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El-Tanani M, Rabbani SA, Babiker R, El-Tanani Y, Satyam SM, Porntaveetus T. Emerging Multifunctional Biomaterials for Addressing Drug Resistance in Cancer. BIOLOGY 2025; 14:497. [PMID: 40427686 PMCID: PMC12108606 DOI: 10.3390/biology14050497] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 03/25/2025] [Revised: 04/27/2025] [Accepted: 04/29/2025] [Indexed: 05/29/2025]
Abstract
Drug resistance remains a major barrier to effective cancer treatment, contributing to poor patient outcomes. Multifunctional biomaterials integrating electrical and catalytic properties offer a transformative strategy to target diverse resistance mechanisms. This review explores their ability to modulate cellular processes, remodel the tumor microenvironment (TME), and enhance drug delivery. Electrically active biomaterials enhance drug uptake and apoptotic sensitivity by altering membrane potentials, ion channels, and intracellular signaling, synergizing with chemotherapy. Catalytic biomaterials generate reactive oxygen species (ROS), activate prodrugs, reprogram hypoxic and acidic TME, and degrade the extracellular matrix (ECM) to improve drug penetration. Hybrid nanomaterials (e.g., conductive hydrogels, electrocatalytic nanoparticles), synergize electrical and catalytic properties for localized, stimuli-responsive therapy and targeted drug release, minimizing systemic toxicity. Despite challenges in biocompatibility and scalability, future integration with immunotherapy, personalized medicine, and intelligent self-adaptive systems capable of real-time tumor response promises to accelerate clinical translation. The development of these adaptive biomaterials, alongside advancements in nanotechnology and AI-driven platforms, represents the next frontier in precision oncology. This review highlights the potential of multifunctional biomaterials to revolutionize cancer therapy by addressing multidrug resistance at cellular, genetic, and microenvironmental levels, offering a roadmap to improve therapeutic outcomes and reshape oncology practice.
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Affiliation(s)
- Mohamed El-Tanani
- RAK College of Pharmacy, RAK Medical and Health Sciences University, Ras Al Khaimah 11172, United Arab Emirates
| | - Syed Arman Rabbani
- RAK College of Pharmacy, RAK Medical and Health Sciences University, Ras Al Khaimah 11172, United Arab Emirates
| | - Rasha Babiker
- RAK College of Medical Sciences, RAK Medical and Health Sciences University, Ras Al Khaimah 11172, United Arab Emirates
| | | | - Shakta Mani Satyam
- RAK College of Medical Sciences, RAK Medical and Health Sciences University, Ras Al Khaimah 11172, United Arab Emirates
| | - Thantrira Porntaveetus
- Center of Excellence in Precision Medicine and Digital Health, Department of Physiology, Faculty of Dentistry, Chulalongkorn University, Bangkok 10330, Thailand;
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Khan MS, Gowda BHJ, Nasir N, Wahab S, Pichika MR, Sahebkar A, Kesharwani P. Advancements in dextran-based nanocarriers for treatment and imaging of breast cancer. Int J Pharm 2023; 643:123276. [PMID: 37516217 DOI: 10.1016/j.ijpharm.2023.123276] [Citation(s) in RCA: 37] [Impact Index Per Article: 18.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/26/2023] [Revised: 07/12/2023] [Accepted: 07/26/2023] [Indexed: 07/31/2023]
Abstract
Breast cancer is the most prevalent type of cancer worldwide,particularly among women, with substantial side effects after therapy. Despite the availability of numerous therapeutic approaches, particularly chemotherapy, the survival rates for breast cancer have declined over time. The therapies currently utilized for breast cancer treatment do not specifically target cancerous cells, resulting in significant adverse effects and potential harm to healthy cells alongside the cancer cells. As a result, nanoparticle-based drug delivery systems have emerged. Among various types of nanoparticles, natural polysaccharide-based nanoparticles have gained significant attention due to their ability to precisely control the drug release and achieve targeted drug delivery. Moreover, polysaccharides are biocompatible, biodegradable, easily modifiable, and renewable, which makes them a unique material for nanoformulation. In recent years, dextran and its derivatives have gained much interest in the field of breast cancer therapy. Dextran is a hydrophilic polysaccharide composed of a main chain formed by α-1,6 linked glucopyranoside residues and a side chain composed of residues linked in α-1,2/3/4 positions. Different dextran-antitumor medication conjugates enhancethe efficacy of anticancer agents. With this context, the present review provides brief insights into dextran and its modification. Further, it meticulously discusses the role of dextran-based nanoparticles in breast cancer therapy and imaging, followed by snippets on their toxicity. Lastly, it presents clinical trials and future perspectives of dextran-based nanoparticles in breast cancer treatment.
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Affiliation(s)
- Mohammad Sameer Khan
- Department of Pharmaceutics, School of Pharmaceutical Education and Research, Jamia Hamdard, New Delhi 110062, India
| | - B H Jaswanth Gowda
- Department of Pharmaceutics, Yenepoya Pharmacy College & Research Centre, Yenepoya (Deemed to be University), Mangalore 575018, Karnataka, India
| | - Nazim Nasir
- Department of Basic Medical Sciences, College of Applied Medical Sciences, Khamis Mushait, Saudi Arabia
| | - Shadma Wahab
- Department of Pharmacognosy, College of Pharmacy, King Khalid University, Abha 61421, Saudi Arabia
| | - Mallikarjuna Rao Pichika
- Pharmaceutical Chemistry, School of Pharmacy, International Medical University, Kuala Lumpur, Malaysia
| | - Amirhossein Sahebkar
- Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran; Applied Biomedical Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Prashant Kesharwani
- Department of Pharmaceutics, School of Pharmaceutical Education and Research, Jamia Hamdard, New Delhi 110062, India; Department of Pharmacology, Saveetha Dental College, Saveetha Institute of Medical and Technical Sciences, Saveetha University, Chennai, India.
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Aalhate M, Mahajan S, Singh H, Guru SK, Singh PK. Nanomedicine in therapeutic warfront against estrogen receptor-positive breast cancer. Drug Deliv Transl Res 2023; 13:1621-1653. [PMID: 36795198 DOI: 10.1007/s13346-023-01299-7] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 01/06/2023] [Indexed: 02/17/2023]
Abstract
Breast cancer (BC) is the most frequently diagnosed malignancy in women worldwide. Almost 70-80% of cases of BC are curable at the early non-metastatic stage. BC is a heterogeneous disease with different molecular subtypes. Around 70% of breast tumors exhibit estrogen-receptor (ER) expression and endocrine therapy is used for the treatment of these patients. However, there are high chances of recurrence in the endocrine therapy regimen. Though chemotherapy and radiation therapy have substantially improved survival rates and treatment outcomes in BC patients, there is an increased possibility of the development of resistance and dose-limiting toxicities. Conventional treatment approaches often suffer from low bioavailability, adverse effects due to the non-specific action of chemotherapeutics, and low antitumor efficacy. Nanomedicine has emerged as a conspicuous strategy for delivering anticancer therapeutics in BC management. It has revolutionized the area of cancer therapy by increasing the bioavailability of the therapeutics and improving their anticancer efficacy with reduced toxicities on healthy tissues. In this article, we have highlighted various mechanisms and pathways involved in the progression of ER-positive BC. Further, different nanocarriers delivering drugs, genes, and natural therapeutic agents for surmounting BC are the spotlights of this article.
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Affiliation(s)
- Mayur Aalhate
- Department of Pharmaceutics, National Institute of Pharmaceutical Education and Research (NIPER), Hyderabad, Telangana, 500037, India
| | - Srushti Mahajan
- Department of Pharmaceutics, National Institute of Pharmaceutical Education and Research (NIPER), Hyderabad, Telangana, 500037, India
| | - Hoshiyar Singh
- Department of Biological Science, National Institute of Pharmaceutical Education and Research (NIPER), Hyderabad, 500037, India
| | - Santosh Kumar Guru
- Department of Biological Science, National Institute of Pharmaceutical Education and Research (NIPER), Hyderabad, 500037, India
| | - Pankaj Kumar Singh
- Department of Pharmaceutics, National Institute of Pharmaceutical Education and Research (NIPER), Hyderabad, Telangana, 500037, India.
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4
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Lu CH, Hsiao JK. Diagnostic and therapeutic roles of iron oxide nanoparticles in biomedicine. Tzu Chi Med J 2022; 35:11-17. [PMID: 36866343 PMCID: PMC9972926 DOI: 10.4103/tcmj.tcmj_65_22] [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: 03/23/2022] [Revised: 05/03/2022] [Accepted: 06/08/2022] [Indexed: 11/04/2022] Open
Abstract
Nanotechnology changed our understanding of physics and chemics and influenced the biomedical field. Iron oxide nanoparticles (IONs) are one of the first emerging biomedical applications of nanotechnology. The IONs are composed of iron oxide core exhibiting magnetism and coated with biocompatible molecules. The small size, strong magnetism, and biocompatibility of IONs facilitate the application of IONs in the medical imaging field. We listed several clinical available IONs including Resovist (Bayer Schering Pharma, Berlin, Germany) and Feridex intravenous (I.V.)/Endorem as magnetic resonance (MR) contrast agents for liver tumor detection. We also illustrated GastroMARK as a gastrointestinal contrast agent for MR imaging. Recently, IONs named Feraheme for treating iron-deficiency anemia have been approved by the Food and Drug Administration. Moreover, tumor ablation by IONs named NanoTherm has also been discussed. In addition to the clinical application, several potential biomedical applications of IONs including cancer-targeting capability by conjugating IONs with cancer-specific ligands, cell trafficking tools, or tumor ablation agents have also been discussed. With the growing awareness of nanotechnology, further application of IONs is still on the horizon that would shed light on biomedicine.
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Affiliation(s)
- Chia-Hung Lu
- Department of Medical Imaging, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, New Taipei, Taiwan
| | - Jong-Kai Hsiao
- Department of Medical Imaging, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, New Taipei, Taiwan,School of Medicine, Tzu Chi University, Hualien, Taiwan,Address for correspondence: Dr. Jong-Kia Hsiao, Department of Medical Imaging, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, 289, Jianguo Road, Xindian District, New Taipei, Taiwan. E-mail:
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Nanomaterial-Based Drug Delivery System Targeting Lymph Nodes. Pharmaceutics 2022; 14:pharmaceutics14071372. [PMID: 35890268 PMCID: PMC9325242 DOI: 10.3390/pharmaceutics14071372] [Citation(s) in RCA: 18] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/21/2022] [Revised: 05/28/2022] [Accepted: 06/22/2022] [Indexed: 02/06/2023] Open
Abstract
The lymphatic system plays an indispensable role in humoral balance, lipid metabolism, and immune regulation. The lymph nodes (LNs) are known as the primary sites of tumor metastasis and the metastatic LNs largely affected the prognosis of the patiens. A well-designed lymphatic-targeted system favors disease treatment as well as vaccination efficacy. In recent years, development of nanotechnologies and emerging biomaterials have gained increasing attention in developing lymph-node-targeted drug-delivery systems. By mimicking the endogenous macromolecules or lipid conjugates, lymph-node-targeted nanocarries hold potential for disease diagnosis and tumor therapy. This review gives an introduction to the physiological functions of LNs and the roles of LNs in diseases, followed by a review of typical lymph-node-targeted nanomaterial-based drug-delivery systems (e.g., liposomes, micelles, inorganic nanomaterials, hydrogel, and nanocapsules). Future perspectives and conclusions concerned with lymph-node-targeted drug-delivery systems are also provided.
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Sitia L, Sevieri M, Signati L, Bonizzi A, Chesi A, Mainini F, Corsi F, Mazzucchelli S. HER-2-Targeted Nanoparticles for Breast Cancer Diagnosis and Treatment. Cancers (Basel) 2022; 14:2424. [PMID: 35626028 PMCID: PMC9139811 DOI: 10.3390/cancers14102424] [Citation(s) in RCA: 30] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/13/2022] [Revised: 05/09/2022] [Accepted: 05/10/2022] [Indexed: 02/01/2023] Open
Abstract
Human epidermal growth factor receptor-2 (HER-2) overexpressing breast cancer is a breast cancer subtype characterized by high aggressiveness, high frequency of brain metastases and poor prognosis. HER-2, a glycoprotein belonging to the ErbB receptor family, is overexpressed on the outer membrane of cancer cells and has been an important therapeutic target for the development of targeted drugs, such as the monoclonal antibodies trastuzumab and pertuzumab. These therapies have been available in clinics for more than twenty years. However, despite the initial enthusiasm, a major issue emerged limiting HER-2 targeted therapy efficacy, i.e., the evolution of drug resistance, which could be tackled by nanotechnology. The aim of this review is to provide a first critical update on the different types of HER-2-targeted nanoparticles that have been proposed in the literature in the last decade for therapeutic purposes. We focus on the different targeting strategies that have been explored, their relative outcomes and current limitations that still need to be improved. Then, we review the nanotools developed as diagnostic kits, focusing on the most recent techniques, which allow accurate quantification of HER-2 levels in tissues, with the aim of promoting more personalized medicinal approaches in patients.
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Affiliation(s)
- Leopoldo Sitia
- Dipartimento di Scienze Biomediche e Cliniche, Università di Milano, 20157 Milano, Italy; (L.S.); (M.S.); (L.S.); (A.B.); (A.C.); (F.M.); (F.C.)
| | - Marta Sevieri
- Dipartimento di Scienze Biomediche e Cliniche, Università di Milano, 20157 Milano, Italy; (L.S.); (M.S.); (L.S.); (A.B.); (A.C.); (F.M.); (F.C.)
| | - Lorena Signati
- Dipartimento di Scienze Biomediche e Cliniche, Università di Milano, 20157 Milano, Italy; (L.S.); (M.S.); (L.S.); (A.B.); (A.C.); (F.M.); (F.C.)
| | - Arianna Bonizzi
- Dipartimento di Scienze Biomediche e Cliniche, Università di Milano, 20157 Milano, Italy; (L.S.); (M.S.); (L.S.); (A.B.); (A.C.); (F.M.); (F.C.)
| | - Arianna Chesi
- Dipartimento di Scienze Biomediche e Cliniche, Università di Milano, 20157 Milano, Italy; (L.S.); (M.S.); (L.S.); (A.B.); (A.C.); (F.M.); (F.C.)
| | - Francesco Mainini
- Dipartimento di Scienze Biomediche e Cliniche, Università di Milano, 20157 Milano, Italy; (L.S.); (M.S.); (L.S.); (A.B.); (A.C.); (F.M.); (F.C.)
| | - Fabio Corsi
- Dipartimento di Scienze Biomediche e Cliniche, Università di Milano, 20157 Milano, Italy; (L.S.); (M.S.); (L.S.); (A.B.); (A.C.); (F.M.); (F.C.)
- IRCCS Istituti Clinici Scientifici Salvatore Maugeri, 27100 Pavia, Italy
| | - Serena Mazzucchelli
- Dipartimento di Scienze Biomediche e Cliniche, Università di Milano, 20157 Milano, Italy; (L.S.); (M.S.); (L.S.); (A.B.); (A.C.); (F.M.); (F.C.)
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Hafez AA, Salimi A, Jamali Z, Shabani M, Sheikhghaderi H. Overview of the application of inorganic nanomaterials in breast cancer diagnosis. INORG NANO-MET CHEM 2022. [DOI: 10.1080/24701556.2021.2025085] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/18/2022]
Affiliation(s)
- Asghar Ashrafi Hafez
- Cancer Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Ahmad Salimi
- Department of Pharmacology and Toxicology, School of Pharmacy, Ardabil University of Medical Sciences, Ardabil, Iran
- Traditional Medicine and Hydrotherapy Research Center, Ardabil University of Medical Sciences, Ardabil, Iran
| | - Zhaleh Jamali
- Student Research Committee, School of Medicine, Shahroud University of Medical Sciences, Shahroud, Iran
| | - Mohammad Shabani
- Student Research Committee, School of Pharmacy, Ardabil University of Medical Sciences, Ardabil, Iran
| | - Hiva Sheikhghaderi
- Student Research Committee, School of Paramedical, Kermanshah University of Medical Sciences, Kermanshah, Iran
- Bukan Shahid Gholipour Hospital, Urmia University of Medical Sciences, Bukan, Iran
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8
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Fakhardo A, Anastasova E, Makarov V, Ikonnikova EV, Kulko E, Nicole A, Yakunina M, Shkodenko L, Tsvetikova SA, Toropko M, Koshel EI, Zakharov M, Alexandrov G, Khuttunen O, Kulikov P, Burmistrov O, Vinogradov VV, Prilepskii AY. Heparin-coated iron oxide nanoparticles: application as liver contrast agent, toxicity and pharmacokinetics. J Mater Chem B 2022; 10:7797-7807. [DOI: 10.1039/d2tb00759b] [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
The newly prepared heparin-coated iron oxide nanoparticles (Hep-IONPs) contrasted cholangioma tumors in the liver in T2 MRI. NPs were not toxic to rats and rabbits after 14 days of consecutive...
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9
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Mason EE, Mattingly E, Herb K, Śliwiak M, Franconi S, Cooley CZ, Slanetz PJ, Wald LL. Concept for using magnetic particle imaging for intraoperative margin analysis in breast-conserving surgery. Sci Rep 2021; 11:13456. [PMID: 34188077 PMCID: PMC8242088 DOI: 10.1038/s41598-021-92644-8] [Citation(s) in RCA: 19] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/02/2021] [Accepted: 06/11/2021] [Indexed: 12/23/2022] Open
Abstract
Breast-conserving surgery (BCS) is a commonly utilized treatment for early stage breast cancers but has relatively high reexcision rates due to post-surgical identification of positive margins. A fast, specific, sensitive, easy-to-use tool for assessing margins intraoperatively could reduce the need for additional surgeries, and while many techniques have been explored, the clinical need is still unmet. We assess the potential of Magnetic Particle Imaging (MPI) for intraoperative margin assessment in BCS, using a passively or actively tumor-targeted iron oxide agent and two hardware devices: a hand-held Magnetic Particle detector for identifying residual tumor in the breast, and a small-bore MPI scanner for quickly imaging the tumor distribution in the excised specimen. Here, we present both hardware systems and demonstrate proof-of-concept detection and imaging of clinically relevant phantoms.
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Affiliation(s)
- Erica E Mason
- Department of Radiology, A. A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Charlestown, MA, 02129, USA.
- Harvard-MIT Division of Health Sciences and Technology, Cambridge, MA, 02139, USA.
| | - Eli Mattingly
- Harvard-MIT Division of Health Sciences and Technology, Cambridge, MA, 02139, USA
| | - Konstantin Herb
- Department of Radiology, A. A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Charlestown, MA, 02129, USA
- Department of Physics, ETH Zurich, Zurich, Switzerland
| | - Monika Śliwiak
- Department of Radiology, A. A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Charlestown, MA, 02129, USA
| | - Sofia Franconi
- Department of Radiology, A. A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Charlestown, MA, 02129, USA
| | - Clarissa Zimmerman Cooley
- Department of Radiology, A. A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Charlestown, MA, 02129, USA
- Harvard Medical School, Boston, MA, 02115, USA
| | - Priscilla J Slanetz
- Department of Radiology, Boston University Medical Center, Boston, MA, 02118, USA
| | - Lawrence L Wald
- Department of Radiology, A. A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Charlestown, MA, 02129, USA
- Harvard Medical School, Boston, MA, 02115, USA
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10
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Multifunctional nanoparticles as optical biosensing probe for breast cancer detection: A review. MATERIALS SCIENCE & ENGINEERING. C, MATERIALS FOR BIOLOGICAL APPLICATIONS 2021; 127:112249. [PMID: 34225888 DOI: 10.1016/j.msec.2021.112249] [Citation(s) in RCA: 22] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/05/2020] [Revised: 05/11/2021] [Accepted: 06/05/2021] [Indexed: 12/15/2022]
Abstract
Optical biosensors show attractive performance in medical sensing in the event of using different nanoparticles in their design. Owing to their unique optical characteristics and biological compatibility, gold nanoparticles (GNPs), silver nanoparticles (AgNPs), bimetallic nanoparticles and magnetic nanoparticles have been broadly implemented in making sensing tools. The functionalization of these nanoparticles with different components provides an excellent opportunity to assemble selective and sensitive sensing materials to detect various biological molecules related to breast cancer. This review summarizes the recent application of optical biosensing devices based on nanomaterials and discusses their pros and cons to improve breast cancer detection in real samples. In particular, the main constituent elements of these optical biosensors including recognition and transducer elements, types of applied nanostructures, analytical sensing procedures, sensor detection ranges and limit of detection (LOD), are expressed in detail.
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11
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Crețu BEB, Dodi G, Shavandi A, Gardikiotis I, Șerban IL, Balan V. Imaging Constructs: The Rise of Iron Oxide Nanoparticles. Molecules 2021; 26:3437. [PMID: 34198906 PMCID: PMC8201099 DOI: 10.3390/molecules26113437] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/24/2021] [Revised: 05/27/2021] [Accepted: 06/01/2021] [Indexed: 12/14/2022] Open
Abstract
Over the last decade, an important challenge in nanomedicine imaging has been the work to design multifunctional agents that can be detected by single and/or multimodal techniques. Among the broad spectrum of nanoscale materials being investigated for imaging use, iron oxide nanoparticles have gained significant attention due to their intrinsic magnetic properties, low toxicity, large magnetic moments, superparamagnetic behaviour and large surface area-the latter being a particular advantage in its conjunction with specific moieties, dye molecules, and imaging probes. Tracers-based nanoparticles are promising candidates, since they combine synergistic advantages for non-invasive, highly sensitive, high-resolution, and quantitative imaging on different modalities. This study represents an overview of current advancements in magnetic materials with clinical potential that will hopefully provide an effective system for diagnosis in the near future. Further exploration is still needed to reveal their potential as promising candidates from simple functionalization of metal oxide nanomaterials up to medical imaging.
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Affiliation(s)
- Bianca Elena-Beatrice Crețu
- Advanced Centre for Research-Development in Experimental Medicine, Grigore T. Popa University of Medicine and Pharmacy of Iasi, 700115 Iasi, Romania; (B.E.-B.C.); (I.G.)
| | - Gianina Dodi
- Advanced Centre for Research-Development in Experimental Medicine, Grigore T. Popa University of Medicine and Pharmacy of Iasi, 700115 Iasi, Romania; (B.E.-B.C.); (I.G.)
| | - Amin Shavandi
- BioMatter-Biomass Transformation Lab, École Polytechnique de Bruxelles, Université Libre de Bruxelles, 1050 Brussels, Belgium;
| | - Ioannis Gardikiotis
- Advanced Centre for Research-Development in Experimental Medicine, Grigore T. Popa University of Medicine and Pharmacy of Iasi, 700115 Iasi, Romania; (B.E.-B.C.); (I.G.)
| | - Ionela Lăcrămioara Șerban
- Physiology Department, Grigore T. Popa University of Medicine and Pharmacy of Iasi, 700115 Iasi, Romania;
| | - Vera Balan
- Faculty of Medical Bioengineering, Grigore T. Popa University of Medicine and Pharmacy of Iasi, 700115 Iasi, Romania;
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12
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Serkova NJ, Glunde K, Haney CR, Farhoud M, De Lille A, Redente EF, Simberg D, Westerly DC, Griffin L, Mason RP. Preclinical Applications of Multi-Platform Imaging in Animal Models of Cancer. Cancer Res 2021; 81:1189-1200. [PMID: 33262127 PMCID: PMC8026542 DOI: 10.1158/0008-5472.can-20-0373] [Citation(s) in RCA: 35] [Impact Index Per Article: 8.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/04/2020] [Revised: 06/10/2020] [Accepted: 11/25/2020] [Indexed: 11/16/2022]
Abstract
In animal models of cancer, oncologic imaging has evolved from a simple assessment of tumor location and size to sophisticated multimodality exploration of molecular, physiologic, genetic, immunologic, and biochemical events at microscopic to macroscopic levels, performed noninvasively and sometimes in real time. Here, we briefly review animal imaging technology and molecular imaging probes together with selected applications from recent literature. Fast and sensitive optical imaging is primarily used to track luciferase-expressing tumor cells, image molecular targets with fluorescence probes, and to report on metabolic and physiologic phenotypes using smart switchable luminescent probes. MicroPET/single-photon emission CT have proven to be two of the most translational modalities for molecular and metabolic imaging of cancers: immuno-PET is a promising and rapidly evolving area of imaging research. Sophisticated MRI techniques provide high-resolution images of small metastases, tumor inflammation, perfusion, oxygenation, and acidity. Disseminated tumors to the bone and lung are easily detected by microCT, while ultrasound provides real-time visualization of tumor vasculature and perfusion. Recently available photoacoustic imaging provides real-time evaluation of vascular patency, oxygenation, and nanoparticle distributions. New hybrid instruments, such as PET-MRI, promise more convenient combination of the capabilities of each modality, enabling enhanced research efficacy and throughput.
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Affiliation(s)
- Natalie J Serkova
- Department of Radiology, University of Colorado Anschutz Medical Campus, Aurora, Colorado.
- Animal Imaging Shared Resource, University of Colorado Cancer Center, Aurora, Colorado
| | - Kristine Glunde
- Division of Cancer Imaging Research, The Russell H. Morgan Department of Radiology, and the Sydney Kimmel Comprehensive Cancer Center, Johns Hopkins Medical Institutions, Baltimore, Maryland
| | - Chad R Haney
- Center for Advanced Molecular Imaging, Northwestern University, Evanston, Illinois
| | | | | | | | - Dmitri Simberg
- Department of Pharmaceutical Sciences, University of Colorado Anschutz Medical Campus, Aurora, Colorado
| | - David C Westerly
- Animal Imaging Shared Resource, University of Colorado Cancer Center, Aurora, Colorado
- Department of Radiation Oncology, University of Colorado Anschutz Medical Campus, Aurora, Colorado
| | - Lynn Griffin
- Department of Radiology, Veterinary Teaching Hospital, Colorado State University, Fort Collins, Colorado
| | - Ralph P Mason
- Department of Radiology, University of Texas Southwestern, Dallas, Texas
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13
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Molecular Targeting of Epidermal Growth Factor Receptor (EGFR) and Vascular Endothelial Growth Factor Receptor (VEGFR). Molecules 2021; 26:molecules26041076. [PMID: 33670650 PMCID: PMC7922143 DOI: 10.3390/molecules26041076] [Citation(s) in RCA: 56] [Impact Index Per Article: 14.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/31/2021] [Revised: 02/13/2021] [Accepted: 02/16/2021] [Indexed: 12/13/2022] Open
Abstract
Epidermal growth factor receptor (EGFR) and vascular endothelial growth factor receptor (VEGFR) are two extensively studied membrane-bound receptor tyrosine kinase proteins that are frequently overexpressed in many cancers. As a result, these receptor families constitute attractive targets for imaging and therapeutic applications in the detection and treatment of cancer. This review explores the dynamic structure and structure-function relationships of these two growth factor receptors and their significance as it relates to theranostics of cancer, followed by some of the common inhibition modalities frequently employed to target EGFR and VEGFR, such as tyrosine kinase inhibitors (TKIs), antibodies, nanobodies, and peptides. A summary of the recent advances in molecular imaging techniques, including positron emission tomography (PET), single-photon emission computerized tomography (SPECT), computed tomography (CT), magnetic resonance imaging (MRI), and optical imaging (OI), and in particular, near-IR fluorescence imaging using tetrapyrrolic-based fluorophores, concludes this review.
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Popescu Din IM, Balas M, Hermenean A, Vander Elst L, Laurent S, Burtea C, Cinteza LO, Dinischiotu A. Novel Polymeric Micelles-Coated Magnetic Nanoparticles for In Vivo Bioimaging of Liver: Toxicological Profile and Contrast Enhancement. MATERIALS (BASEL, SWITZERLAND) 2020; 13:E2722. [PMID: 32549296 PMCID: PMC7345181 DOI: 10.3390/ma13122722] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 05/25/2020] [Revised: 06/10/2020] [Accepted: 06/11/2020] [Indexed: 12/11/2022]
Abstract
Magnetic nanoparticles are intensively studied for magnetic resonance imaging (MRI) as contrast agents but yet there remained some gaps regarding their toxicity potential and clinical implications of their biodistribution in organs. This study presents the effects induced by magnetite nanoparticles encapsulated in polymeric micelles (MNP-DSPE-PEG) on biochemical markers, metabolic functions, and MRI signal in CD1 mice liver. Three groups of animals, one control and the other ones injected with a suspension of five, respectively, 15 mg Fe/kg bw nanoparticles, were monitored up to 14 days. The results indicated the presence of MNP-DSPE-PEG in the liver in the first two days of the experiment. The most significant biochemical changes also occurred in the first 3 days after exposure when the most severe histological changes were observed. The change of the MRI signal intensity on the T2-weighted images and increased transverse relaxation rates R2 in the liver were observed after the first minutes from the nanoparticle administration. The study shows that the alterations of biomarkers level resulting from exposure to MNP-DSPE-PEG are restored in time in mice liver. This was associated with a significant contrast on T2-weighted images and made us conclude that these nanoparticles might be potential candidates for use as a contrast agent in liver medical imaging.
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Affiliation(s)
- Ioana Mihaela Popescu Din
- Department of Biochemistry and Molecular Biology, Faculty of Biology, University of Bucharest, 91–95 Splaiul Independentei, 050095 Bucharest, Romania; (I.M.P.D.); (A.D.)
| | - Mihaela Balas
- Department of Biochemistry and Molecular Biology, Faculty of Biology, University of Bucharest, 91–95 Splaiul Independentei, 050095 Bucharest, Romania; (I.M.P.D.); (A.D.)
| | - Anca Hermenean
- Department of Experimental and Applied Biology, Institute of Life Sciences, Vasile Goldis Western University of Arad, 86 Rebreanu, 310414 Arad, Romania;
- Department of Histology, Faculty of Medicine, Vasile Goldis Western University of Arad, 1 Feleacului street, 310396 Arad, Romania
| | - Luce Vander Elst
- Department of General, Organic and Biomedical Chemistry, NMR and Molecular Imaging Laboratory, Faculty of Medicine and Pharmacy, University of Mons, 19, Avenue Maistriau, Mendeleev Building, B-7000 Mons, Belgium; (L.V.E.); (S.L.); (C.B.)
| | - Sophie Laurent
- Department of General, Organic and Biomedical Chemistry, NMR and Molecular Imaging Laboratory, Faculty of Medicine and Pharmacy, University of Mons, 19, Avenue Maistriau, Mendeleev Building, B-7000 Mons, Belgium; (L.V.E.); (S.L.); (C.B.)
| | - Carmen Burtea
- Department of General, Organic and Biomedical Chemistry, NMR and Molecular Imaging Laboratory, Faculty of Medicine and Pharmacy, University of Mons, 19, Avenue Maistriau, Mendeleev Building, B-7000 Mons, Belgium; (L.V.E.); (S.L.); (C.B.)
| | - Ludmila Otilia Cinteza
- Department of Physical Chemistry, Faculty of Chemistry, University of Bucharest, 4-12 Regina Elisabeta Blvd, 030018 Bucharest, Romania;
| | - Anca Dinischiotu
- Department of Biochemistry and Molecular Biology, Faculty of Biology, University of Bucharest, 91–95 Splaiul Independentei, 050095 Bucharest, Romania; (I.M.P.D.); (A.D.)
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15
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Targeting strategies for superparamagnetic iron oxide nanoparticles in cancer therapy. Acta Biomater 2020; 102:13-34. [PMID: 31759124 DOI: 10.1016/j.actbio.2019.11.027] [Citation(s) in RCA: 137] [Impact Index Per Article: 27.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/08/2019] [Revised: 11/01/2019] [Accepted: 11/12/2019] [Indexed: 12/12/2022]
Abstract
Among various nanoparticles, superparamagnetic iron oxide nanoparticles (SPIONs) have been increasingly studied for their excellent superparamagnetism, magnetic heating properties, and enhanced magnetic resonance imaging (MRI). The conjugation of SPIONs with drugs to obtain delivery nanosystems has several advantages including magnetic targeted functionalization, in vivo imaging, magnetic thermotherapy, and combined delivery of anticancer agents. To further increase the targeting efficiency of drugs through a delivery nanosystem based on SPIONs, additional targeting moieties including transferrin, antibodies, aptamers, hyaluronic acid, folate, and targeting peptides are coated onto the surface of SPIONs. Therefore, this review summarizes the latest progresses in the conjugation of targeting molecules and drug delivery nanosystems based on SPIONs, especially focusing on their performances to develop efficient targeted drug delivery systems for tumor therapy. STATEMENT OF SIGNIFICANCE: Some magnetic nanoparticle-based nanocarriers loaded with drugs were evaluated in patients and did not produce convincing results, leading to termination of clinical development in phase II/III. An alternative strategy for drug delivery systems based on SPIONs is the conjugation of these systems with targeting segments such as transferrin, antibodies, aptamers, hyaluronic acid, folate, and targeting peptides. These targeting moieties can be recognized by specific integrin/receptors that are overexpressed specifically on the tumor cell surface, resulting in minimizing dosage and reducing off-target effects. This review focuses on magnetic nanoparticle-based nonviral drug delivery systems with targeting moieties to deliver anticancer drugs, with an aim to provide suggestions on the development of SPIONs through discussion.
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Palanisamy S, Wang YM. Superparamagnetic iron oxide nanoparticulate system: synthesis, targeting, drug delivery and therapy in cancer. Dalton Trans 2019; 48:9490-9515. [PMID: 31211303 DOI: 10.1039/c9dt00459a] [Citation(s) in RCA: 122] [Impact Index Per Article: 20.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
Cancer is a global epidemic and is considered a leading cause of death. Various cancer treatments such as chemotherapy, surgery, and radiotherapy are available for the cure but those are generally associated with poor long-term survival rates. Consequently, more advanced and selective methods that have better outcomes, fewer side effects, and high efficacies are highly in demand. Among these is the use of superparamagnetic iron oxide nanoparticles (SPIONs) which act as an innovative kit for battling cancer. Low cost, magnetic properties and toxicity properties enable SPIONs to be widely utilized in biomedical applications. For example, magnetite and maghemite (Fe3O4 and γ-Fe2O3) exhibit superparamagnetic properties and are widely used in drug delivery, diagnosis, and therapy. These materials are termed SPIONs when their size is smaller than 20 nm. This review article aims to provide a brief introduction on SPIONs, focusing on their fundamental magnetism and biological applications. The quality and surface chemistry of SPIONs are crucial in biomedical applications; therefore an in-depth survey of synthetic approaches and surface modifications of SPIONs is provided along with their biological applications such as targeting, site-specific drug delivery and therapy.
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Affiliation(s)
- Sathyadevi Palanisamy
- Department of Biological Science and Technology, Institute of Molecular Medicine and Bioengineering, National Chiao Tung University, 75 Bo-Ai Street, Hsinchu 300, Taiwan.
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Sivasubramanian M, Chuang YC, Chen NT, Lo LW. Seeing Better and Going Deeper in Cancer Nanotheranostics. Int J Mol Sci 2019; 20:E3490. [PMID: 31315232 PMCID: PMC6678689 DOI: 10.3390/ijms20143490] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/15/2019] [Revised: 07/12/2019] [Accepted: 07/12/2019] [Indexed: 02/07/2023] Open
Abstract
Biomedical imaging modalities in clinical practice have revolutionized oncology for several decades. State-of-the-art biomedical techniques allow visualizing both normal physiological and pathological architectures of the human body. The use of nanoparticles (NP) as contrast agents enabled visualization of refined contrast images with superior resolution, which assists clinicians in more accurate diagnoses and in planning appropriate therapy. These desirable features are due to the ability of NPs to carry high payloads (contrast agents or drugs), increased in vivo half-life, and disease-specific accumulation. We review the various NP-based interventions for treatments of deep-seated tumors, involving "seeing better" to precisely visualize early diagnosis and "going deeper" to activate selective therapeutics in situ.
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Affiliation(s)
- Maharajan Sivasubramanian
- Institute of Biomedical Engineering and Nanomedicine, National Health Research Institutes, Zhunan 350, Taiwan
| | - Yao Chen Chuang
- Institute of Biomedical Engineering and Nanomedicine, National Health Research Institutes, Zhunan 350, Taiwan
| | - Nai-Tzu Chen
- Department of Cosmeceutics, China Medical University, Taichung 40402, Taiwan.
- Department of Biological Science and Technology, China Medical University, Taichung 40402, Taiwan.
| | - Leu-Wei Lo
- Institute of Biomedical Engineering and Nanomedicine, National Health Research Institutes, Zhunan 350, Taiwan.
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Rajitha B, Malla RR, Vadde R, Kasa P, Prasad GLV, Farran B, Kumari S, Pavitra E, Kamal MA, Raju GSR, Peela S, Nagaraju GP. Horizons of nanotechnology applications in female specific cancers. Semin Cancer Biol 2019; 69:376-390. [PMID: 31301361 DOI: 10.1016/j.semcancer.2019.07.005] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/03/2019] [Revised: 06/23/2019] [Accepted: 07/04/2019] [Indexed: 12/20/2022]
Abstract
Female-specific cancers are the most common cancers in women worldwide. Early detection methods remain unavailable for most of these cancers, signifying that most of them are diagnosed at later stages. Furthermore, current treatment options for most female-specific cancers are surgery, radiation and chemotherapy. Although important milestones in molecularly targeted approaches have been achieved lately, current therapeutic strategies for female-specific cancers remain limited, ineffective and plagued by the emergence of chemoresistance, which aggravates prognosis. Recently, the application of nanotechnology to the medical field has allowed the development of novel nano-based approaches for the management and treatment of cancers, including female-specific cancers. These approaches promise to improve patient survival rates by reducing side effects, enabling selective delivery of drugs to tumor tissues and enhancing the uptake of therapeutic compounds, thus increasing anti-tumor activity. In this review, we focus on the application of nano-based technologies to the design of novel and innovative diagnostic and therapeutic strategies in the context of female-specific cancers, highlighting their potential uses and limitations.
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Affiliation(s)
- Balney Rajitha
- Department of Pathology, WellStar Hospital, Marietta, GA, 30060, USA
| | - Rama Rao Malla
- Department of Biochemistry, GITAM Institute of Science, GITAM University, Visakhapatnam, AP, 530045, India
| | - Ramakrishna Vadde
- Department of Biotechnology and Bioinformatics, Yogi Vemana University, Kadapa, AP, 516003, India
| | - Prameswari Kasa
- Dr. LV Prasad Diagnostics and Research Laboratory, Khairtabad, Hyderabad, TS, 500004, India
| | | | - Batoul Farran
- Department of Hematology and Medical Oncology, Winship Cancer Institute, Emory University, Atlanta, GA, 30322, USA
| | - Seema Kumari
- Department of Biochemistry, GITAM Institute of Science, GITAM University, Visakhapatnam, AP, 530045, India
| | - Eluri Pavitra
- Department of Biological Engineering, Biohybrid Systems Research Center (BSRC), Inha University, 100, Inha-ro, Incheon 22212, Republic of Korea
| | - Mohammad Amjad Kamal
- King Fahd Medical Research Center, King Abdulaziz University, P. O. Box 80216, Jeddah 21589, Saudi Arabia; Enzymoics, 7 Peterlee Place, Hebersham, NSW 2770, Australia; Novel Global Community Educational Foundation, Australia
| | - Ganji Seeta Rama Raju
- Department of Energy and Materials Engineering, Dongguk University-Seoul, Seoul 04620, Republic of Korea
| | - Sujatha Peela
- Department of Biotechnology, Dr. B.R. Ambedkar University, Srikakulam, AP, 532410, India
| | - Ganji Purnachandra Nagaraju
- Department of Hematology and Medical Oncology, Winship Cancer Institute, Emory University, Atlanta, GA, 30322, USA.
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Kaliamurthi S, Demir-Korkmaz A, Selvaraj G, Gokce-Polat E, Wei YK, Almessiere MA, Baykal A, Gu K, Wei DQ. Viewing the Emphasis on State-of-the-Art Magnetic Nanoparticles: Synthesis, Physical Properties, and Applications in Cancer Theranostics. Curr Pharm Des 2019; 25:1505-1523. [PMID: 31119998 DOI: 10.2174/1381612825666190523105004] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/09/2019] [Accepted: 05/16/2019] [Indexed: 02/07/2023]
Abstract
Cancer-related mortality is a leading cause of death among both men and women around the world. Target-specific therapeutic drugs, early diagnosis, and treatment are crucial to reducing the mortality rate. One of the recent trends in modern medicine is "Theranostics," a combination of therapeutics and diagnosis. Extensive interest in magnetic nanoparticles (MNPs) and ultrasmall superparamagnetic iron oxide nanoparticles (NPs) has been increasing due to their biocompatibility, superparamagnetism, less-toxicity, enhanced programmed cell death, and auto-phagocytosis on cancer cells. MNPs act as a multifunctional, noninvasive, ligand conjugated nano-imaging vehicle in targeted drug delivery and diagnosis. In this review, we primarily discuss the significance of the crystal structure, magnetic properties, and the most common method for synthesis of the smaller sized MNPs and their limitations. Next, the recent applications of MNPs in cancer therapy and theranostics are discussed, with certain preclinical and clinical experiments. The focus is on implementation and understanding of the mechanism of action of MNPs in cancer therapy through passive and active targeting drug delivery (magnetic drug targeting and targeting ligand conjugated MNPs). In addition, the theranostic application of MNPs with a dual and multimodal imaging system for early diagnosis and treatment of various cancer types including breast, cervical, glioblastoma, and lung cancer is reviewed. In the near future, the theranostic potential of MNPs with multimodality imaging techniques may enhance the acuity of personalized medicine in the diagnosis and treatment of individual patients.
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Affiliation(s)
- Satyavani Kaliamurthi
- Center of Interdisciplinary Sciences-Computational Life Sciences, College of Food Science and Engineering, Henan University of Technology, Zhengzhou High-tech Industrial Development Zone, 100 Lianhua Street, Zhengzhou, Henan 450001, China
- College of Chemistry, Chemical and Environmental Engineering, Henan University of Technology, Zhengzhou Hightech Industrial Development Zone, 100 Lianhua Street, Zhengzhou, Henan 450001, China
| | - Ayse Demir-Korkmaz
- Department of Chemistry, Istanbul Medeniyet University, 34700 Uskudar, Istanbul, Turkey
| | - Gurudeeban Selvaraj
- Center of Interdisciplinary Sciences-Computational Life Sciences, College of Food Science and Engineering, Henan University of Technology, Zhengzhou High-tech Industrial Development Zone, 100 Lianhua Street, Zhengzhou, Henan 450001, China
- College of Chemistry, Chemical and Environmental Engineering, Henan University of Technology, Zhengzhou Hightech Industrial Development Zone, 100 Lianhua Street, Zhengzhou, Henan 450001, China
| | - Emine Gokce-Polat
- Department of Engineering Physics, Istanbul Medeniyet University, 34700 Uskudar, Istanbul, Turkey
| | - Yong-Kai Wei
- College of Science, Henan University of Technology, Zhengzhou High-tech Industrial Development Zone, 100 Lianhua Street, Zhengzhou, Henan 450001, China
| | - Munirah A Almessiere
- Department of Physics, College of Science, Imam Abdulrahman Bin Faisal University, P.O. Box 1982, 31441 Dammam, Saudi Arabia
| | - Abdulhadi Baykal
- Department of Nano-Medicine Research, Institute for Research & Medical Consultations (IRMC), Imam Abdulrahman Bin Faisal University, P.O. Box 1982, 31441 Dammam, Saudi Arabia
| | - Keren Gu
- Center of Interdisciplinary Sciences-Computational Life Sciences, College of Food Science and Engineering, Henan University of Technology, Zhengzhou High-tech Industrial Development Zone, 100 Lianhua Street, Zhengzhou, Henan 450001, China
- College of Chemistry, Chemical and Environmental Engineering, Henan University of Technology, Zhengzhou Hightech Industrial Development Zone, 100 Lianhua Street, Zhengzhou, Henan 450001, China
| | - Dong-Qing Wei
- Center of Interdisciplinary Sciences-Computational Life Sciences, College of Food Science and Engineering, Henan University of Technology, Zhengzhou High-tech Industrial Development Zone, 100 Lianhua Street, Zhengzhou, Henan 450001, China
- The State Key Laboratory of Microbial Metabolism, College of Life Sciences and Biotechnology, Shanghai Jiao Tong University, No: 800 Dongchuan Road, Minhang, Shanghai, 200240, China
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20
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Raghava Reddy K, Reddy PA, Reddy CV, Shetti NP, Babu B, Ravindranadh K, Shankar MV, Reddy MC, Soni S, Naveen S. Functionalized magnetic nanoparticles/biopolymer hybrids: Synthesis methods, properties and biomedical applications. METHODS IN MICROBIOLOGY 2019. [DOI: 10.1016/bs.mim.2019.04.005] [Citation(s) in RCA: 26] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
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21
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Ullah S, Seidel K, Türkkan S, Warwas DP, Dubich T, Rohde M, Hauser H, Behrens P, Kirschning A, Köster M, Wirth D. Macrophage entrapped silica coated superparamagnetic iron oxide particles for controlled drug release in a 3D cancer model. J Control Release 2018; 294:327-336. [PMID: 30586597 DOI: 10.1016/j.jconrel.2018.12.040] [Citation(s) in RCA: 32] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/15/2018] [Revised: 12/06/2018] [Accepted: 12/21/2018] [Indexed: 12/19/2022]
Abstract
Targeted delivery of drugs is a major challenge in treatment of diverse diseases. Systemically administered drugs demand high doses and are accompanied by poor selectivity and side effects on non-target cells. Here, we introduce a new principle for targeted drug delivery. It is based on macrophages as transporters for nanoparticle-coupled drugs as well as controlled release of drugs by hyperthermia mediated disruption of the cargo cells and simultaneous deliberation of nanoparticle-linked drugs. Hyperthermia is induced by an alternating electromagnetic field (AMF) that induces heat from silica-coated superparamagnetic iron oxide nanoparticles (SPIONs). We show proof-of-principle of controlled release by the simultaneous disruption of the cargo cells and the controlled, AMF induced release of a toxin, which was covalently linked to silica-coated SPIONs via a thermo-sensitive linker. Cells that had not been loaded with SPIONs remain unaffected. Moreover, in a 3D co-culture model we demonstrate specific killing of associated tumour cells when employing a ratio as low as 1:40 (SPION-loaded macrophage: tumour cells). Overall, our results demonstrate that AMF induced drug release from macrophage-entrapped nanoparticles is tightly controlled and may be an attractive novel strategy for targeted drug release.
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Affiliation(s)
- Sami Ullah
- Model Systems for Infection and Immunity, Helmholtz Centre for Infection Research, Inhoffenstr. 7, Braunschweig 38124, Germany
| | - Katja Seidel
- Institute of Organic Chemistry and Centre of Biomolecular Drug Research (BMWZ), Leibniz Universität Hannover, Hannover, Germany
| | - Sibel Türkkan
- Institute of Organic Chemistry and Centre of Biomolecular Drug Research (BMWZ), Leibniz Universität Hannover, Hannover, Germany
| | - Dawid Peter Warwas
- Institute for Inorganic Chemistry, Leibniz University Hannover, Hannover, Germany
| | - Tatyana Dubich
- Model Systems for Infection and Immunity, Helmholtz Centre for Infection Research, Inhoffenstr. 7, Braunschweig 38124, Germany
| | - Manfred Rohde
- Central Facility for Microscopy, Helmholtz Centre for Infection Research, Braunschweig, Germany
| | - Hansjörg Hauser
- Scientific Strategy, Helmholtz Centre for Infection Research, Braunschweig, Germany
| | - Peter Behrens
- Institute for Inorganic Chemistry, Leibniz University Hannover, Hannover, Germany
| | - Andreas Kirschning
- Institute of Organic Chemistry and Centre of Biomolecular Drug Research (BMWZ), Leibniz Universität Hannover, Hannover, Germany
| | - Mario Köster
- Model Systems for Infection and Immunity, Helmholtz Centre for Infection Research, Inhoffenstr. 7, Braunschweig 38124, Germany
| | - Dagmar Wirth
- Model Systems for Infection and Immunity, Helmholtz Centre for Infection Research, Inhoffenstr. 7, Braunschweig 38124, Germany; Institute for Experimental Hematology, Medical University Hannover, Hannover, Germany.
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22
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Magnetic resonance imaging contrast enhancement in vitro and in vivo by octanuclear iron-oxo cluster-based agents. J Inorg Biochem 2018; 186:176-186. [PMID: 29957454 PMCID: PMC6943819 DOI: 10.1016/j.jinorgbio.2018.06.005] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/20/2018] [Revised: 05/24/2018] [Accepted: 06/09/2018] [Indexed: 02/03/2023]
Abstract
A water-soluble octanuclear cluster, [Fe8], was studied with regard to its properties as a potential contrast enhancing agent in magnetic resonance imaging (MRI) in magnetic fields of 1.3, 7.2 and 11.9 T and was shown to have transverse relaxivities r2 = 4.01, 10.09 and 15.83 mM s-1, respectively. A related hydrophobic [Fe8] cluster conjugated with 5 kDa hyaluronic acid (HA) was characterized by 57Fe-Mössbauer and MALDI-TOF mass spectroscopy, and was evaluated in aqueous solutions in vitro with regard to its contrast enhancing properties [r2 = 3.65 mM s-1 (1.3 T), 26.20 mM s-1 (7.2 T) and 52.18 mM s-1 (11.9 T)], its in vitro cellular cytotoxicity towards A-549 cells and COS-7 cells and its in vivo enhancement of T2-weighted images (4.7 T) of a human breast cancer xenografted on a nude mouse. The physiologically compatible [Fe8]-HA conjugate was i.v. injected to the tumor-bearing mouse, resulting in observable, heterogeneous signal change within the tumor, evident 15 min after injection and persisting for approximately 30 min. Both molecular [Fe8] and its HA-conjugate show a strong magnetic field dependence on r2, rendering them promising platforms for the further development of T2 MRI contrast agents in high and ultrahigh magnetic fields.
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23
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Balas M, Dumitrache F, Badea MA, Fleaca C, Badoi A, Tanasa E, Dinischiotu A. Coating Dependent In Vitro Biocompatibility of New Fe-Si Nanoparticles. NANOMATERIALS (BASEL, SWITZERLAND) 2018; 8:E495. [PMID: 29976868 PMCID: PMC6070796 DOI: 10.3390/nano8070495] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 05/24/2018] [Revised: 06/28/2018] [Accepted: 07/02/2018] [Indexed: 12/23/2022]
Abstract
Magnetic nanoparticles offer multiple utilization possibilities in biomedicine. In this context, the interaction with cellular structures and their biological effects need to be understood and controlled for clinical safety. New magnetic nanoparticles containing metallic/carbidic iron and elemental silicon phases were synthesized by laser pyrolysis using Fe(CO)₅ vapors and SiH₄ gas as Fe and Si precursors, then passivated and coated with biocompatible agents, such as l-3,4-dihydroxyphenylalanine (l-DOPA) and sodium carboxymethyl cellulose (CMC-Na). The resulting magnetic nanoparticles were characterized by XRD, EDS, and TEM techniques. To evaluate their biocompatibility, doses ranging from 0⁻200 µg/mL hybrid Fe-Si nanoparticles were exposed to Caco2 cells for 24 and 72 h. Doses below 50 μg/mL of both l-DOPA and CMC-Na-coated Fe-Si nanoparticles induced no significant changes of cellular viability or membrane integrity. The cellular internalization of nanoparticles was dependent on their dispersion in culture medium and caused some changes of F-actin filaments organization after 72 h. However, reactive oxygen species were generated after exposure to 25 and 50 μg/mL of both Fe-Si nanoparticles types, inducing the increase of intracellular glutathione level and activation of transcription factor Nrf2. At nanoparticles doses below 50 μg/mL, Caco2 cells were able to counteract the oxidative stress by activating the cellular protection mechanisms. We concluded that in vitro biological responses to coated hybrid Fe-Si nanoparticles depended on particle synthesis conditions, surface coating, doses and incubation time.
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Affiliation(s)
- Mihaela Balas
- Department of Biochemistry and Molecular Biology, University of Bucharest, 91⁻95 Splaiul Independenţei, 050095 Bucharest, sector 5, Romania.
| | - Florian Dumitrache
- National Institute for Lasers, Plasma and Radiation Physics (NILPRP), Atomistilor 409, 077125 Magurele, Romania.
| | - Madalina Andreea Badea
- Department of Biochemistry and Molecular Biology, University of Bucharest, 91⁻95 Splaiul Independenţei, 050095 Bucharest, sector 5, Romania.
| | - Claudiu Fleaca
- National Institute for Lasers, Plasma and Radiation Physics (NILPRP), Atomistilor 409, 077125 Magurele, Romania.
| | - Anca Badoi
- National Institute for Lasers, Plasma and Radiation Physics (NILPRP), Atomistilor 409, 077125 Magurele, Romania.
| | - Eugenia Tanasa
- Department of Oxide Materials and Nanomaterials, Faculty of Applied Chemistry and Materials Science, University Politehnica of Bucharest, Gh. Polizu 1-7, 11061 Bucharest, sector 1, Romania.
| | - Anca Dinischiotu
- Department of Biochemistry and Molecular Biology, University of Bucharest, 91⁻95 Splaiul Independenţei, 050095 Bucharest, sector 5, Romania.
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24
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Avitabile E, Bedognetti D, Ciofani G, Bianco A, Delogu LG. How can nanotechnology help the fight against breast cancer? NANOSCALE 2018; 10:11719-11731. [PMID: 29917035 DOI: 10.1039/c8nr02796j] [Citation(s) in RCA: 33] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/08/2023]
Abstract
In this review we provide a broad overview on the use of nanotechnology for the fight against breast cancer (BC). Nowadays, detection, diagnosis, treatment, and prevention may be possible thanks to the application of nanotechnology to clinical practice. Taking into consideration the different forms of BC and the disease status, nanomaterials can be designed to meet the most forefront objectives of modern therapy and diagnosis. We have analyzed in detail three main groups of nanomaterial applications for BC treatment and diagnosis. We have identified several types of drugs successfully conjugated with nanomaterials. We have analyzed the main important imaging techniques and all nanomaterials used to help the non-invasive, early detection of the lesions. Moreover, we have examined theranostic nanomaterials as unique tools, combining imaging, detection, and therapy for BC. This state of the art review provides a useful guide depicting how nanotechnology can be used to overcome the current barriers in BC clinical practice, and how it will shape the future scenario of treatments, prevention, and diagnosis, revolutionizing the current approaches, e.g., reducing the suffering related to chemotherapy.
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Affiliation(s)
- Elisabetta Avitabile
- Department of Chemistry and Pharmacy, University of Sassari, Via Vienna 2, 07100 Sassari, Italy.
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25
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Núñez C, Estévez SV, del Pilar Chantada M. Inorganic nanoparticles in diagnosis and treatment of breast cancer. J Biol Inorg Chem 2018; 23:331-345. [DOI: 10.1007/s00775-018-1542-z] [Citation(s) in RCA: 33] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/27/2017] [Accepted: 02/04/2018] [Indexed: 12/26/2022]
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26
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Rahman MA, Matsumura Y, Yano S, Ochiai B. pH-Responsive Charge-Conversional and Hemolytic Activities of Magnetic Nanocomposite Particles for Cell-Targeted Hyperthermia. ACS OMEGA 2018; 3:961-972. [PMID: 30023794 PMCID: PMC6045334 DOI: 10.1021/acsomega.7b01918] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/04/2017] [Accepted: 01/16/2018] [Indexed: 05/12/2023]
Abstract
Magnetic nanocomposite particle (MNP)-induced hyperthermia therapy has been restricted by inefficient cellular targeting. pH-responsive charge-conversional MNPs can enhance selective cellular uptake in acidic cells like tumors by sensing extracellular acidity based on their charge alteration. We have synthesized new, pH-induced charge-conversional, superparamagnetic, and single-cored Fe3O4 nanocomposite particles coated by N-itaconylated chitosan (NICS) cross-linked with ethylene glycol diglycidyl ether (EGDE) (Fe3O4-NICS-EGDE) using a simple, one-step chemical coprecipitation-coating process. The surface of the Fe3O4-NICS-EGDE nanocomposite particles was modified with ethanolamine (EA) via aza-Michael addition to enhance their buffering capacity, aqueous stability, and pH sensitivity. The designed Fe3O4-NICS-EGDE-EA nanocomposite particles showed pH-dependent charge-conversional properties, colloidal stability, and excellent hemocompatibility in physiological media. By contrast, the charge-conversional properties enabled microwave-induced hemolysis only under weakly acidic conditions. Therefore, the composite particles are highly feasible for magnetically induced and targeted cellular thermotherapeutic applications.
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Affiliation(s)
- Md. Abdur Rahman
- Department
of Chemistry and Chemical Engineering, Graduate School
of Science and Engineering and Department of Biochemical Engineering, Graduate
School of Science and Engineering, Yamagata
University, 4-3-16, Jonan, Yonezawa, Yamagata 992-8510, Japan
| | - Yoshimasa Matsumura
- Department
of Chemistry and Chemical Engineering, Graduate School
of Science and Engineering and Department of Biochemical Engineering, Graduate
School of Science and Engineering, Yamagata
University, 4-3-16, Jonan, Yonezawa, Yamagata 992-8510, Japan
| | - Shigekazu Yano
- Department
of Chemistry and Chemical Engineering, Graduate School
of Science and Engineering and Department of Biochemical Engineering, Graduate
School of Science and Engineering, Yamagata
University, 4-3-16, Jonan, Yonezawa, Yamagata 992-8510, Japan
| | - Bungo Ochiai
- Department
of Chemistry and Chemical Engineering, Graduate School
of Science and Engineering and Department of Biochemical Engineering, Graduate
School of Science and Engineering, Yamagata
University, 4-3-16, Jonan, Yonezawa, Yamagata 992-8510, Japan
- E-mail:
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27
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Absorbed doses in humans from 188 Re-Rituximab in the free form and bound to superparamagnetic iron oxide nanoparticles: Biodistribution study in mice. Appl Radiat Isot 2018; 131:96-102. [DOI: 10.1016/j.apradiso.2017.10.041] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/04/2017] [Revised: 10/12/2017] [Accepted: 10/23/2017] [Indexed: 11/18/2022]
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28
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Gao Z, Li G, Li X, Zhou J, Duan X, Chen J, Joshi BP, Kuick R, Khoury B, Thomas DG, Fields T, Sabel MS, Appelman HD, Zhou Q, Li H, Kozloff K, Wang TD. In vivo near-infrared imaging of ErbB2 expressing breast tumors with dual-axes confocal endomicroscopy using a targeted peptide. Sci Rep 2017; 7:14404. [PMID: 29089571 PMCID: PMC5663926 DOI: 10.1038/s41598-017-13735-z] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/16/2017] [Accepted: 09/27/2017] [Indexed: 02/08/2023] Open
Abstract
ErbB2 expression in early breast cancer can predict tumor aggressiveness and clinical outcomes in large patient populations. Accurate assessment with physical biopsy and conventional pathology can be limited by tumor heterogeneity. We aim to demonstrate real-time optical sectioning using a near-infrared labeled ErbB2 peptide that generates tumor-specific contrast in human xenograft breast tumors in vivo. We used IRDye800CW as the fluorophore, validated performance characteristics for specific peptide binding to cells in vitro, and investigated peak peptide uptake in tumors using photoacoustic tomography. We performed real-time optical imaging using a handheld dual-axes confocal fluorescence endomicroscope that collects light off-axis to reduce tissue scattering for greater imaging depths. Optical sections in either the vertical or horizontal plane were collected with sub-cellular resolution. Also, we found significantly greater peptide binding to pre-clinical xenograft breast cancer in vivo and to human specimens of invasive ductal carcinoma that express ErbB2 ex vivo. We used a scrambled peptide for control. Peptide biodistribution showed high tumor uptake by comparison with other organs to support safety. This novel integrated imaging strategy is promising for visualizing ErbB2 expression in breast tumors and serve as an adjunct during surgery to improve diagnostic accuracy, identify tumor margins, and stage early cancers.
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MESH Headings
- Animals
- Biomarkers, Tumor/metabolism
- Breast Neoplasms/diagnostic imaging
- Breast Neoplasms/metabolism
- Breast Neoplasms/pathology
- Carcinoma, Ductal, Breast/diagnostic imaging
- Carcinoma, Ductal, Breast/metabolism
- Carcinoma, Ductal, Breast/pathology
- Cell Line, Tumor
- Female
- Fluorescent Dyes/chemistry
- Mice, Nude
- Microscopy, Confocal/methods
- Neoplasm Transplantation
- Optical Imaging/methods
- Peptides/chemistry
- Photoacoustic Techniques/methods
- Receptor, ErbB-2/chemistry
- Receptor, ErbB-2/metabolism
- Tomography/methods
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Affiliation(s)
- Zhenghong Gao
- Dept of Internal Medicine, University of Michigan, Ann Arbor, MI, 48109, United States
| | - Gaoming Li
- Dept of Internal Medicine, University of Michigan, Ann Arbor, MI, 48109, United States
| | - Xue Li
- Dept of Internal Medicine, University of Michigan, Ann Arbor, MI, 48109, United States
| | - Juan Zhou
- Dept of Internal Medicine, University of Michigan, Ann Arbor, MI, 48109, United States
| | - Xiyu Duan
- Dept of Biomedical Engineering, University of Michigan, Ann Arbor, MI, 48109, United States
| | - Jing Chen
- Dept of Internal Medicine, University of Michigan, Ann Arbor, MI, 48109, United States
| | - Bishnu P Joshi
- Dept of Internal Medicine, University of Michigan, Ann Arbor, MI, 48109, United States
| | - Rork Kuick
- Dept of Biostatistics, University of Michigan, Ann Arbor, MI, 48109, United States
| | - Basma Khoury
- Dept of Internal Medicine, University of Michigan, Ann Arbor, MI, 48109, United States
- Dept of Orthopaedic Surgery, University of Michigan, Ann Arbor, MI, 48109, United States
| | - Dafydd G Thomas
- Dept of Pathology, University of Michigan, Ann Arbor, MI, 48109, United States
| | - Tina Fields
- Dept of Pathology, University of Michigan, Ann Arbor, MI, 48109, United States
| | - Michael S Sabel
- Dept of Surgery, University of Michigan, Ann Arbor, MI, 48109, United States
| | - Henry D Appelman
- Dept of Pathology, University of Michigan, Ann Arbor, MI, 48109, United States
| | - Quan Zhou
- Dept of Biomedical Engineering, University of Michigan, Ann Arbor, MI, 48109, United States
| | - Haijun Li
- Dept of Biomedical Engineering, University of Michigan, Ann Arbor, MI, 48109, United States
| | - Ken Kozloff
- Dept of Internal Medicine, University of Michigan, Ann Arbor, MI, 48109, United States
- Dept of Orthopaedic Surgery, University of Michigan, Ann Arbor, MI, 48109, United States
| | - Thomas D Wang
- Dept of Internal Medicine, University of Michigan, Ann Arbor, MI, 48109, United States.
- Dept of Biomedical Engineering, University of Michigan, Ann Arbor, MI, 48109, United States.
- Dept of Mechanical Engineering, University of Michigan, Ann Arbor, MI, 48109, United States.
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29
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Ding N, Sano K, Kanazaki K, Ohashi M, Deguchi J, Kanada Y, Ono M, Saji H. In Vivo HER2-Targeted Magnetic Resonance Tumor Imaging Using Iron Oxide Nanoparticles Conjugated with Anti-HER2 Fragment Antibody. Mol Imaging Biol 2017; 18:870-876. [PMID: 27351762 DOI: 10.1007/s11307-016-0977-2] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/31/2022]
Abstract
PURPOSE The feasibility of iron oxide nanoparticles (IONPs) conjugated with anti-epidermal growth factor receptor 2 (HER2) single-chain antibody (scFv-IONPs) as novel HER2-targeted magnetic resonance (MR) contrast agents was investigated. PROCEDURES The scFv-IONPs were prepared and identified. For in vitro MRI, NCI-N87 (HER2 high expression) and SUIT2 (low expression) cells were incubated with scFv-IONPs. For in vivo MRI, NCI-N87 and SUIT2 tumor-bearing mice were intravenously injected with scFv-IONPs and imaged before and 24 h post-injection. RESULTS The scFv-IONPs demonstrated high transverse relaxivity (296.3 s-1 mM-1) and affinity toward HER2 (KD = 11.7 nM). In the in vitro MRI, NCI-N87 cells treated with scFv-IONPs exhibited significant MR signal reduction (44.6 %) than SUIT2 cells (6.8 %). In the in vivo MRI, decrease of MR signals in NCI-N87 tumors (19.3 %) was more notable than that in SUIT2 tumors (6.2 %). CONCLUSIONS The scFv-IONPs enabled HER2-specific tumor MR imaging, suggesting the potential of scFv-IONPs as a robust HER2-targeted MR contrast agent.
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Affiliation(s)
- Ning Ding
- Department of Patho-Functional Bioanalysis, Graduate School of Pharmaceutical Sciences, Kyoto University, 46-29 Yoshida Shimoadachi-cho, Sakyo-ku, Kyoto, 606-8501, Japan
| | - Kohei Sano
- Department of Patho-Functional Bioanalysis, Graduate School of Pharmaceutical Sciences, Kyoto University, 46-29 Yoshida Shimoadachi-cho, Sakyo-ku, Kyoto, 606-8501, Japan.,Kyoto University Hospital, 54 Kawaharacho, Shogoin, Sakyo-ku, Kyoto, 606-8507, Japan
| | - Kengo Kanazaki
- Department of Patho-Functional Bioanalysis, Graduate School of Pharmaceutical Sciences, Kyoto University, 46-29 Yoshida Shimoadachi-cho, Sakyo-ku, Kyoto, 606-8501, Japan.,Medical Imaging Project, Corporate R&D Headquarters, Canon Inc., 3-30-2 Shimomaruko, Ohta-ku, Tokyo, 146-8501, Japan
| | - Manami Ohashi
- Department of Patho-Functional Bioanalysis, Graduate School of Pharmaceutical Sciences, Kyoto University, 46-29 Yoshida Shimoadachi-cho, Sakyo-ku, Kyoto, 606-8501, Japan
| | - Jun Deguchi
- Department of Patho-Functional Bioanalysis, Graduate School of Pharmaceutical Sciences, Kyoto University, 46-29 Yoshida Shimoadachi-cho, Sakyo-ku, Kyoto, 606-8501, Japan
| | - Yuko Kanada
- Department of Patho-Functional Bioanalysis, Graduate School of Pharmaceutical Sciences, Kyoto University, 46-29 Yoshida Shimoadachi-cho, Sakyo-ku, Kyoto, 606-8501, Japan
| | - Masahiro Ono
- Department of Patho-Functional Bioanalysis, Graduate School of Pharmaceutical Sciences, Kyoto University, 46-29 Yoshida Shimoadachi-cho, Sakyo-ku, Kyoto, 606-8501, Japan
| | - Hideo Saji
- Department of Patho-Functional Bioanalysis, Graduate School of Pharmaceutical Sciences, Kyoto University, 46-29 Yoshida Shimoadachi-cho, Sakyo-ku, Kyoto, 606-8501, Japan.
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30
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Abstract
Cancer treatment has been very challenging in recent decades. One of the most promising cancer treatment methods is hyperthermia, which increases the tumor temperature (41-45 °C). Magnetic nanoparticles have been widely used for selective targeting of cancer cells. In the present study, magnetic dextran-spermine nanoparticles, conjugated with Anti-HER2 antibody to target breast cancer cells were developed. The magnetic dextran-spermine nanoparticles (DMNPs) were prepared by ionic gelation, followed by conjugation of antibody to them using EDC-NHS method. Then the Prussian blue method was used to estimate the targeting ability and cellular uptake. Cytotoxicity assay by MTT showed that antibody-conjugated MNPs (ADMNPs) have no toxic effect on SKBR3 and human fibroblast cells. Finally, the hyperthermia was applied to show that synthesized ADMNPs, could increase the cancer cells temperature up to 45 °C and kill most of them without affecting normal cells. These observations proved that Anti-HER2 conjugated magnetic dextran-spermine nanoparticles can target and destroy cancer cells and are potentially suitable for cancer treatment.
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31
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Shaterabadi Z, Nabiyouni G, Soleymani M. High impact of in situ dextran coating on biocompatibility, stability and magnetic properties of iron oxide nanoparticles. MATERIALS SCIENCE & ENGINEERING. C, MATERIALS FOR BIOLOGICAL APPLICATIONS 2017; 75:947-956. [DOI: 10.1016/j.msec.2017.02.143] [Citation(s) in RCA: 66] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/30/2016] [Revised: 12/11/2016] [Accepted: 02/24/2017] [Indexed: 01/16/2023]
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32
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Falagan-Lotsch P, Grzincic EM, Murphy CJ. New Advances in Nanotechnology-Based Diagnosis and Therapeutics for Breast Cancer: An Assessment of Active-Targeting Inorganic Nanoplatforms. Bioconjug Chem 2017; 28:135-152. [DOI: 10.1021/acs.bioconjchem.6b00591] [Citation(s) in RCA: 74] [Impact Index Per Article: 9.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/29/2022]
Affiliation(s)
- Priscila Falagan-Lotsch
- Department
of Chemistry, University of Illinois at Urbana−Champaign, Urbana, Illinois 61801, United States
| | - Elissa M. Grzincic
- Department
of Chemistry, University of Illinois at Urbana−Champaign, Urbana, Illinois 61801, United States
| | - Catherine J. Murphy
- Department
of Chemistry, University of Illinois at Urbana−Champaign, Urbana, Illinois 61801, United States
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33
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Li R, Liu B, Gao J. The application of nanoparticles in diagnosis and theranostics of gastric cancer. Cancer Lett 2016; 386:123-130. [PMID: 27845158 DOI: 10.1016/j.canlet.2016.10.032] [Citation(s) in RCA: 46] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/12/2016] [Revised: 10/12/2016] [Accepted: 10/22/2016] [Indexed: 02/07/2023]
Abstract
Gastric cancer is the fourth most common cancer and the second leading cause of cancer related death worldwide. For the diagnosis of gastric cancer, apart from regular systemic imaging, the locoregional imaging is also of great importance. Moreover, there are still other ways for the detecting of gastric cancer, including the early detection of gastric cancer by endoscopy, the detection of gastric-cancer related biomarkers and the detection of circulating tumor cells (CTCs) of gastric cancer. However, conventional diagnostic methods are usually lack of specificity and sensitivity. Nanoparticles provide many benefits in the diagnosis of gastric cancer. Besides, nanoparticles are capable of integrating the functions of diagnosis and treatment together (theranostics). In this paper, we reviewed the applications of nanoparticles in diagnosis and theranostics of gastric cancer in the above mentioned aspects.
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Affiliation(s)
- Rutian Li
- The Comprehensive Cancer Center of Drum-Tower Hospital, Medical School of Nanjing University & Clinical Cancer Institute of Nanjing University, Nanjing, PR China; Nanjing Drum Tower Hospital, Clinical College of Nanjing Medical University, Nanjing, PR China
| | - Baorui Liu
- The Comprehensive Cancer Center of Drum-Tower Hospital, Medical School of Nanjing University & Clinical Cancer Institute of Nanjing University, Nanjing, PR China.
| | - Jiahui Gao
- The Comprehensive Cancer Center of Drum-Tower Hospital, Medical School of Nanjing University & Clinical Cancer Institute of Nanjing University, Nanjing, PR China; Nanjing Drum Tower Hospital, Clinical College of Nanjing Medical University, Nanjing, PR China
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34
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Huang J, Li Y, Orza A, Lu Q, Guo P, Wang L, Yang L, Mao H. Magnetic Nanoparticle Facilitated Drug Delivery for Cancer Therapy with Targeted and Image-Guided Approaches. ADVANCED FUNCTIONAL MATERIALS 2016; 26:3818-3836. [PMID: 27790080 PMCID: PMC5077153 DOI: 10.1002/adfm.201504185] [Citation(s) in RCA: 165] [Impact Index Per Article: 18.3] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/21/2023]
Abstract
With rapid advances in nanomedicine, magnetic nanoparticles (MNPs) have emerged as a promising theranostic tool in biomedical applications, including diagnostic imaging, drug delivery and novel therapeutics. Significant preclinical and clinical research has explored their functionalization, targeted delivery, controllable drug release and image-guided capabilities. To further develop MNPs for theranostic applications and clinical translation in the future, we attempt to provide an overview of the recent advances in the development and application of MNPs for drug delivery, specifically focusing on the topics concerning the importance of biomarker targeting for personalized therapy and the unique magnetic and contrast-enhancing properties of theranostic MNPs that enable image-guided delivery. The common strategies and considerations to produce theranostic MNPs and incorporate payload drugs into MNP carriers are described. The notable examples are presented to demonstrate the advantages of MNPs in specific targeting and delivering under image guidance. Furthermore, current understanding of delivery mechanisms and challenges to achieve efficient therapeutic efficacy or diagnostic capability using MNP-based nanomedicine are discussed.
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Affiliation(s)
- Jing Huang
- Department of Radiology and Imaging Sciences, Emory University School of Medicine, Atlanta, GA 30322, USA
| | - Yuancheng Li
- Department of Radiology and Imaging Sciences, Emory University School of Medicine, Atlanta, GA 30322, USA
| | - Anamaria Orza
- Department of Radiology and Imaging Sciences, Emory University School of Medicine, Atlanta, GA 30322, USA
| | - Qiong Lu
- Department of Pharmacy, The Second Xiangya Hospital of Central South University, Changsha, Hunan 410011, China
| | - Peng Guo
- Department of Biomedical Engineering, The City College of New York, New York, NY 10031, USA. Vascular Biology Program, Boston Children’s Hospital, Boston, MA 02115, USA
| | - Liya Wang
- Department of Radiology and Imaging Sciences, Emory University School of Medicine, Atlanta, GA 30322, USA
| | - Lily Yang
- Department of Surgery, Emory University School of Medicine, Atlanta, GA 30322, USA
| | - Hui Mao
- Department of Radiology and Imaging Sciences, Emory University School of Medicine, Atlanta, GA 30322, USA
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35
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Kalber TL, Ordidge KL, Southern P, Loebinger MR, Kyrtatos PG, Pankhurst QA, Lythgoe MF, Janes SM. Hyperthermia treatment of tumors by mesenchymal stem cell-delivered superparamagnetic iron oxide nanoparticles. Int J Nanomedicine 2016; 11:1973-83. [PMID: 27274229 PMCID: PMC4869665 DOI: 10.2147/ijn.s94255] [Citation(s) in RCA: 35] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/29/2022] Open
Abstract
Magnetic hyperthermia – a potential cancer treatment in which superparamagnetic iron oxide nanoparticles (SPIONs) are made to resonantly respond to an alternating magnetic field (AMF) and thereby produce heat – is of significant current interest. We have previously shown that mesenchymal stem cells (MSCs) can be labeled with SPIONs with no effect on cell proliferation or survival and that within an hour of systemic administration, they migrate to and integrate into tumors in vivo. Here, we report on some longer term (up to 3 weeks) post-integration characteristics of magnetically labeled human MSCs in an immunocompromized mouse model. We initially assessed how the size and coating of SPIONs dictated the loading capacity and cellular heating of MSCs. Ferucarbotran® was the best of those tested, having the best like-for-like heating capability and being the only one to retain that capability after cell internalization. A mouse model was created by subcutaneous flank injection of a combination of 0.5 million Ferucarbotran-loaded MSCs and 1.0 million OVCAR-3 ovarian tumor cells. After 2 weeks, the tumors reached ~100 µL in volume and then entered a rapid growth phase over the third week to reach ~300 µL. In the control mice that received no AMF treatment, magnetic resonance imaging (MRI) data showed that the labeled MSCs were both incorporated into and retained within the tumors over the entire 3-week period. In the AMF-treated mice, heat increases of ~4°C were observed during the first application, after which MRI indicated a loss of negative contrast, suggesting that the MSCs had died and been cleared from the tumor. This post-AMF removal of cells was confirmed by histological examination and also by a reduced level of subsequent magnetic heating effect. Despite this evidence for an AMF-elicited response in the SPION-loaded MSCs, and in contrast to previous reports on tumor remission in immunocompetent mouse models, in this case, no significant differences were measured regarding the overall tumor size or growth characteristics. We discuss the implications of these results on the clinical delivery of hyperthermia therapy to tumors and on the possibility that a preferred therapeutic route may involve AMF as an adjuvant to an autologous immune response.
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Affiliation(s)
- Tammy L Kalber
- Lungs for Living Research Centre, UCL Respiratory, University College London, UK; UCL Centre for Advanced Biomedical Imaging, Division of Medicine, University College London, UK
| | - Katherine L Ordidge
- Lungs for Living Research Centre, UCL Respiratory, University College London, UK; UCL Centre for Advanced Biomedical Imaging, Division of Medicine, University College London, UK
| | - Paul Southern
- Healthcare Biomagnetics Laboratory, University College London, London, UK
| | - Michael R Loebinger
- Lungs for Living Research Centre, UCL Respiratory, University College London, UK
| | - Panagiotis G Kyrtatos
- UCL Centre for Advanced Biomedical Imaging, Division of Medicine, University College London, UK; Healthcare Biomagnetics Laboratory, University College London, London, UK
| | | | - Mark F Lythgoe
- UCL Centre for Advanced Biomedical Imaging, Division of Medicine, University College London, UK
| | - Sam M Janes
- Lungs for Living Research Centre, UCL Respiratory, University College London, UK
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36
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Mandal S, Chaudhuri K. Engineered magnetic core shell nanoprobes: Synthesis and applications to cancer imaging and therapeutics. World J Biol Chem 2016; 7:158-167. [PMID: 26981204 PMCID: PMC4768120 DOI: 10.4331/wjbc.v7.i1.158] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/22/2015] [Revised: 09/23/2015] [Accepted: 12/04/2015] [Indexed: 02/05/2023] Open
Abstract
Magnetic core shell nanoparticles are composed of a highly magnetic core material surrounded by a thin shell of desired drug, polymer or metal oxide. These magnetic core shell nanoparticles have a wide range of applications in biomedical research, more specifically in tissue imaging, drug delivery and therapeutics. The present review discusses the up-to-date knowledge on the various procedures for synthesis of magnetic core shell nanoparticles along with their applications in cancer imaging, drug delivery and hyperthermia or cancer therapeutics. Literature in this area shows that magnetic core shell nanoparticle-based imaging, drug targeting and therapy through hyperthermia can potentially be a powerful tool for the advanced diagnosis and treatment of various cancers.
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37
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Tarvirdipour S, Vasheghani-Farahani E, Soleimani M, Bardania H. Functionalized magnetic dextran-spermine nanocarriers for targeted delivery of doxorubicin to breast cancer cells. Int J Pharm 2016; 501:331-41. [PMID: 26875475 DOI: 10.1016/j.ijpharm.2016.02.012] [Citation(s) in RCA: 32] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/17/2015] [Revised: 02/06/2016] [Accepted: 02/08/2016] [Indexed: 12/25/2022]
Abstract
In recent decades, targeted drug delivery systems for breast cancer treatment emerged as an ideal alternative and promising solution to reduce systemic side effects of chemotherapeutic agents. In this study, the preparation and characterization of cationic doxorubicin (DOX) loaded magnetic dextran-spermine (DEX-SP) nanocarriers (DEX-SP-DOX) by ionic gelation were fully investigated. Then, anti-HER2 as a monoclonal antibody (mAb) and targeting ligand was conjugated via EDC/NHS reagents. The binding was confirmed by Bradford assay and further assessments were carried out by size and zeta potential measurements. Cytotoxicity effect and internalization of magnetic nanocarriers were assessed by MTT and Prussian blue assays and transmission electron microscopy (TEM), respectively. DLS measurements indicated that the size of nanocarriers increased from 62 to 84 nm by conjugation of anti-HER2 to them. The in vitro release of DOX from mAb conjugated magnetic nanocarriers at pHs 5 and 7.4 was found to be 85 and 55.5%, respectively. The MTT and Prussian blue assays demonstrated enhanced and selective uptake of DEX-SP-DOX-mAb by SKBR cell (HER2 overexpressed cells) in comparison with unconjugated nanocarriers due to higher cellular binding. The TEM result also confirmed cellular internalization of DEX-SP-DOX-mAb magnetic nanocarriers. These results are very promising for targeted delivery of DOX to HER2 positive breast cancer cells.
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Affiliation(s)
- Shabnam Tarvirdipour
- Biomedical Division, Faculty of Chemical Engineering, Tarbiat Modares University, P.O. Box 14115-143, Tehran, Iran
| | - Ebrahim Vasheghani-Farahani
- Biomedical Division, Faculty of Chemical Engineering, Tarbiat Modares University, P.O. Box 14115-143, Tehran, Iran.
| | - Masoud Soleimani
- Department of Hematology, Faculty of Medical Sciences, Tarbiat Modares University, P.O. Box 14115-331, Tehran,Iran
| | - Hassan Bardania
- Cell and Molecular research Center, Yasuj University of Medical Sciences, Yasuj, Iran
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38
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Esfandiari N, Arzanani MK, Soleimani M, Kohi-Habibi M, Svendsen WE. A new application of plant virus nanoparticles as drug delivery in breast cancer. Tumour Biol 2016; 37:1229-36. [PMID: 26286831 DOI: 10.1007/s13277-015-3867-3] [Citation(s) in RCA: 40] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/11/2015] [Accepted: 07/29/2015] [Indexed: 10/23/2022] Open
Abstract
Nanoparticles based on non-pathogenic viruses have opened up a novel sector in nanotechnology. Viral nanoparticles based on plant viruses have clear advantages over any synthetic nanoparticles as they are biocompatible and biodegradable self-assembled and can be produced inexpensively on a large scale. From several such under-development platforms, only a few have been characterized in the target-specific drugs into the cells. Potato virus X is presented as a carrier of the chemotherapeutic drug Herceptin that is currently used as a targeted therapy in (HER2+) breast cancer patients. Here, we used nanoparticles formed from the potato virus X to conjugate the Herceptin (Trastuzumab) monoclonal antibody as a new option in specific targeting of breast cancer. Bioconjugation was performed by EDC/sulfo-N-hydroxysuccinimide (sulfo-NHS) in a two-step protocol. Then, the efficiency of conjugation was investigated by different methods, including sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE), Western blot, ELISA, Zetasizer, and transmission electron microscopy. SDS-PAGE and Western blot analysis confirmed an 82-kDa protein band that resulted from conjugation of potato virus X (PVX) coat protein (27 kDa) to heavy chain of Herceptin (55 kDa). Zeta potential values for conjugated particles, PVX, and HER were -7.05, -21.4, and -1.48, respectively. We investigated the efficiency of PVX-Herceptin to induce SK-OV-3 and SK-BR-3 cells (HER2 positive cell lines) apoptosis. We therefore counted cells and measured apoptosis by flow cytometry assay, then compared with Herceptin alone. Based on our data, we confirmed the conjugation of PVX and Herceptin. This study suggests that the PVX-Herceptin conjugates enable Herceptin to become more potential therapeutic tools.
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Affiliation(s)
- Neda Esfandiari
- Department of Micro and Nanotechnology, Technical University of Denmark, Ørsteds Plads, 2800 Kgs, Lyngby, Denmark.
- Department of Plant Protection, Faculty of Sciences and Plant Protection, Tehran University, Tehran, Iran.
| | - Mohsen Karimi Arzanani
- Division of Hematology, Department of Medicine, Karolinska Institute, Karolinska University Hospital, SE14186, Stockholm, Sweden
| | - Masoud Soleimani
- Department of Hematology, Faculty of Medical Science, Tarbiat Modares University, Tehran, Iran
| | - Mina Kohi-Habibi
- Department of Plant Protection, Faculty of Sciences and Plant Protection, Tehran University, Tehran, Iran
| | - Winnie E Svendsen
- Department of Micro and Nanotechnology, Technical University of Denmark, Ørsteds Plads, 2800 Kgs, Lyngby, Denmark
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Bakhtiary Z, Saei AA, Hajipour MJ, Raoufi M, Vermesh O, Mahmoudi M. Targeted superparamagnetic iron oxide nanoparticles for early detection of cancer: Possibilities and challenges. NANOMEDICINE-NANOTECHNOLOGY BIOLOGY AND MEDICINE 2015; 12:287-307. [PMID: 26707817 DOI: 10.1016/j.nano.2015.10.019] [Citation(s) in RCA: 100] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/04/2015] [Revised: 10/22/2015] [Accepted: 10/25/2015] [Indexed: 02/07/2023]
Abstract
UNLABELLED Nanomedicine, the integration of nanotechnological tools in medicine demonstrated promising potential to revolutionize the diagnosis and treatment of various human health conditions. Nanoparticles (NPs) have shown much promise in diagnostics of cancer, especially since they can accommodate targeting molecules on their surface, which search for specific tumor cell receptors upon injection into the blood stream. This concentrates the NPs in the desired tumor location. Furthermore, such receptor-specific targeting may be exploited for detection of potential metastases in an early stage. Some NPs, such as superparamagnetic iron oxide NPs (SPIONs), are also compatible with magnetic resonance imaging (MRI), which makes their clinical translation and application rather easy and accessible for tumor imaging purposes. Furthermore, multifunctional and/or theranostic NPs can be used for simultaneous imaging of cancer and drug delivery. In this review article, we will specifically focus on the application of SPIONs in early detection and imaging of major cancer types. FROM THE CLINICAL EDITOR Super-paramagnetic iron oxide nanoparticles (SPIONs) have been reported by many to be useful as an MRI contrast agent in the detection of tumors. To further enhance the tumor imaging, SPIONs can be coupled with tumor targeting motifs. In this article, the authors performed a comprehensive review on the current status of using targeted SPIONS in tumor detection and also the potential hurdles to overcome.
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Affiliation(s)
- Zahra Bakhtiary
- Research Center for Pharmaceutical Nanotechnology, Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Amir Ata Saei
- Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden
| | - Mohammad J Hajipour
- Persian Gulf Marine Biotechnology Research Center, The Persian Gulf Biomedical Sciences Research Institute, Bushehr University of Medical Sciences, Bushehr, Iran
| | - Mohammad Raoufi
- Department of New Materials and Biosystems, Max Planck Institute for Intelligent Systems, Stuttgart, Germany; Department of Nanotechnology & Nanotechnology Research Center, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran
| | - Ophir Vermesh
- Molecular Imaging Program at Stanford (MIPS), Department of Radiology, Stanford University, CA, USA
| | - Morteza Mahmoudi
- Department of Nanotechnology & Nanotechnology Research Center, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran; Division of Cardiovascular Medicine, Stanford University School of Medicine, Stanford, CA, USA; Cardiovascular Institute, Stanford University School of Medicine, Stanford, CA, USA.
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Abstract
Aim: To investigate the size-dependent lymphatic uptake of nanoparticles in mice with rapidly growing syngeneic tumors. Materials & methods: Mice were inoculated subcutaneously with EL4 lymphoma cells and on day 5 or day 6 of tumor growth, injected peritumorally with either 29 nm or 58 nm of ultra-small superparamagnetic iron oxide nanoparticles. Twenty-four hours later the animals were imaged using MRI. Results & conclusion: The larger of the two particles can only be detected in the lymph node when injected in animals with 6-day-old tumors while the 29 nm ultra-small superparamagnetic iron oxide nanoparticle is observed on both time points. Tumor mass greatly impacts the size of particles that are transported to the lymph nodes. This study aims to improve the way the spreading of certain forms of cancer is detected. The method, known as sentinel lymph node detection, locates and removes the first lymph node that drains the tumor to examine it for cancer cells. The authors want to improve the way this is done by using a new contrast agent based on nanoparticles. Two different sizes of particles were injected around the implanted tumors in mice and imaged with MRI. The results indicate that the mass of the tumor plays a crucial role in the transport of nanoparticles to the lymph node.
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Korchinski DJ, Taha M, Yang R, Nathoo N, Dunn JF. Iron Oxide as an MRI Contrast Agent for Cell Tracking. MAGNETIC RESONANCE INSIGHTS 2015; 8:15-29. [PMID: 26483609 PMCID: PMC4597836 DOI: 10.4137/mri.s23557] [Citation(s) in RCA: 29] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 06/03/2015] [Revised: 08/17/2015] [Accepted: 08/19/2015] [Indexed: 01/07/2023]
Abstract
Iron oxide contrast agents have been combined with magnetic resonance imaging for cell tracking. In this review, we discuss coating properties and provide an overview of ex vivo and in vivo labeling of different cell types, including stem cells, red blood cells, and monocytes/macrophages. Furthermore, we provide examples of applications of cell tracking with iron contrast agents in stroke, multiple sclerosis, cancer, arteriovenous malformations, and aortic and cerebral aneurysms. Attempts at quantifying iron oxide concentrations and other vascular properties are examined. We advise on designing studies using iron contrast agents including methods for validation.
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Affiliation(s)
- Daniel J. Korchinski
- Department of Radiology, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada.,Hotchkiss Brain Institute, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada
| | - May Taha
- Department of Radiology, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada
| | - Runze Yang
- Department of Radiology, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada.,Hotchkiss Brain Institute, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada
| | - Nabeela Nathoo
- Department of Radiology, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada.,Hotchkiss Brain Institute, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada
| | - Jeff F. Dunn
- Department of Radiology, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada.,Hotchkiss Brain Institute, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada.,Experimental Imaging Centre, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada.,CORRESPONDENCE:
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Yin C, Hong B, Gong Z, Zhao H, Hu W, Lu X, Li J, Li X, Yang Z, Fan Q, Yao Y, Huang W. Fluorescent oligo(p-phenyleneethynylene) contained amphiphiles-encapsulated magnetic nanoparticles for targeted magnetic resonance and two-photon optical imaging in vitro and in vivo. NANOSCALE 2015; 7:8907-8919. [PMID: 25916546 DOI: 10.1039/c5nr00806a] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/04/2023]
Abstract
Folate receptor-targeted multifunctional fluorescent magnetic nanoparticles (FMNPs) composed of cores containing iron oxide nanocrystals and amphiphilic oligo(p-phenyleneethynylene) shells with multimodal imaging capability were successfully prepared through a convenient hydrophobic encapsulation approach. The iron oxide nanoparticles in the core provided T2-weighted magnetic resonance imaging (MRI), whereas the amphiphilic oligomers on the surface of the nanoparticles introduced good water-solubility, biocompatibility, excellent fluorescent properties and cancer-targeting. These nanoparticles exhibited superparamagnetic properties with saturation magnetization (Ms) of 23 emu g(-1) and a transverse relaxivity rate of 140.89 mM(-1) s(-1). In vitro studies indicated that the dual-modal FMNPs can serve as an effective two-photon fluorescent and a magnetic probe to achieve the targeted imaging of Hela cells without obvious cytotoxicity. In vivo two-photon fluorescence and MRI results demonstrated that the FMNPs were able to preferentially accumulate in tumor tissues to allow dual-modal detection of tumors in a living body. These studies provided insight in developing novel multifunctional probes for multimodal imaging, which would play an important role for theranostics in biomedical science.
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Affiliation(s)
- Chao Yin
- Key Laboratory for Organic Electronics and Information Displays & Institute of Advanced Materials (IAM), Jiangsu National Synergetic Innovation Center for Advanced Materials (SICAM), Nanjing University of Posts & Telecommunications, 9 Wenyuan Road, Nanjing 210023, China.
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Polysaccharide-Coated Magnetic Nanoparticles for Imaging and Gene Therapy. BIOMED RESEARCH INTERNATIONAL 2015; 2015:959175. [PMID: 26078971 PMCID: PMC4452369 DOI: 10.1155/2015/959175] [Citation(s) in RCA: 50] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 07/22/2014] [Accepted: 08/20/2014] [Indexed: 02/08/2023]
Abstract
Today, nanotechnology plays a vital role in biomedical applications, especially for the diagnosis and treatment of various diseases. Among the many different types of fabricated nanoparticles, magnetic metal oxide nanoparticles stand out as unique and useful tools for biomedical applications, because of their imaging characteristics and therapeutic properties such as drug and gene carriers. Polymer-coated magnetic particles are currently of particular interest to investigators in the fields of nanobiomedicine and fundamental biomaterials. Theranostic magnetic nanoparticles that are encapsulated or coated with polymers not only exhibit imaging properties in response to stimuli, but also can efficiently deliver various drugs and therapeutic genes. Even though a large number of polymer-coated magnetic nanoparticles have been fabricated over the last decade, most of these have only been used for imaging purposes. The focus of this review is on polysaccharide-coated magnetic nanoparticles used for imaging and gene delivery.
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Recent progress in biomedical applications of Pluronic (PF127): Pharmaceutical perspectives. J Control Release 2015; 209:120-38. [PMID: 25921088 DOI: 10.1016/j.jconrel.2015.04.032] [Citation(s) in RCA: 263] [Impact Index Per Article: 26.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/25/2015] [Revised: 04/23/2015] [Accepted: 04/24/2015] [Indexed: 10/23/2022]
Abstract
Most of the administered anti-cancer drugs are hydrophobic in nature and are known to have poor water solubility, short residence time, rapid clearance from the body and systemic side effects. Polymeric-based targeted particulate carrier system has shown to directly deliver the encapsulated anti-cancer drug to the desired site of action and prevent the interaction of encapsulated drug with the normal cells. Pluronic F127 (PF127) has been widely investigated for its broad-range of therodiagnostic applications in biomedical and pharmaceutical sciences, but rapid dissolution in the physiological fluids, short residence time, rapid clearance, and weak mechanical strength are the main shortcomings that are associated with PF127 and have recently been overcome by making various modifications in the structure of PF127 notably through preparation of PF127-based mixed polymeric micelles, PF127-conjugated nanoparticles and PF127-based hydrophobically modified thermogels. In this article, we have briefly discussed the recent studies that have been conducted on various anti-cancer drugs using PF127 as nano-carrier modified with other copolymers and/or conjugated with magnetic nanoparticles. The key findings of these studies demonstrated that the modified form of PF127 can significantly increase the stability of incorporated hydrophobic drugs with enhanced in vitro cytotoxicity and cellular uptake of anti-cancer drugs. Moreover, the modified form of PF127 has also shown its therapeutic potentials as therodiagnostics in various types of tumors and cancers. Hence, it can be concluded that the modified form of PF127 exhibits significant therodiagnostic effects with increased tumor-specific delivery of anti-cancer drugs having minimal toxic effects as compared to PF127 alone and/or other copolymers.
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Sharifi S, Seyednejad H, Laurent S, Atyabi F, Saei AA, Mahmoudi M. Superparamagnetic iron oxide nanoparticles for in vivo molecular and cellular imaging. CONTRAST MEDIA & MOLECULAR IMAGING 2015; 10:329-55. [PMID: 25882768 DOI: 10.1002/cmmi.1638] [Citation(s) in RCA: 87] [Impact Index Per Article: 8.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/11/2014] [Revised: 01/30/2015] [Accepted: 02/06/2015] [Indexed: 12/16/2022]
Abstract
In the last decade, the biomedical applications of nanoparticles (NPs) (e.g. cell tracking, biosensing, magnetic resonance imaging (MRI), targeted drug delivery, and tissue engineering) have been increasingly developed. Among the various NP types, superparamagnetic iron oxide NPs (SPIONs) have attracted considerable attention for early detection of diseases due to their specific physicochemical properties and their molecular imaging capabilities. A comprehensive review is presented on the recent advances in the development of in vitro and in vivo SPION applications for molecular imaging, along with opportunities and challenges.
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Affiliation(s)
- Shahriar Sharifi
- Department of Biomaterials Science and Technology, University of Twente, The Netherlands
| | - Hajar Seyednejad
- Department of Bioengineering, Rice University, Houston, TX, 77005, USA
| | - Sophie Laurent
- Department of General, Organic, and Biomedical Chemistry, NMR and Molecular Imaging Laboratory, University of Mons, Avenue Maistriau 19, B-7000, Mons, Belgium.,CMMI - Center for Microscopy and Molecular Imaging, Rue Adrienne Bolland 8, B-6041, Gosselies, Belgium
| | - Fatemeh Atyabi
- Nanotechnology Research Center and Department of Nanotechnology, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran
| | - Amir Ata Saei
- Nanotechnology Research Center and Department of Nanotechnology, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran.,Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden
| | - Morteza Mahmoudi
- Nanotechnology Research Center and Department of Nanotechnology, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran.,Division of Cardiovascular Medicine, Department of Medicine, Stanford University School of Medicine, Stanford, CA, USA.,Cardiovascular Institute, Department of Medicine, Stanford University School of Medicine, Stanford, CA, USA
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46
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Kulhari H, Pooja D, Rompicharla SVK, Sistla R, Adams DJ. Biomedical Applications of Trastuzumab: As a Therapeutic Agent and a Targeting Ligand. Med Res Rev 2015; 35:849-76. [DOI: 10.1002/med.21345] [Citation(s) in RCA: 29] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
Affiliation(s)
- Hitesh Kulhari
- IICT-RMIT Research Centre, CSIR-Indian Institute of Chemical Technology; Hyderabad 500007 India
- Medicinal Chemistry & Pharmacology Division; CSIR-Indian Institute of Chemical Technology; Hyderabad 500007 India
- Health Innovations Research Institute; RMIT University; Melbourne VIC 3083 Australia
| | - Deep Pooja
- Medicinal Chemistry & Pharmacology Division; CSIR-Indian Institute of Chemical Technology; Hyderabad 500007 India
| | - Sri V. K. Rompicharla
- Medicinal Chemistry & Pharmacology Division; CSIR-Indian Institute of Chemical Technology; Hyderabad 500007 India
| | - Ramakrishna Sistla
- Medicinal Chemistry & Pharmacology Division; CSIR-Indian Institute of Chemical Technology; Hyderabad 500007 India
| | - David J. Adams
- Health Innovations Research Institute; RMIT University; Melbourne VIC 3083 Australia
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NDong C, Tate JA, Kett WC, Batra J, Demidenko E, Lewis LD, Hoopes PJ, Gerngross TU, Griswold KE. Tumor cell targeting by iron oxide nanoparticles is dominated by different factors in vitro versus in vivo. PLoS One 2015; 10:e0115636. [PMID: 25695795 PMCID: PMC4335054 DOI: 10.1371/journal.pone.0115636] [Citation(s) in RCA: 37] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/03/2014] [Accepted: 11/25/2014] [Indexed: 11/29/2022] Open
Abstract
Realizing the full potential of iron oxide nanoparticles (IONP) for cancer diagnosis and therapy requires selective tumor cell accumulation. Here, we report a systematic analysis of two key determinants for IONP homing to human breast cancers: (i) particle size and (ii) active vs passive targeting. In vitro, molecular targeting to the HER2 receptor was the dominant factor driving cancer cell association. In contrast, size was found to be the key determinant of tumor accumulation in vivo, where molecular targeting increased tumor tissue concentrations for 30 nm but not 100 nm IONP. Similar to the in vitro results, PEGylation did not influence in vivo IONP biodistribution. Thus, the results reported here indicate that the in vitro advantages of molecular targeting may not consistently extend to pre-clinical in vivo settings. These observations may have important implications for the design and clinical translation of advanced, multifunctional, IONP platforms.
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Affiliation(s)
- Christian NDong
- Thayer School of Engineering, Dartmouth, Hanover, NH, United States of America
| | - Jennifer A. Tate
- Thayer School of Engineering, Dartmouth, Hanover, NH, United States of America
| | - Warren C. Kett
- Thayer School of Engineering, Dartmouth, Hanover, NH, United States of America
| | - Jaya Batra
- Thayer School of Engineering, Dartmouth, Hanover, NH, United States of America
| | - Eugene Demidenko
- Department of Biostatistics and Medicine, The Geisel School of Medicine at Dartmouth, Lebanon, NH, United States of America
| | - Lionel D. Lewis
- Department of Biostatistics and Medicine, The Geisel School of Medicine at Dartmouth, Lebanon, NH, United States of America
| | - P. Jack Hoopes
- Department of Biostatistics and Medicine, The Geisel School of Medicine at Dartmouth, Lebanon, NH, United States of America
| | - Tillman U. Gerngross
- Thayer School of Engineering, Dartmouth, Hanover, NH, United States of America
- Department of Biological Sciences, Dartmouth, Hanover, NH, United States of America
- Department of Chemistry, Dartmouth, Hanover, NH, United States of America
| | - Karl E. Griswold
- Thayer School of Engineering, Dartmouth, Hanover, NH, United States of America
- Program in Molecular and Cellular Biology, Dartmouth, Hanover, NH, United States of America
- Department of Biological Sciences, Dartmouth, Hanover, NH, United States of America
- * E-mail:
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48
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Sivasubramanian M, Hsia Y, Lo LW. Nanoparticle-facilitated functional and molecular imaging for the early detection of cancer. Front Mol Biosci 2014; 1:15. [PMID: 25988156 PMCID: PMC4428449 DOI: 10.3389/fmolb.2014.00015] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/14/2014] [Accepted: 09/19/2014] [Indexed: 01/08/2023] Open
Abstract
Cancer detection in its early stages is imperative for effective cancer treatment and patient survival. In recent years, biomedical imaging techniques, such as magnetic resonance imaging, computed tomography and ultrasound have been greatly developed and have served pivotal roles in clinical cancer management. Molecular imaging (MI) is a non-invasive imaging technique that monitors biological processes at the cellular and sub-cellular levels. To achieve these goals, MI uses targeted imaging agents that can bind targets of interest with high specificity and report on associated abnormalities, a task that cannot be performed by conventional imaging techniques. In this respect, MI holds great promise as a potential therapeutic tool for the early diagnosis of cancer. Nevertheless, the clinical applications of targeted imaging agents are limited due to their inability to overcome biological barriers inside the body. The use of nanoparticles has made it possible to overcome these limitations. Hence, nanoparticles have been the subject of a great deal of recent studies. Therefore, developing nanoparticle-based imaging agents that can target tumors via active or passive targeting mechanisms is desirable. This review focuses on the applications of various functionalized nanoparticle-based imaging agents used in MI for the early detection of cancer.
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Affiliation(s)
- Maharajan Sivasubramanian
- Institute of Biomedical Engineering and Nanomedicine, National Health Research Institutes Zhunan, Taiwan
| | - Yu Hsia
- Institute of Biomedical Engineering and Nanomedicine, National Health Research Institutes Zhunan, Taiwan ; Institute of Biotechnology, National Tsing Hua University Hsinchu, Taiwan
| | - Leu-Wei Lo
- Institute of Biomedical Engineering and Nanomedicine, National Health Research Institutes Zhunan, Taiwan
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Zhou B, Zheng L, Peng C, Li D, Li J, Wen S, Shen M, Zhang G, Shi X. Synthesis and characterization of PEGylated polyethylenimine-entrapped gold nanoparticles for blood pool and tumor CT imaging. ACS APPLIED MATERIALS & INTERFACES 2014; 6:17190-9. [PMID: 25208617 DOI: 10.1021/am505006z] [Citation(s) in RCA: 92] [Impact Index Per Article: 8.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/12/2023]
Abstract
The synthesis and characterization of gold nanoparticles (AuNPs) entrapped within polyethylene glycol (PEG)-modified polyethylenimine (PEI) for blood pool and tumor computed tomography (CT) imaging are reported. In this approach, partially PEGylated PEI was used as a template for AuNP synthesis, followed by acetylating the PEI remaining surface amines. The synthesized PEGylated PEI-entrapped AuNPs (Au PENPs) were characterized via different methods. Our results reveal that the synthesized Au PENPs can be tuned to have an Au core size in a range of 1.9-4.6 nm and to be water-soluble, stable, and noncytotoxic in a studied concentration range. With a demonstrated better X-ray attenuation property than that of clinically used iodinated small molecular contrast agent (e.g., Omnipaque) and the prolonged half-decay time (11.2 h in rat) confirmed by pharmacokinetics studies, the developed PEGylated Au PENPs enabled efficient and enhanced blood pool CT imaging with imaging time up to 75 min. Likewise, thanks to the enhanced permeability and retention effect, the PEGylated Au PENPs were also able to be used as a contrast agent for effective CT imaging of a tumor model. With the proven organ biocompatibility by histological studies, the designed PEGylated Au PENPs may hold great promise to be used as contrast agents for CT imaging of a variety of biological systems. The significance of this study is that rather than the use of dendrimers as templates, cost-effective branched polymers (e.g., PEI) can be used as templates to generate functionalized AuNPs for CT imaging applications.
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Affiliation(s)
- Benqing Zhou
- College of Chemistry, Chemical Engineering and Biotechnology, Donghua University , Shanghai 201620, People's Republic of China
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50
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Zolata H, Abbasi Davani F, Afarideh H. Synthesis, characterization and theranostic evaluation of Indium-111 labeled multifunctional superparamagnetic iron oxide nanoparticles. Nucl Med Biol 2014; 42:164-70. [PMID: 25311750 DOI: 10.1016/j.nucmedbio.2014.09.007] [Citation(s) in RCA: 30] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/23/2014] [Revised: 09/19/2014] [Accepted: 09/24/2014] [Indexed: 01/11/2023]
Abstract
Indium-111 labeled, Trastuzumab-Doxorubicin Conjugated, and APTES-PEG coated magnetic nanoparticles were designed for tumor targeting, drug delivery, controlled drug release, and dual-modal tumor imaging. Superparamagnetic iron oxide nanoparticles (SPIONs) were synthesized by thermal decomposition method to obtain narrow size particles. To increase SPIONs circulation time in blood and decrease its cytotoxicity in healthy tissues, SPIONs surface was modified with 3-Aminopropyltriethoxy Silane (APTES) and then were functionalized with N-Hydroxysuccinimide (NHS) ester of Polyethylene Glycol Maleimide (NHS-PEG-Mal) to conjugate with thiolated 3,6,9,15-tetraazabicyclo[9.3.1]pentadeca-1(15),11,13-triene-3,6,9,-triacetic acid (PCTA) bifunctional chelator (BFC) and Trastuzumab antibody. In order to tumor SPECT/MR imaging, SPIONs were labeled with Indium-111 (T1/2=2.80d). NHS ester of monoethyl malonate (MEM-NHS) was used for conjugation of Doxorubicin (DOX) chemotherapeutic agent onto SPIONs surface. Mono-Ethyl Malonate allows DOX molecules to be attached to SPIONs via pH-sensitive hydrazone bonds which lead to controlled drug release in tumor region. Active and passive tumor targeting were achieved through incorporated anti-HER2 (Trastuzumab) antibody and EPR effect of solid tumors for nanoparticles respectively. In addition to in vitro assessments of modified SPIONs in SKBR3 cell lines, their theranostic effects were evaluated in HER2 + breast tumor bearing BALB/c mice via biodistribution study, dual-modal molecular imaging and tumor diameter measurements.
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Affiliation(s)
- Hamidreza Zolata
- AmirKabir University of Technology, Energy Engineering and Physics Faculty.
| | | | - Hossein Afarideh
- AmirKabir University of Technology, Energy Engineering and Physics Faculty
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