16/2023] Open
Abstract
The present study aimed to develop a novel formulation containing glutathione (GSH) as an oral antioxidant therapy for the treatment of oxidative stress-related intestinal diseases. To this purpose, solid lipid microparticles (SLMs) with Dynasan 114 and a mixture of Dynasan 114 and Dynasan 118 were produced by spray congealing technology. The obtained SLMs had main particle sizes ranging from 250 to 355 µm, suitable for oral administration. GSH was efficiently loaded into the SLMs at 5% or 20% w/w and the encapsulation process did not modify its chemico-physical properties, as demonstrated by FT-IR, DSC and HSM analysis. Moreover, in vitro release studies using biorelevant media showed that Dynasan 114-based SLMs could efficiently release GSH in various intestinal fluids, while 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay demonstrated the good radical scavenging activity of this formulation. Dynasan 114-based SLMs exhibited an excellent biocompatibility on intestinal HT-29 cells at concentrations up to 2000 μg/mL. SLMs containing GSH alone or together with another antioxidant agent (catalase) were effective in reducing intracellular reactive oxygen species (ROS) levels. Overall, this study indicated that spray congealed SLMs are a promising oral drug delivery system for the encapsulation of one or more biological antioxidant agents for local intestinal treatment.
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Affiliation(s)
- Serena Bertoni
- Department of Pharmacy and BioTechnology, University of Bologna, Via S. Donato 19/2, 40127 Bologna, Italy
| | - Beatrice Albertini
- Department of Pharmacy and BioTechnology, University of Bologna, Via S. Donato 19/2, 40127 Bologna, Italy.
| | - Carlotta Facchini
- Department of Pharmacy and BioTechnology, University of Bologna, Via S. Donato 19/2, 40127 Bologna, Italy
| | - Cecilia Prata
- Department of Pharmacy and BioTechnology, University of Bologna, Via S. Donato 19/2, 40127 Bologna, Italy
| | - Nadia Passerini
- Department of Pharmacy and BioTechnology, University of Bologna, Via S. Donato 19/2, 40127 Bologna, Italy
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20
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Bingol B, Altuncu S, Duman FD, Ak A, Gulyuz U, Acar HY, Okay O, Avci D. One-Step Injectable and Bioreducible Poly(β-Amino Ester) Hydrogels as Controlled Drug Delivery Platforms. ACS APPLIED POLYMER MATERIALS 2019; 1:1724-1734. [DOI: 10.1021/acsapm.9b00287] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/06/2025]
Affiliation(s)
- Betul Bingol
- Department of Chemistry, Bogazici University, 34342 Bebek, Istanbul, Turkey
| | - Seckin Altuncu
- Department of Chemistry, Bogazici University, 34342 Bebek, Istanbul, Turkey
| | - Fatma Demir Duman
- Department of Chemistry, Koc University, 34450 Sariyer, Istanbul, Turkey
| | - Ayse Ak
- Department of Chemistry, Koc University, 34450 Sariyer, Istanbul, Turkey
| | - Umit Gulyuz
- Department of Chemistry, Istanbul Technical University, Maslak 34469, Istanbul, Turkey
- Department of Chemistry and Chemical Processing Technologies, Kirklareli University, Luleburgaz 39750, Kirklareli, Turkey
| | - Havva Yagci Acar
- Department of Chemistry, Koc University, 34450 Sariyer, Istanbul, Turkey
| | - Oguz Okay
- Department of Chemistry, Istanbul Technical University, Maslak 34469, Istanbul, Turkey
| | - Duygu Avci
- Department of Chemistry, Bogazici University, 34342 Bebek, Istanbul, Turkey
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21
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Pan HM, Chen S, Jang TS, Han WT, Jung HD, Li Y, Song J. Plant seed-inspired cell protection, dormancy, and growth for large-scale biofabrication. Biofabrication 2019; 11:025008. [PMID: 30708358 DOI: 10.1088/1758-5090/ab03ed] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/23/2022]
Abstract
Biofabrication technologies have endowed us with the capability to fabricate complex biological constructs. However, cytotoxic biofabrication conditions have been a major challenge for their clinical application, leading to a trade-off between cell viability and scalability of biofabricated constructs. Taking inspiration from nature, we proposed a cell protection strategy which mimicks the protected and dormant state of plant seeds in adverse external conditions and their germination in response to appropriate environmental cues. Applying this bioinspired strategy to biofabrication, we successfully preserved cell viability and enhanced the seeding of cell-laden biofabricated constructs via a cytoprotective pyrogallol (PG)-alginate encapsulation system. Our cytoprotective encapsulation technology utilizes PG-triggered sporulation and germination processes to preserve cells, is mechanically robust, chemically resistant, and highly customizable to adequately match cell protectability with cytotoxicity of biofabrication conditions. More importantly, the facile and tunable decapsulation of our PG-alginate system allows for effective germination of dormant cells, under typical culture conditions. With this approach, we have successfully achieved a biofabrication process which is reproducible, scalable, and provided a practical solution for off-the-shelf availability, shipping and temporary storage of fabricated bio-constructs.
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Affiliation(s)
- Houwen Matthew Pan
- School of Chemical and Biomedical Engineering, Nanyang Technological University, 70 Nanyang Drive, 639798, Singapore
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22
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Liu Y, Li Y, Keskin D, Shi L. Poly(β-Amino Esters): Synthesis, Formulations, and Their Biomedical Applications. Adv Healthc Mater 2019; 8:e1801359. [PMID: 30549448 DOI: 10.1002/adhm.201801359] [Citation(s) in RCA: 88] [Impact Index Per Article: 14.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/26/2018] [Revised: 12/04/2018] [Indexed: 12/12/2022]
Abstract
Poly(β-amino ester) (abbreviated as PBAE or PAE) refers to a polymer synthesized from an acrylate and an amine by Michael addition and has properties inherent to tertiary amines and esters, such as pH responsiveness and biodegradability. The versatility of building blocks provides a library of polymers with miscellaneous physicochemical and mechanical properties. When used alone or together with other materials, PBAEs can be fabricated into different formulations in order to fulfill various requirements in drug delivery (for instance, gene, anticancer drugs, and antimicrobials delivery) and natural complex mimicry (nanochaperones). This progress report discusses the recent developments in design, synthesis, formulations, and applications of PBAEs in biomedical fields and provides a perspective view for the future of the PBAEs.
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Affiliation(s)
- Yong Liu
- State Key Laboratory of Medicinal Chemical BiologyKey Laboratory of Functional Polymer MaterialsMinistry of EducationInstitute of Polymer ChemistryCollege of ChemistryNankai University Tianjin 300071 China
- Department of Biomedical EngineeringUniversity of Groningen and University Medical Center Groningen Antonius Deusinglaan 1 9713 AV Groningen The Netherlands
| | - Yuanfeng Li
- State Key Laboratory of Medicinal Chemical BiologyKey Laboratory of Functional Polymer MaterialsMinistry of EducationInstitute of Polymer ChemistryCollege of ChemistryNankai University Tianjin 300071 China
- Department of Biomedical EngineeringUniversity of Groningen and University Medical Center Groningen Antonius Deusinglaan 1 9713 AV Groningen The Netherlands
| | - Damla Keskin
- Department of Biomedical EngineeringUniversity of Groningen and University Medical Center Groningen Antonius Deusinglaan 1 9713 AV Groningen The Netherlands
| | - Linqi Shi
- State Key Laboratory of Medicinal Chemical BiologyKey Laboratory of Functional Polymer MaterialsMinistry of EducationInstitute of Polymer ChemistryCollege of ChemistryNankai University Tianjin 300071 China
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23
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Xu Q, Venet M, Wang W, Creagh-Flynn J, Wang X, Li X, Gao Y, Zhou D, Zeng M, Lara-Sáez I, A S, Tai H, Wang W. Versatile Hyperbranched Poly(β-hydrazide ester) Macromers as Injectable Antioxidative Hydrogels. ACS APPLIED MATERIALS & INTERFACES 2018; 10:39494-39504. [PMID: 30376290 DOI: 10.1021/acsami.8b15006] [Citation(s) in RCA: 32] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/08/2023]
Abstract
Synthetic reactive oxygen species (ROS)-responsive biomaterials have emerged as a useful platform for regulating critical aspects of ROS-induced pathologies and can improve such hostile microenvironments. Here, we report a series of new hyperbranched poly(β-hydrazide ester) macromers (HB-PBHEs) with disulfide moieties synthesized via an "A2 + B4" Michael addition approach. The three-dimensional structure of HB-PBHEs with multiacrylate end groups endows the macromers with rapid gelation capabilities to form (1) injectable hydrogels via cross-linking with thiolated hyaluronic acid and (2) robust UV-cross-linked hydrogels. The disulfide-containing macromers and hydrogels exhibit H2O2-responsive degradation compared with the counterparts synthesized by a dihydrazide monomer without disulfide moieties. The cell viability under a high ROS environment can be well-maintained under the protection of the disulfide containing hydrogels.
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Affiliation(s)
- Qian Xu
- Charles Institute of Dermatology, School of Medicine , University College Dublin , Belfield, Dublin 4 , Ireland
| | - Manon Venet
- Molecular and Cellular Biology, Specialty Skin Biology, Department of Biology , Claude Bernard University Lyon I , 69622 , France
| | - Wei Wang
- School of Materials Science and Engineering , Tianjin University , Tianjin 300350 , China
| | - Jack Creagh-Flynn
- Charles Institute of Dermatology, School of Medicine , University College Dublin , Belfield, Dublin 4 , Ireland
| | - Xi Wang
- Charles Institute of Dermatology, School of Medicine , University College Dublin , Belfield, Dublin 4 , Ireland
| | - Xiaolin Li
- Charles Institute of Dermatology, School of Medicine , University College Dublin , Belfield, Dublin 4 , Ireland
| | - Yongsheng Gao
- Charles Institute of Dermatology, School of Medicine , University College Dublin , Belfield, Dublin 4 , Ireland
| | - Dezhong Zhou
- Charles Institute of Dermatology, School of Medicine , University College Dublin , Belfield, Dublin 4 , Ireland
| | - Ming Zeng
- Charles Institute of Dermatology, School of Medicine , University College Dublin , Belfield, Dublin 4 , Ireland
| | - Irene Lara-Sáez
- Charles Institute of Dermatology, School of Medicine , University College Dublin , Belfield, Dublin 4 , Ireland
| | - Sigen A
- Charles Institute of Dermatology, School of Medicine , University College Dublin , Belfield, Dublin 4 , Ireland
| | - Hongyun Tai
- School of Chemistry , Bangor University , Bangor , Gwynedd LL57 2DG , U.K
| | - Wenxin Wang
- Charles Institute of Dermatology, School of Medicine , University College Dublin , Belfield, Dublin 4 , Ireland
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24
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Bingol HB, Demir Duman F, Yagci Acar H, Yagci MB, Avci D. Redox-responsive phosphonate-functionalized poly(β-amino ester) gels and cryogels. Eur Polym J 2018. [DOI: 10.1016/j.eurpolymj.2018.08.029] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/26/2023]
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25
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Newland H, Eigel D, Rosser AE, Werner C, Newland B. Oxygen producing microscale spheres affect cell survival in conditions of oxygen-glucose deprivation in a cell specific manner: implications for cell transplantation. Biomater Sci 2018; 6:2571-2577. [PMID: 30132477 PMCID: PMC6157640 DOI: 10.1039/c8bm00490k] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/03/2018] [Accepted: 06/27/2018] [Indexed: 12/31/2022]
Abstract
This study outlines the synthesis of microscale oxygen producing spheres, which, when used in conjunction with catalase, can raise the dissolved oxygen content of cell culture media for 16-20 hours. In conditions of oxygen and glucose deprivation, designed to mimic the graft environment in vivo, the spheres rescue SH-SY5Y cells and meschymal stem cells, showing that oxygen producing biomaterials may hold potential to improve the survival of cells post-transplantation.
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Affiliation(s)
- Heike Newland
- Leibniz Institute of Polymer Research Dresden (IPF)
,
Hohe Strasse 6
, 01069 Dresden
, Germany
| | - Dimitri Eigel
- Leibniz Institute of Polymer Research Dresden (IPF)
,
Hohe Strasse 6
, 01069 Dresden
, Germany
| | - Anne E. Rosser
- Brain Repair Group
, School of Biosciences
, Cardiff University
,
CF10 3AX
, UK
| | - Carsten Werner
- Leibniz Institute of Polymer Research Dresden (IPF)
,
Hohe Strasse 6
, 01069 Dresden
, Germany
| | - Ben Newland
- Leibniz Institute of Polymer Research Dresden (IPF)
,
Hohe Strasse 6
, 01069 Dresden
, Germany
- School of Pharmacy and Pharmaceutical Sciences
, Cardiff University
,
CF10 3NB
, UK
.
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Schneider T, Kubyshkin V, Budisa N. Synthesis of a Photo-Caged DOPA Derivative by Selective Alkylation of 3,4-Dihydroxybenzaldehyde. European J Org Chem 2018. [DOI: 10.1002/ejoc.201701749] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Affiliation(s)
- Tobias Schneider
- Institute of Chemistry; Technical University of Berlin; Müller-Breslau-Str., 10 10623 Berlin Germany
| | - Vladimir Kubyshkin
- Institute of Chemistry; Technical University of Berlin; Müller-Breslau-Str., 10 10623 Berlin Germany
| | - Nediljko Budisa
- Institute of Chemistry; Technical University of Berlin; Müller-Breslau-Str., 10 10623 Berlin Germany
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27
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Liao R, Lv P, Wang Q, Zheng J, Feng B, Yang B. Cyclodextrin-based biological stimuli-responsive carriers for smart and precision medicine. Biomater Sci 2018; 5:1736-1745. [PMID: 28726855 DOI: 10.1039/c7bm00443e] [Citation(s) in RCA: 37] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Spurred on by recent progress in nanotechnology and precision medicine, smart drug carriers are entering an entirely new era. Smart drug carriers have been widely studied in recent years as a result of their ability to control drug release under different microenvironments (such as pH, redox, and enzyme) in vivo. Host-guest interactions based on cyclodextrins have proven to be an efficient tool for fabricating smart drug carriers. Because of the application of host-guest interactions, many kinds of biological molecules or supramolecular building blocks can combine into an organic whole at the molecular level. In this review, the features, mechanisms of action, and potent applications of biological stimuli-responsive drug carriers based on cyclodextrins are discussed. In addition, some personal perspectives on this field are presented.
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Affiliation(s)
- Rongqiang Liao
- Department of pharmacy, Chongqing Emergency Medical Center, Chongqing, 400014, P.R. China.
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28
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Sun XZ, Liao Y, Li W, Guo LM. Neuroprotective effects of ganoderma lucidum polysaccharides against oxidative stress-induced neuronal apoptosis. Neural Regen Res 2017; 12:953-958. [PMID: 28761429 PMCID: PMC5514871 DOI: 10.4103/1673-5374.208590] [Citation(s) in RCA: 38] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/21/2023] Open
Abstract
Ganoderma lucidum polysaccharides have protective effects against apoptosis in neurons exposed to ischemia/reperfusion injury, but the mechanisms are unclear. The goal of this study was to investigate the underlying mechanisms of the effects of ganoderma lucidum polysaccharides against oxidative stress-induced neuronal apoptosis. Hydrogen peroxide (H2O2) was used to induce apoptosis in cultured cerebellar granule cells. In these cells, ganoderma lucidum polysaccharides remarkably suppressed H2O2-induced apoptosis, decreased expression of caspase-3, Bax and Bim and increased that of Bcl-2. These findings suggested that ganoderma lucidum polysaccharides regulate expression of apoptosis-associated proteins, inhibit oxidative stress-induced neuronal apoptosis and, therefore, have significant neuroprotective effects.
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Affiliation(s)
- Xin-Zhi Sun
- Department of Orthopedics, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan Province, China
| | - Ying Liao
- Department of Public Security Technology, Railway Police College, Zhengzhou, Henan Province, China.,Department of Pathology, Peking University Health Science Center, Beijing, China
| | - Wei Li
- Department of Public Security Technology, Railway Police College, Zhengzhou, Henan Province, China
| | - Li-Mei Guo
- Department of Pathology, Peking University Health Science Center, Beijing, China
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29
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Abstract
Ischemia as a serious neurodegenerative disorder causes together with reperfusion injury many changes in nervous tissue. Most of the neuronal damage is caused by complex of biochemical reactions and substantial processes, such as protein agregation, reactions of free radicals, insufficient blood supply, glutamate excitotoxicity, and oxidative stress. The result of these processes can be apoptotic or necrotic cell death and it can lead to an irreversible damage. Therefore, neuroprotection and prevention of the neurodegeneration are highly important topics to study. There are several approaches to prevent the ischemic damage. Use of many modern therapeutical methods and the incorporation of several substances into the diet of patients is possible to stimulate the endogenous protective mechanisms and improve the life quality.
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Affiliation(s)
- Maria Lalkovičová
- Institute of Neurobiology, Slovak Academy of Sciences, Kosice, Slovakia
| | - Viera Danielisová
- Institute of Neurobiology, Slovak Academy of Sciences, Kosice, Slovakia
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30
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Lai L, Zhao C, Su M, Li X, Liu X, Jiang H, Amatore C, Wang X. In vivo target bio-imaging of Alzheimer's disease by fluorescent zinc oxide nanoclusters. Biomater Sci 2016; 4:1085-91. [PMID: 27229662 DOI: 10.1039/c6bm00233a] [Citation(s) in RCA: 28] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022]
Abstract
Alzheimer's disease (AD) is an irreversible neurodegenerative disease which is difficult to cure. When Alzheimer's disease occurs, the level of zinc ions in the brain changes, and the relevant amount of zinc ions continue decreasing in the cerebrospinal fluid and plasma of Alzheimer's patients with disease exacerbation. In view of these considerations, we have explored a new strategy for the in vivo rapid fluorescence imaging of Alzheimer's disease through target bio-labeling of zinc oxide nanoclusters which were biosynthesized in vivo in the Alzheimer's brain via intravenous injection of zinc gluconate solution. By using three-month-old and six-month-old Alzheimer's model mice as models, our observations demonstrate that biocompatible zinc ions could pass through the blood-brain barrier of the Alzheimer's disease mice and generate fluorescent zinc oxide nanoclusters (ZnO NCs) through biosynthesis, and then the bio-synthesized ZnO NCs could readily accumulate in situ on the hippocampus specific region for the in vivo fluorescent labeling of the affected sites. This study provides a new way for the rapid diagnosis of Alzheimer's disease and may have promising prospects in the effective diagnosis of Alzheimer's disease.
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Affiliation(s)
- Lanmei Lai
- State Key Laboratory of Bioelectronics, School of Biological Science and Medical Engineering, Southeast University, Nanjing 210096, China.
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