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Fan L, Yu Y, Shi K, Hu Y, Hou X, Sun W. Development of folic acid modified reduction-responsive micelles for the targeted release of sorafenib in liver cancer. Ther Deliv 2025:1-13. [PMID: 40448268 DOI: 10.1080/20415990.2025.2513223] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/04/2024] [Accepted: 05/27/2025] [Indexed: 06/02/2025] Open
Abstract
OBJECTIVE The presence of overexpressed folate-receptor and high concentration of glutathione (GSH) in liver cancer cells has been exploited and we have synthesized Folic acid-Dextran-Cystamine-Stearic acid (FDCS) for efficient and multifunctional delivery of the drug sorafenib (SAF) to enhance the anticancer effects. METHODS The characteristics of micelles such as physicochemical properties and in vitro release were investigated. The pharmacokinetic characteristics of the micelle and SAF groups in rats were investigated. In vitro and in vivo anti-tumor experiments were performed with HepG2 cells. RESULTS SAF-FDCS was successfully prepared and characterized. The cellular experiments showed that SAF-FDCS significantly enhanced the toxicity and inhibitory effects on HepG2 cells compared with free drug and the other micelles without smart response, and the uptake capacity of cellular HepG2 for SAF-FDCS was significantly higher than the groups without folic acid. Pharmacokinetic results showed that SAF-FDCS revealed a longer circulation time than free SAF. In addition, the tumor inhibition rate of SAF-FDCS in the subcutaneous graft tumor model of HepG2 cells was 84.6%, significantly higher than in other groups. CONCLUSIONS These results demonstrated the feasibility of SAF-FDCS micelles in inhibiting tumor growth and their superiority in anti-cancer effects compared to free drugs and normal micelles.
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Affiliation(s)
- Lixin Fan
- College of Pharmacy, Jiamusi University, Jiamusi, Heilongjiang, China
| | - Yang Yu
- College of Pharmacy, Jiamusi University, Jiamusi, Heilongjiang, China
| | - Kunpeng Shi
- Pharmacy Department, Jiamusi Infectious Disease Hospital, Jiamusi, Heilongjiang, China
| | - Yanqiu Hu
- College of Pharmacy, Jiamusi University, Jiamusi, Heilongjiang, China
| | - Xingyu Hou
- College of Pharmacy, Jiamusi University, Jiamusi, Heilongjiang, China
| | - Weitong Sun
- College of Pharmacy, Jiamusi University, Jiamusi, Heilongjiang, China
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2
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Zhao Y, Wang X, Yang X, Li J, Han B. Insights into the history and trends of nanotechnology for the treatment of hepatocellular carcinoma: a bibliometric-based visual analysis. Discov Oncol 2025; 16:484. [PMID: 40192866 PMCID: PMC11977073 DOI: 10.1007/s12672-025-02145-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/30/2024] [Accepted: 03/13/2025] [Indexed: 04/10/2025] Open
Abstract
BACKGROUND Nanotechnology has great potential and advantages in the treatment of hepatocellular carcinoma (HCC), but the research trends and future directions are not yet clear. OBJECTIVES Analyze the development trajectory, research hotspots, and future trends of nanotechnology and HCC research globally in the past 20 years, providing a more comprehensive and intuitive reference for researchers in this field. METHODS Retrieve relevant literature on nanotechnology and HCC research in the Web of Science (WOS) Core Collection database, and conduct bibliometric analysis using software such as CiteSpace, VOSviewer, and SCImago Graphica. RESULTS A total of 852 English publications meeting the criteria were retrieved from the WOS database, with an overall increasing trend in the number of publications and citation frequency over the years. China leads in the number of publications and international collaborations, followed by the USA and India. The most influential research institution is the Chinese Academy of Sciences, the most influential scholar/team is the Rahman, Mahfoozur team, and the journal with the most publications is the International Journal of Nanomedicine. A comprehensive analysis reveals that the current main research directions include new types of nanoparticles, targeted drug delivery systems, photothermal/photodynamic therapy, gene delivery systems, diagnostics, and imaging. It is anticipated that further collaboration among scholars, institutions, and countries will accelerate the development of nanotechnology in the field of HCC research. CONCLUSION This study provides an in-depth analysis of the research status and development trends of nanotechnology in treating HCC from a bibliometric perspective, offering possible guidance for researchers to explore hot topics and frontiers, select suitable journals, and partners in this field.
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Affiliation(s)
- Yulei Zhao
- College of Traditional Chinese Medicine, Shandong University of Traditional Chinese Medicine, Jinan, 250355, Shandong, China
| | - Xingxin Wang
- College of Acupuncture and Tuina, Shandong University of Traditional Chinese Medicine, Jinan, 250355, China
| | - Xiaoman Yang
- College of Traditional Chinese Medicine, Shandong University of Traditional Chinese Medicine, Jinan, 250355, Shandong, China
| | - Jiaheng Li
- College of Health, Shandong University of Traditional Chinese Medicine, Jinan, 250355, China
| | - Bingbing Han
- College of Traditional Chinese Medicine, Shandong University of Traditional Chinese Medicine, Jinan, 250355, Shandong, China.
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3
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Oryani MA, Nosrati S, Javid H, Mehri A, Hashemzadeh A, Karimi-Shahri M. Targeted cancer treatment using folate-conjugated sponge-like ZIF-8 nanoparticles: a review. NAUNYN-SCHMIEDEBERG'S ARCHIVES OF PHARMACOLOGY 2024; 397:1377-1404. [PMID: 37715816 DOI: 10.1007/s00210-023-02707-y] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/13/2023] [Accepted: 09/02/2023] [Indexed: 09/18/2023]
Abstract
ZIF-8 (zeolitic imidazolate framework-8) is a potential drug delivery system because of its unique properties, which include a large surface area, a large pore capacity, a large loading capacity, and outstanding stability under physiological conditions. ZIF-8 nanoparticles may be readily functionalized with targeting ligands for the identification and absorption of particular cancer cells, enhancing the efficacy of chemotherapeutic medicines and reducing adverse effects. ZIF-8 is also pH-responsive, allowing medication release in the acidic milieu of cancer cells. Because of its tunable structure, it can be easily functionalized to design cancer-specific targeted medicines. The delivery of ZIF-8 to cancer cells can be facilitated by folic acid-conjugation. Hence, it can bind to overexpressed folate receptors on the surface of cancer cells, which holds the promise of reducing unwanted deliveries. As a result of its importance in cancer treatment, the folate-conjugated ZIF-8 was the major focus of this review.
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Affiliation(s)
- Mahsa Akbari Oryani
- Department of Pathology, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Shamim Nosrati
- Department of Clinical Biochemistry, Faculty of Medicine, Azad Shahroud University, Shahroud, Iran
| | - Hossein Javid
- Department of Medical Laboratory Sciences, Varastegan Institute for Medical Sciences, Mashhad, Iran.
- Department of Clinical Biochemistry, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
- Surgical Oncology Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.
| | - Ali Mehri
- Endoscopic and Minimally Invasive Surgery Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Alireza Hashemzadeh
- Department of Clinical Biochemistry, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Mehdi Karimi-Shahri
- Department of Pathology, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
- Department of Pathology, School of Medicine, Gonabad University of Medical Sciences, Gonabad, Iran.
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Jiang X, Zhao Y, Sun S, Xiang Y, Yan J, Wang J, Pei R. Research development of porphyrin-based metal-organic frameworks: targeting modalities and cancer therapeutic applications. J Mater Chem B 2023. [PMID: 37305964 DOI: 10.1039/d3tb00632h] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 06/13/2023]
Abstract
Porphyrins are naturally occurring organic molecules that have attracted widespread attention for their potential in the field of biomedical research. Porphyrin-based metal-organic frameworks (MOFs) that utilize porphyrin molecules as organic ligands have gained attention from researchers due to their excellent results as photosensitizers in tumor photodynamic therapy (PDT). Additionally, MOFs hold significant promise and potential for other tumor therapeutic approaches due to their tunable size and pore size, excellent porosity, and ultra-high specific surface area. Active delivery of nanomaterials via targeted molecules for tumor therapy has demonstrated greater accumulation, lower drug doses, higher therapeutic efficacy, and reduced side effects relative to passive targeting through the enhanced permeation and retention effect (EPR). This paper presents a comprehensive review of the targeting methods employed by porphyrin-based MOFs in tumor targeting therapy over the past few years. It further discusses the applications of porphyrin-based MOFs for targeted cancer therapy through various therapeutic methods. The objective of this paper is to provide a valuable reference and source of ideas for targeted therapy using porphyrin-based MOF materials and to inspire further exploration of their potential in the field of cancer therapy.
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Affiliation(s)
- Xiang Jiang
- College of Mechanics and Materials, Hohai University, Nanjing, 210098, China.
- CAS Key Laboratory of Nano-Bio Interface, Suzhou Institute of Nano-Tech and Nano-Bionics, Chinese Academy of Sciences, Suzhou, 215123, China.
| | - Yuewu Zhao
- CAS Key Laboratory of Nano-Bio Interface, Suzhou Institute of Nano-Tech and Nano-Bionics, Chinese Academy of Sciences, Suzhou, 215123, China.
| | - Shengkai Sun
- CAS Key Laboratory of Nano-Bio Interface, Suzhou Institute of Nano-Tech and Nano-Bionics, Chinese Academy of Sciences, Suzhou, 215123, China.
| | - Ying Xiang
- CAS Key Laboratory of Nano-Bio Interface, Suzhou Institute of Nano-Tech and Nano-Bionics, Chinese Academy of Sciences, Suzhou, 215123, China.
| | - Jincong Yan
- CAS Key Laboratory of Nano-Bio Interface, Suzhou Institute of Nano-Tech and Nano-Bionics, Chinese Academy of Sciences, Suzhou, 215123, China.
| | - Jine Wang
- College of Mechanics and Materials, Hohai University, Nanjing, 210098, China.
- CAS Key Laboratory of Nano-Bio Interface, Suzhou Institute of Nano-Tech and Nano-Bionics, Chinese Academy of Sciences, Suzhou, 215123, China.
- Jiangxi Institute of Nanotechnology, Nanchang, 330200, China
| | - Renjun Pei
- CAS Key Laboratory of Nano-Bio Interface, Suzhou Institute of Nano-Tech and Nano-Bionics, Chinese Academy of Sciences, Suzhou, 215123, China.
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Elmehrath S, Nguyen HL, Karam SM, Amin A, Greish YE. BioMOF-Based Anti-Cancer Drug Delivery Systems. NANOMATERIALS (BASEL, SWITZERLAND) 2023; 13:953. [PMID: 36903831 PMCID: PMC10005089 DOI: 10.3390/nano13050953] [Citation(s) in RCA: 14] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 01/29/2023] [Revised: 02/19/2023] [Accepted: 03/03/2023] [Indexed: 06/18/2023]
Abstract
A variety of nanomaterials have been developed specifically for biomedical applications, such as drug delivery in cancer treatment. These materials involve both synthetic and natural nanoparticles and nanofibers of varying dimensions. The efficacy of a drug delivery system (DDS) depends on its biocompatibility, intrinsic high surface area, high interconnected porosity, and chemical functionality. Recent advances in metal-organic framework (MOF) nanostructures have led to the achievement of these desirable features. MOFs consist of metal ions and organic linkers that are assembled in different geometries and can be produced in 0, 1, 2, or 3 dimensions. The defining features of MOFs are their outstanding surface area, interconnected porosity, and variable chemical functionality, which enable an endless range of modalities for loading drugs into their hierarchical structures. MOFs, coupled with biocompatibility requisites, are now regarded as highly successful DDSs for the treatment of diverse diseases. This review aims to present the development and applications of DDSs based on chemically-functionalized MOF nanostructures in the context of cancer treatment. A concise overview of the structure, synthesis, and mode of action of MOF-DDS is provided.
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Affiliation(s)
- Sandy Elmehrath
- Department of Chemistry, United Arab Emirates University, Al-Ain 15551, United Arab Emirates
| | - Ha L. Nguyen
- Department of Chemistry University of California—Berkeley, Kavli Energy Nanoscience Institute at UC Berkeley, and Berkeley Global Science Institute, Berkeley, CA 94720, USA
- Joint UAEU−UC Berkeley Laboratories for Materials Innovations, United Arab Emirates University, Al-Ain 15551, United Arab Emirates
| | - Sherif M. Karam
- Department of Anatomy, United Arab Emirates University, Al-Ain 15551, United Arab Emirates
- Zayed Centre for Health Sciences, United Arab Emirates University, Al-Ain 15551, United Arab Emirates
| | - Amr Amin
- Zayed Centre for Health Sciences, United Arab Emirates University, Al-Ain 15551, United Arab Emirates
- Department of Biology, United Arab Emirates University, Al-Ain 15551, United Arab Emirates
| | - Yaser E. Greish
- Department of Chemistry, United Arab Emirates University, Al-Ain 15551, United Arab Emirates
- Joint UAEU−UC Berkeley Laboratories for Materials Innovations, United Arab Emirates University, Al-Ain 15551, United Arab Emirates
- Zayed Centre for Health Sciences, United Arab Emirates University, Al-Ain 15551, United Arab Emirates
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Masoudifar R, Pouyanfar N, Liu D, Ahmadi M, Landi B, Akbari M, Moayeri-Jolandan S, Ghorbani-Bidkorpeh F, Asadian E, Shahbazi MA. Surface engineered metal-organic frameworks as active targeting nanomedicines for mono- and multi-therapy. APPLIED MATERIALS TODAY 2022; 29:101646. [DOI: 10.1016/j.apmt.2022.101646] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/06/2025]
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Bunzen H, Jirák D. Recent Advances in Metal-Organic Frameworks for Applications in Magnetic Resonance Imaging. ACS APPLIED MATERIALS & INTERFACES 2022; 14:50445-50462. [PMID: 36239348 PMCID: PMC10749454 DOI: 10.1021/acsami.2c10272] [Citation(s) in RCA: 20] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 06/09/2022] [Accepted: 10/05/2022] [Indexed: 06/16/2023]
Abstract
Diagnostics is an important part of medical practice. The information required for diagnosis is typically collected by performing diagnostic tests, some of which include imaging. Magnetic resonance imaging (MRI) is one of the most widely used and effective imaging techniques. To improve the sensitivity and specificity of MRI, contrast agents are used. In this review, the usage of metal-organic frameworks (MOFs) and composite materials based on them as contrast agents for MRI is discussed. MOFs are crystalline porous coordination polymers. Due to their huge design variety and high density of metal ions, they have been studied as a highly promising class of materials for developing MRI contrast agents. This review highlights the most important studies and focuses on the progress of the field over the last five years. The materials are classified based on their design and structural properties into three groups: MRI-active MOFs, composite materials based on MOFs, and MRI-active compounds loaded in MOFs. Moreover, an overview of MOF-based materials for heteronuclear MRI including 129Xe and 19F MRI is given.
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Affiliation(s)
- Hana Bunzen
- Chair
of Solid State and Materials Chemistry, Institute of Physics, University of Augsburg, Universitätsstraße 1, D-86159 Augsburg, Germany
| | - Daniel Jirák
- Department
of Diagnostic and Interventional Radiology, Institute for Clinical and Experimental Medicine, Vídeňská1958/9, 140 21 Prague 4, Czech Republic
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8
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Feng Y, Wu W, Li M. Metal-organic frameworks for hepatocellular carcinoma therapy and mechanism. Front Pharmacol 2022; 13:1025780. [PMID: 36225574 PMCID: PMC9549350 DOI: 10.3389/fphar.2022.1025780] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/23/2022] [Accepted: 09/05/2022] [Indexed: 11/22/2022] Open
Abstract
In recent years, metal organic frameworks (MOFs) have attracted increasing attention in cancer therapy, because they can enhance the anticancer efficacy of photodynamic therapy (PDT), photothermal therapy (PTT), photoacoustic imaging, and drug delivery. Owing to stable chemical adjustability, MOFs can be used as carriers to provide excellent loading sites and protection for small-molecule drugs. In addition, MOFs can be used to combine with a variety of therapeutic drugs, including chemotherapeutics drugs, photosensitizers, and radiosensitizers, to efficiently deliver drugs to tumor tissue and achieve desired treatment. There is hardly any review regarding the application of MOFs in hepatocellular carcinoma. In this review, the design, structure, and potential applications of MOFs as nanoparticulate systems in the treatment of hepatocellular carcinoma are presented. Systematic Review Registration: website, identifier registration number
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Miclea LC, Mihailescu M, Tarba N, Brezoiu AM, Sandu AM, Mitran RA, Berger D, Matei C, Moisescu MG, Savopol T. Evaluation of intracellular distribution of folate functionalized silica nanoparticles using fluorescence and hyperspectral enhanced dark field microscopy. NANOSCALE 2022; 14:12744-12756. [PMID: 36000453 DOI: 10.1039/d2nr01821g] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/15/2023]
Abstract
Using nanoparticles as carriers for drug delivery systems has become a widely applied strategy in therapeutics and diagnostics. However, the pattern of their intracellular distribution is yet to be clarified. Here we present an in vitro study on the incorporation of mesoporous silica nanoparticles conjugated with folate and loaded with a cytotoxic drug, Irinotecan. The nanoparticles count and distribution within the cell frame were evaluated by means of enhanced dark field microscopy combined with hyperspectral imagery and 3D reconstructions from double-labeled fluorescent samples. An original post-processing procedure was developed to emphasize the nanoparticles' localization in 3D reconstruction of cellular compartments. By these means, it has been shown that the conjugation of mesoporous silica nanoparticles with folate increases the efficiency of nanoparticles entering the cell and their preferential localization in the close vicinity of the nucleus. As revealed by metabolic viability assays, the nanoparticles functionalized with folate enhance the cytotoxic efficiency of Irinotecan.
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Affiliation(s)
- Luminita Claudia Miclea
- Biophysics and Cellular Biotechnology Department, Excellence Center for Research in Biophysics and Cellular Biotechnology, Faculty of Medicine, University of Medicine and Pharmacy Carol Davila, 8 Eroii Sanitari Blvd., Bucharest, 050474, Romania.
| | - Mona Mihailescu
- Digital Holography Imaging and Processing Laboratory, Fundamental Sciences Applied in Engineering Research Center, Faculty of Applied Sciences, University "Politehnica" of Bucharest, 313 Splaiul Independentei, Bucharest, 060042, Romania.
| | - Nicolae Tarba
- Physics Department, Faculty of Applied Sciences, Doctoral School of Automatic Control and Computers, University "Politehnica" of Bucharest, 313 Splaiul Independentei, Bucharest, 060042, Romania
| | - Ana-Maria Brezoiu
- Department of Inorganic Chemistry, Physical-Chemistry & Electrochemistry, Faculty of Chemical Engineering and Biotechnologies, University "Politehnica" of Bucharest, 1-7 Polizu st., 11061, Bucharest, Romania
| | - Ana Maria Sandu
- CAMPUS Research Center, University "Politehnica" of Bucharest, 313 Splaiul Independentei, Bucharest, 060042, Romania
| | - Raul-Augustin Mitran
- "Ilie Murgulescu" Institute of Physical-Chemistry, Romanian Academy, 202 Splaiul Indepedenţei, Bucharest, 060021, Romania
| | - Daniela Berger
- Department of Inorganic Chemistry, Physical-Chemistry & Electrochemistry, Faculty of Chemical Engineering and Biotechnologies, University "Politehnica" of Bucharest, 1-7 Polizu st., 11061, Bucharest, Romania
| | - Cristian Matei
- Department of Inorganic Chemistry, Physical-Chemistry & Electrochemistry, Faculty of Chemical Engineering and Biotechnologies, University "Politehnica" of Bucharest, 1-7 Polizu st., 11061, Bucharest, Romania
| | - Mihaela Georgeta Moisescu
- Biophysics and Cellular Biotechnology Department, Excellence Center for Research in Biophysics and Cellular Biotechnology, Faculty of Medicine, University of Medicine and Pharmacy Carol Davila, 8 Eroii Sanitari Blvd., Bucharest, 050474, Romania.
| | - Tudor Savopol
- Biophysics and Cellular Biotechnology Department, Excellence Center for Research in Biophysics and Cellular Biotechnology, Faculty of Medicine, University of Medicine and Pharmacy Carol Davila, 8 Eroii Sanitari Blvd., Bucharest, 050474, Romania.
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10
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Liu Z, Li H, Tian Z, Liu X, Guo Y, He J, Wang Z, Zhou T, Liu Y. Porphyrin-Based Nanoparticles: A Promising Phototherapy Platform. Chempluschem 2022; 87:e202200156. [PMID: 35997087 DOI: 10.1002/cplu.202200156] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/02/2022] [Revised: 07/28/2022] [Indexed: 11/10/2022]
Abstract
Phototherapy, including photodynamic therapy and photothermal therapy, is an emerging form of non-invasive treatment. The combination of imaging technology and phototherapy is becoming an attractive development in the treatment of cancer, as it allows for highly effective therapeutic results through image-guided phototherapy. Porphyrins have attracted significant interest in the treatment and diagnosis of cancer due to their excellent phototherapeutic effects in phototherapy and their remarkable imaging capabilities in fluorescence imaging, magnetic resonance imaging and photoacoustic imaging. However, porphyrins suffer from poor water solubility, low near-infrared absorption and insufficient tumor accumulation. The development of nanotechnology provides an effective way to improve the bioavailability, phototherapeutic effect and imaging capability of porphyrins. This review highlights the research results of porphyrin-based small molecule nanoparticles in phototherapy and image-guided phototherapy in the last decade and discusses the challenges and directions for the development of porphyrin-based small molecule nanoparticles in phototherapy.
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Affiliation(s)
- Zhenhua Liu
- Institute of Pharmacy & Pharmacology Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study Hunan Provincial Key Laboratory of Tumor Microenvironment Responsive Drug Research, University of South China, Hengyang City, Hunan Province, 421001, P. R. China
| | - Hui Li
- Institute of Pharmacy & Pharmacology Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study Hunan Provincial Key Laboratory of Tumor Microenvironment Responsive Drug Research, University of South China, Hengyang City, Hunan Province, 421001, P. R. China
| | - Zejie Tian
- Institute of Pharmacy & Pharmacology Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study Hunan Provincial Key Laboratory of Tumor Microenvironment Responsive Drug Research, University of South China, Hengyang City, Hunan Province, 421001, P. R. China
| | - Xin Liu
- Institute of Pharmacy & Pharmacology Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study Hunan Provincial Key Laboratory of Tumor Microenvironment Responsive Drug Research, University of South China, Hengyang City, Hunan Province, 421001, P. R. China
| | - Yu Guo
- Institute of Pharmacy & Pharmacology Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study Hunan Provincial Key Laboratory of Tumor Microenvironment Responsive Drug Research, University of South China, Hengyang City, Hunan Province, 421001, P. R. China
| | - Jun He
- Institute of Chemistry & Chemical Engineering, University of South China, Hengyang City, Hunan Province, 421001, P.R. China
| | - Zhenyu Wang
- Institute of Chemistry & Chemical Engineering, University of South China, Hengyang City, Hunan Province, 421001, P.R. China
| | - Tao Zhou
- Institute of Pharmacy & Pharmacology Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study Hunan Provincial Key Laboratory of Tumor Microenvironment Responsive Drug Research, University of South China, Hengyang City, Hunan Province, 421001, P. R. China
| | - Yunmei Liu
- Institute of Pharmacy & Pharmacology Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study Hunan Provincial Key Laboratory of Tumor Microenvironment Responsive Drug Research, University of South China, Hengyang City, Hunan Province, 421001, P. R. China
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Zhao D, Cao J, Zhang L, Zhang S, Wu S. Targeted Molecular Imaging Probes Based on Magnetic Resonance Imaging for Hepatocellular Carcinoma Diagnosis and Treatment. BIOSENSORS 2022; 12:bios12050342. [PMID: 35624643 PMCID: PMC9138815 DOI: 10.3390/bios12050342] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 04/18/2022] [Revised: 05/09/2022] [Accepted: 05/11/2022] [Indexed: 11/30/2022]
Abstract
Hepatocellular carcinoma (HCC) is the sixth most commonly malignant tumor and the third leading cause of cancer-related death in the world, and the early diagnosis and treatment of patients with HCC is core in improving its prognosis. The early diagnosis of HCC depends largely on magnetic resonance imaging (MRI). MRI has good soft-tissue resolution, which is the international standard method for the diagnosis of HCC. However, MRI is still insufficient in the diagnosis of some early small HCCs and malignant nodules, resulting in false negative results. With the deepening of research on HCC, researchers have found many specific molecular biomarkers on the surface of HCC cells, which may assist in diagnosis and treatment. On the other hand, molecular imaging has progressed rapidly in recent years, especially in the field of cancer theranostics. Hence, the preparation of molecular imaging probes that can specifically target the biomarkers of HCC, combined with MRI testing in vivo, may achieve the theranostic purpose of HCC in the early stage. Therefore, in this review, taking MR imaging as the basic point, we summarized the recent progress regarding the molecular imaging targeting various types of biomarkers on the surface of HCC cells to improve the theranostic rate of HCC. Lastly, we discussed the existing obstacles and future prospects of developing molecular imaging probes as HCC theranostic nanoplatforms.
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Affiliation(s)
- Dongxu Zhao
- Department of Urology, The Third Affiliated Hospital of Shenzhen University (Luohu Hospital Group), Shenzhen 518000, China;
- Department of Interventional Radiology, The First Affiliated Hospital of Soochow University, Suzhou 215006, China
| | - Jian Cao
- Department of Gastroenterology, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Suzhou 215006, China;
| | - Lei Zhang
- Department of Interventional Radiology, The First Affiliated Hospital of Soochow University, Suzhou 215006, China
- Center of Interventional Radiology & Vascular Surgery, Department of Radiology, Zhongda Hospital, Medical School, Southeast University, Nanjing 210009, China
- Correspondence: (L.Z.); (S.Z.); (S.W.)
| | - Shaohua Zhang
- Department of Urology, The Third Affiliated Hospital of Shenzhen University (Luohu Hospital Group), Shenzhen 518000, China;
- Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou 510530, China
- Correspondence: (L.Z.); (S.Z.); (S.W.)
| | - Song Wu
- Department of Urology, The Third Affiliated Hospital of Shenzhen University (Luohu Hospital Group), Shenzhen 518000, China;
- Department of Urology, The Affiliated South China Hospital of Shenzhen University, Shenzhen University, Shenzhen 518000, China
- Correspondence: (L.Z.); (S.Z.); (S.W.)
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12
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Figueira F, Tomé JPC, Paz FAA. Porphyrin NanoMetal-Organic Frameworks as Cancer Theranostic Agents. Molecules 2022; 27:3111. [PMID: 35630585 PMCID: PMC9147750 DOI: 10.3390/molecules27103111] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/18/2022] [Revised: 05/05/2022] [Accepted: 05/09/2022] [Indexed: 02/06/2023] Open
Abstract
Metal-Organic Frameworks (MOFs) are hybrid multifunctional platforms that have found remarkable applications in cancer treatment and diagnostics. Independently, these materials can be employed in cancer treatment as intelligent drug carriers in chemotherapy, photothermal therapy, and photodynamic therapy; conversely, MOFs can further be used as diagnostic tools in fluorescence imaging, magnetic resonance imaging, computed tomography imaging, and photoacoustic imaging. One essential property of these materials is their great ability to fine-tune their composition toward a specific application by way of a judicious choice of the starting building materials (metal nodes and organic ligands). Moreover, many advancements were made concerning the preparation of these materials, including the ability to downsize the crystallites yielding nanoporous porphyrin MOFs (NMOFs) which are of great interest for clinical treatment and diagnostic theranostic tools. The usage of porphyrins as ligands allows a high degree of multifunctionality. Historically these molecules are well known for their reactive oxygen species formation and strong fluorescence characteristics, and both have proved helpful in cancer treatment and diagnostic tools. The anticipation that porphyrins in MOFs could prompt the resulting materials to multifunctional theranostic platforms is a reality nowadays with a series of remarkable and ground-breaking reports available in the literature. This is particularly remarkable in the last five years, when the scientific community witnessed rapid development in porphyrin MOFs theranostic agents through the development of imaging technologies and treatment strategies for cancer. This manuscript reviews the most relevant recent results and achievements in this particular area of interest in MOF chemistry and application.
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Affiliation(s)
- Flávio Figueira
- Department of Chemistry, CICECO—Aveiro Institute of Materials, University of Aveiro, 3810-193 Aveiro, Portugal;
| | - João P. C. Tomé
- Centro de Química Estrutural, Institute of Molecular Sciences, Departamento de Engenharia Química, Instituto Superior Técnico, Universidade de Lisboa, Av. Rovisco Pais, n° 1, 1049-001 Lisboa, Portugal;
| | - Filipe A. Almeida Paz
- Department of Chemistry, CICECO—Aveiro Institute of Materials, University of Aveiro, 3810-193 Aveiro, Portugal;
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13
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Shang Y, Zhang H, Cheng Y, Cao P, Cui J, Yin X, Fan S, Li Y. Fluorescent Imaging-Guided Chemo- and Photodynamic Therapy of Hepatocellular Carcinoma with HCPT@NMOFs-RGD Nanocomposites. Int J Nanomedicine 2022; 17:1381-1395. [PMID: 35369034 PMCID: PMC8964448 DOI: 10.2147/ijn.s353803] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/13/2021] [Accepted: 03/10/2022] [Indexed: 01/10/2023] Open
Abstract
Background Hepatocellular carcinoma (HCC), arising from hepatocytes, is the most common primary liver cancer. It is urgent to develop novel therapeutic approaches to improve the grim prognosis of advanced HCC. 10-hydroxycamptothecin (HCPT) has good antitumor activity in cells; however, its hydrophobicity limits its application in the chemotherapy of HCC. Recently, nanoscale porphyrin metal-organic frameworks have been used as drug carriers due to their low biotoxicity and photodynamic properties. Methods Nanoscale zirconium porphyrin metal-organic frameworks (NMOFs) were coated with arginine-glycine-aspartic acid (RGD) peptide to prepare NMOFs-RGD first. The HepG2 cell line, zebrafish embryos and larvae were used to test the biotoxicity and fluorescence imaging capability of NMOFs-RGD both in vitro and in vivo. Then, NMOFs were used as the skeleton, HCPT was assembled into the pores of NMOFs, while RGD peptide was wrapped around to synthesize a novel kind of nanocomposites, HCPT@NMOFs-RGD. The tissue distribution and chemo- and photodynamic therapeutic effects of HCPT@NMOFs-RGD were evaluated in a doxycycline-induced zebrafish HCC model and xenograft mouse model. Results NMOFs-RGD had low biotoxicity, good biocompatibility and excellent imaging capability. In HCC-bearing zebrafish, HCPT@NMOFs-RGD were specifically enriched in the tumor by binding specifically to integrin αvβ3 and led to a reduction in tumor volume. Moreover, the xenografts in mice were eliminated remarkably following HCPT@NMOFs-RGD treatment with laser irradiation, while little morphological change was found in other main organs. Conclusion The nanocomposites HCPT@NMOFs-RGD accomplish tumor targeting and play synergistic chemo- and photodynamic therapeutic effects on HCC, offering a novel imaging-guided drug delivery and theranostic platform.
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Affiliation(s)
- Yue Shang
- Institute of Radiation Medicine, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, People’s Republic of China
| | - Hui Zhang
- Shanghai Institute of Quality Inspection and Technical Research, Shanghai, People’s Republic of China
| | - Yajia Cheng
- Department of Pathology, Nankai University School of Medicine, Tianjin, People’s Republic of China
| | - Peipei Cao
- Department of Pathology, Nankai University School of Medicine, Tianjin, People’s Republic of China
| | - Jianlin Cui
- Department of Pathology, Nankai University School of Medicine, Tianjin, People’s Republic of China
| | - Xuebo Yin
- College of Chemistry and Chemical Engineering, Shanghai University of Engineering Science, Shanghai, People’s Republic of China
| | - Saijun Fan
- Institute of Radiation Medicine, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, People’s Republic of China
| | - Yuhao Li
- Beijing Geriatric Medical Research Center, Xuanwu Hospital, Capital Medical University, Beijing, People’s Republic of China
- Correspondence: Yuhao Li, Xuanwu Hospital, Capital Medical University, Beijing, 100053, People’s Republic of China, Tel +86-10-83198269, Email
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14
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Ma Y, Qu X, Liu C, Xu Q, Tu K. Metal-Organic Frameworks and Their Composites Towards Biomedical Applications. Front Mol Biosci 2022; 8:805228. [PMID: 34993235 PMCID: PMC8724581 DOI: 10.3389/fmolb.2021.805228] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/30/2021] [Accepted: 11/22/2021] [Indexed: 01/10/2023] Open
Abstract
Owing to their unique features, including high cargo loading, biodegradability, and tailorability, metal–organic frameworks (MOFs) and their composites have attracted increasing attention in various fields. In this review, application strategies of MOFs and their composites in nanomedicine with emphasis on their functions are presented, from drug delivery, therapeutic agents for different diseases, and imaging contrast agents to sensor nanoreactors. Applications of MOF derivatives in nanomedicine are also introduced. Besides, we summarize different functionalities related to MOFs, which include targeting strategy, biomimetic modification, responsive moieties, and other functional decorations. Finally, challenges and prospects are highlighted about MOFs in future applications.
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Affiliation(s)
- Yana Ma
- School of Basic Medical Sciences, Xi'an Key Laboratory of Immune Related Diseases, Xi'an Jiaotong University, Xi'an, China.,Key Laboratory of Environment and Genes Related to Diseases, Xi'an Jiaotong University, Ministry of Education, Xi'an, China
| | - Xianglong Qu
- Department of Hepatobiliary Surgery, the First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
| | - Cui Liu
- School of Basic Medical Sciences, Xi'an Key Laboratory of Immune Related Diseases, Xi'an Jiaotong University, Xi'an, China.,Key Laboratory of Environment and Genes Related to Diseases, Xi'an Jiaotong University, Ministry of Education, Xi'an, China
| | - Qiuran Xu
- Laboratory of Tumor Molecular Diagnosis and Individualized Medicine of Zhejiang Province, Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hangzhou Medical College, Hangzhou, China.,Research Center of Diagnosis and Treatment Technology for Hepatocellular Carcinoma of Zhejiang Province, Hangzhou, China
| | - Kangsheng Tu
- Department of Hepatobiliary Surgery, the First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
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15
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Liu Y, Jiang T, Liu Z. Metal-Organic Frameworks for Bioimaging: Strategies and Challenges. Nanotheranostics 2022; 6:143-160. [PMID: 34976590 PMCID: PMC8671950 DOI: 10.7150/ntno.63458] [Citation(s) in RCA: 24] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/04/2021] [Accepted: 08/14/2021] [Indexed: 12/17/2022] Open
Abstract
Metal-organic frameworks (MOFs), composited with metal ions and organic linkers, have become promising candidates in the biomedical field own to their unique properties, such as high surface area, pore-volume, tunable pore size, and versatile functionalities. In this review, we introduce and summarize the synthesis and characterization methods of MOFs, and their bioimaging applications, including optical bioimaging, magnetic resonance imaging (MRI), computed tomography (CT), and multi-mode. Furthermore, their bioimaging strategies, remaining challenges and future directions are discussed and proposed. This review provides valuable references for the designing of molecular bioimaging probes based on MOFs.
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Affiliation(s)
- Yanfei Liu
- Department of Pharmaceutical Engineering, College of Chemistry and Chemical Engineering, Central South University, Changsha, 410083, Hunan Province, P. R. China
| | - Ting Jiang
- Department of Pharmaceutical Engineering, College of Chemistry and Chemical Engineering, Central South University, Changsha, 410083, Hunan Province, P. R. China
| | - Zhenbao Liu
- Department of Pharmaceutics, Xiangya School of Pharmaceutical Sciences, Central South University, Changsha, 410013, Hunan Province, P. R. China
- Molecular Imaging Research Center of Central South University, Changsha 410008, Hunan, P. R. China
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16
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Zhu F, Wang BR, Zhu ZF, Wang SQ, Chai CX, Shang D, Li M. Photodynamic therapy: A next alternative treatment strategy for hepatocellular carcinoma? World J Gastrointest Surg 2021; 13:1523-1535. [PMID: 35070061 PMCID: PMC8727193 DOI: 10.4240/wjgs.v13.i12.1523] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/25/2021] [Revised: 06/20/2021] [Accepted: 09/08/2021] [Indexed: 02/06/2023] Open
Abstract
Liver cancer is one of the most common cancers in the world. Of all types of liver cancer, hepatocellular carcinoma (HCC) is known to be the most frequent primary liver malignancy and has seriously compromised the health status of the general population. Locoregional thermal ablation techniques such as radiofrequency and microwave ablation, have attracted attention in clinical practice as an alternative strategy for HCC treatment. However, their aggressive thermal effect may cause undesirable complications such as hepatic decompensation, hemorrhage, bile duct injury, extrahepatic organ injuries, and skin burn. In recent years, photodynamic therapy (PDT), a gentle locoregional treatment, has attracted attention in ablation therapy for patients with superficial or luminal tumors as an alternative treatment strategy. However, some inherent defects and extrinsic factors of PDT have limited its use in clinical practice for deep-seated HCC. In this contribution, the aim is to summarize the current status and challenges of PDT in HCC treatment and provide potential strategies to overcome these deficiencies in further clinical translational practice.
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Affiliation(s)
- Feng Zhu
- Department of Vascular Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, Hubei Province, China
| | - Bi-Rong Wang
- Department of Breast and Thyroid Surgery, Wuhan Fourth Hospital (Puai Hospital), Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei Province, China
| | - Zheng-Feng Zhu
- Department of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, Hubei Province, China
| | - Si-Qin Wang
- Department of Vascular Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, Hubei Province, China
| | - Chu-Xing Chai
- Department of Hepatobiliary Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, Hubei Province, China
| | - Dan Shang
- Department of Vascular Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, Hubei Province, China
| | - Min Li
- Department of Hepatobiliary Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, Hubei Province, China
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17
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Yang H, Wang N, Yang R, Zhang L, Jiang X. Folic Acid-Decorated β-Cyclodextrin-Based Poly(ε-caprolactone)-dextran Star Polymer with Disulfide Bond-Linker as Theranostic Nanoparticle for Tumor-Targeted MRI and Chemotherapy. Pharmaceutics 2021; 14:52. [PMID: 35056948 PMCID: PMC8778171 DOI: 10.3390/pharmaceutics14010052] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/11/2021] [Revised: 12/09/2021] [Accepted: 12/21/2021] [Indexed: 12/15/2022] Open
Abstract
β-cyclodextrin(βCD)-based star polymers have attracted much interest because of their unique structures and potential biomedical and biological applications. Herein, a well-defined folic acid (FA)-conjugated and disulfide bond-linked star polymer ((FA-Dex-SS)-βCD-(PCL)14) was synthesized via a couple reaction between βCD-based 14 arms poly(ε-caprolactone) (βCD-(PCL)14) and disulfide-containing α-alkyne dextran (alkyne-SS-Dex), and acted as theranostic nanoparticles for tumor-targeted MRI and chemotherapy. Theranostic nanoparticles were obtained by loading doxorubicin (DOX), and superparamagnetic iron oxide (SPIO) particles were loaded into the star polymer nanoparticles to obtain ((FA-Dex-SS)-βCD-(PCL)14@DOX-SPIO) theranostic nanoparticles. In vitro drug release studies showed that approximately 100% of the DOX was released from disulfide bond-linked theranostic nanoparticles within 24 h under a reducing environment in the presence of 10.0 mM GSH. DOX and SPIO could be delivered into HepG2 cells efficiently, owing to the folate receptor-mediated endocytosis process of the nanoparticles and glutathione (GSH), which triggered disulfide-bonds cleaving. Moreover, (FA-Dex-SS)-βCD-(PCL)14@DOX-SPIO showed strong MRI contrast enhancement properties. In conclusion, folic acid-decorated reduction-sensitive star polymeric nanoparticles are a potential theranostic nanoparticle candidate for tumor-targeted MRI and chemotherapy.
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Affiliation(s)
- Huikang Yang
- Department of Radiology, The Second Affiliated Hospital, School of Medicine, South China University of Technology, Yuexiu District, Guangzhou 510640, China; (H.Y.); (N.W.); (R.Y.)
| | - Nianhua Wang
- Department of Radiology, The Second Affiliated Hospital, School of Medicine, South China University of Technology, Yuexiu District, Guangzhou 510640, China; (H.Y.); (N.W.); (R.Y.)
| | - Ruimeng Yang
- Department of Radiology, The Second Affiliated Hospital, School of Medicine, South China University of Technology, Yuexiu District, Guangzhou 510640, China; (H.Y.); (N.W.); (R.Y.)
| | - Liming Zhang
- School of Materials Science and Engineering, Sun Yat-sen University, Haizhu District, Guangzhou 510275, China
| | - Xinqing Jiang
- Department of Radiology, The Second Affiliated Hospital, School of Medicine, South China University of Technology, Yuexiu District, Guangzhou 510640, China; (H.Y.); (N.W.); (R.Y.)
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18
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Bakrania A, Zheng G, Bhat M. Nanomedicine in Hepatocellular Carcinoma: A New Frontier in Targeted Cancer Treatment. Pharmaceutics 2021; 14:41. [PMID: 35056937 PMCID: PMC8779722 DOI: 10.3390/pharmaceutics14010041] [Citation(s) in RCA: 22] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/19/2021] [Revised: 12/17/2021] [Accepted: 12/22/2021] [Indexed: 02/07/2023] Open
Abstract
Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related death and is associated with a dismal median survival of 2-9 months. The fundamental limitations and ineffectiveness of current HCC treatments have led to the development of a vast range of nanotechnologies with the goal of improving the safety and efficacy of treatment for HCC. Although remarkable success has been achieved in nanomedicine research, there are unique considerations such as molecular heterogeneity and concomitant liver dysfunction that complicate the translation of nanotheranostics in HCC. This review highlights the progress, challenges, and targeting opportunities in HCC nanomedicine based on the growing literature in recent years.
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Affiliation(s)
- Anita Bakrania
- Toronto General Hospital Research Institute, Toronto, ON M5G 2C4, Canada;
- Ajmera Transplant Program, University Health Network, Toronto, ON M5G 2N2, Canada
- Princess Margaret Cancer Centre, University Health Network, Toronto, ON M5G 2C1, Canada;
| | - Gang Zheng
- Princess Margaret Cancer Centre, University Health Network, Toronto, ON M5G 2C1, Canada;
- Institute of Biomedical Engineering, University of Toronto, Toronto, ON M5S 3G9, Canada
- Department of Medical Biophysics, University of Toronto, Toronto, ON M5G 1L7, Canada
| | - Mamatha Bhat
- Toronto General Hospital Research Institute, Toronto, ON M5G 2C4, Canada;
- Ajmera Transplant Program, University Health Network, Toronto, ON M5G 2N2, Canada
- Division of Gastroenterology, Department of Medicine, University Health Network, Toronto, ON M5G 2C4, Canada
- Department of Medical Sciences, University of Toronto, Toronto, ON M5S 1A1, Canada
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19
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Fan Z, Zhuang C, Wang S, Zhang Y. Photodynamic and Photothermal Therapy of Hepatocellular Carcinoma. Front Oncol 2021; 11:787780. [PMID: 34950591 PMCID: PMC8688153 DOI: 10.3389/fonc.2021.787780] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/01/2021] [Accepted: 11/22/2021] [Indexed: 01/10/2023] Open
Abstract
Hepatocellular carcinoma (HCC) is the most common primary liver tumor. It is ranked the sixth most common neoplasm and the third most common cause of cancer mortality. At present, the most common treatment for HCC is surgery, but the 5-year recurrence rates are still high. Patients with early stage HCC with few nodules can be treated with resection or radiofrequency ablation (RFA); while for multinodular HCC, transarterial chemoembolization (TACE) has been the first-line treatment. In recent years, based on medical engineering cooperation, nanotechnology has been increasingly applied to the treatment of cancer. Photodynamic therapy and photothermal therapy are effective for cancer. This paper summarizes the latest progress of photodynamic therapy and photothermal therapy for HCC, with the aim of providing new ideas for the treatment of HCC.
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Affiliation(s)
- Zhe Fan
- Department of General Surgery, the Third People’s Hospital of Dalian, Dalian Medical University, Dalian, China
- Department of Central Laboratory, the Third People’s Hospital of Dalian, Dalian Medical University, Dalian, China
| | - Chengjun Zhuang
- Department of Critical Care Medicine, The Second Affiliated Hospital of Dalian Medical University, Dalian, China
| | - Shuang Wang
- Department of Endocrinology, The Second Affiliated Hospital of Dalian Medical University, Dalian, China
| | - Yewei Zhang
- Department of Hepatobiliary and Pancreatic Surgery, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, China
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20
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Alves SR, Calori IR, Tedesco AC. Photosensitizer-based metal-organic frameworks for highly effective photodynamic therapy. MATERIALS SCIENCE & ENGINEERING. C, MATERIALS FOR BIOLOGICAL APPLICATIONS 2021; 131:112514. [PMID: 34857293 DOI: 10.1016/j.msec.2021.112514] [Citation(s) in RCA: 32] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/23/2021] [Revised: 10/20/2021] [Accepted: 10/22/2021] [Indexed: 12/22/2022]
Abstract
Photodynamic therapy (PDT) uses a photosensitizer, molecular oxygen, and visible light as an alternative clinical protocol against located malignant tumors and other diseases. More recently, PDT has been combined to immunotherapy as a promising option to treat metastatic cancer. However, previous generations of photosensitizers (PSs) revealed clinical difficulties such as long-term skin photosensitivity (first generation), the need for drug delivery vehicles (second generation), and intracellular self-aggregation (third generation), which have generated a somewhat confusing scenario in PDT approaches and evolution. Recently, metal-organic frameworks (MOFs) with exceptionally high PS loading as a building unit of MOF framework have emerged as fourth-generation PS and presented outstanding outcomes under pre-clinical studies. For PS-based MOFs, the inorganic building unit (metal ions/clusters) plays an important role as a coadjuvant in PDT to alleviate hypoxia, to decrease antioxidant species, to yield ROS, or to act as a contrast agent for imaging-guided therapy. In this review, we intend to carry out a broad update on the recent history and the characteristics of PS-based MOFs from basic chemistry to the structure relationship with biological application in PDT. The details and variables that result in different photophysics, size, and morphology, are discussed. Also, we present an overview of the achievements on the pre-clinical assays in combination with other strategies, including alleviating hypoxia in solid tumors, chemotherapy, and the most recent immunotherapy for cancer.
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Affiliation(s)
- Samara Rodrigues Alves
- Department of Chemistry, Center of Nanotechnology and Tissue Engineering - Photobiology and Photomedicine Research Group, Faculty of Philosophy, Sciences and Letters of Ribeirão Preto, University of São Paulo, Ribeirão Preto, São Paulo 14040-901, Brazil.
| | - Italo Rodrigo Calori
- Department of Chemistry, Center of Nanotechnology and Tissue Engineering - Photobiology and Photomedicine Research Group, Faculty of Philosophy, Sciences and Letters of Ribeirão Preto, University of São Paulo, Ribeirão Preto, São Paulo 14040-901, Brazil.
| | - Antonio Claudio Tedesco
- Department of Chemistry, Center of Nanotechnology and Tissue Engineering - Photobiology and Photomedicine Research Group, Faculty of Philosophy, Sciences and Letters of Ribeirão Preto, University of São Paulo, Ribeirão Preto, São Paulo 14040-901, Brazil.
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21
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Du Y, Liu D, Du Y. Recent advances in hepatocellular carcinoma therapeutic strategies and imaging-guided treatment. J Drug Target 2021; 30:287-301. [PMID: 34727794 DOI: 10.1080/1061186x.2021.1999963] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/02/2023]
Abstract
Hepatocellular carcinoma (HCC) is one of the most common malignant cancer in the world, which greatly threatens human health. However, the routine treatment strategies for HCC have failed to specifically eradicate the tumorigenic cells, leading to the occurrence of metastasis and recurrence. To improve treatment efficacies, the development of novel effective technologies is urgently required. Recently, nanotechnologies have gained the extensive attention in cancer targeted therapy, which could provide a promising way for HCC clinical practice. However, a successful cancer management depends on accurate diagnosis of the tumour along with precise therapeutic protocol, thereby predicting the tumour response to existing therapies. The synergistic effect of targeted therapeutic systems and imaging approaches (also called 'imaging-guided cancer treatment') may establish a more effective platform for individual cancer care. This review outlines the recent advanced nano-targeted and -traceable therapeutic strategies for HCC management. The multifunctional nano agents that have both diagnosis and therapy abilities are highlighted. Finally, we conclude with our perspectives on the future development and challenges of HCC nanotheranostics.
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Affiliation(s)
- Yan Du
- Institute of Pharmaceutics, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, China
| | - Di Liu
- Institute of Pharmaceutics, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, China
| | - Yongzhong Du
- Institute of Pharmaceutics, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, China
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22
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Zhong Y, Bejjanki NK, Miao X, Weng H, Li Q, Zhang J, Liu T, Vannam R, Xie M. Synthesis and Photothermal Effects of Intracellular Aggregating Nanodrugs Targeting Nasopharyngeal Carcinoma. Front Bioeng Biotechnol 2021; 9:730925. [PMID: 34604188 PMCID: PMC8481884 DOI: 10.3389/fbioe.2021.730925] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/25/2021] [Accepted: 09/02/2021] [Indexed: 12/25/2022] Open
Abstract
Chemotherapy for the treatment of nasopharyngeal carcinoma (NPC) is usually associated with many side effects; therefore, its treatment options have not yet been completely resolved. Improving distribution to the targeted tumor region and enhancing the cellular uptake of drugs can efficiently alleviate the above adverse medical effects. Near-infrared (NIR) laser light-mediated photothermal therapy (PTT) and photodynamic therapy (PDT) are promising strategies for cancer treatment. In the present study, we developed an efficient multifunctional nanocluster with enhanced targeting and aggregation efficiency for PTT and PDT that is composed of a biocompatible folic acid (FA), indocyanine green (ICG) and 2-cyanobenzothiazole (CBT)-functionalized peptide labeled with an aldehyde sodium alginate-modified magnetic iron oxide nanoparticle (ASA-MNP)-based nanocarrier. FA can bind to folate receptors on cancer cell membranes to enhance nanocluster uptake. CBT-modified peptide can react with glutathione (GSH), which is typically present at higher levels in cancer cells, to form intracellular aggregates and increase the local concentration of the nanodrug. In in vitro studies, these nanodrugs displayed the desired uptake capacity by NPC cells and the ability to suppress the growth of cancer cells under laser irradiation. Animal studies validated that these nanodrugs are safe and nontoxic, efficiently accumulate in NPC tumor sites following injection via the caudal vein, and shows superior inhibition of tumor growth in a tumor-bearing mouse model upon near-infrared laser irradiation. The results indicate the potential application of the multifunctional nanoparticles (NPs), which can be used as a new method for the treatment of folate receptor-positive NPC.
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Affiliation(s)
- Ying Zhong
- Department of Otolaryngology-Head and Neck Surgery, Zhujiang Hospital, Southern Medical University, Guangzhou, China.,Department of Otolaryngology-Head and Neck Surgery, Zhuhai People's Hospital, Zhuhai, China
| | - Naveen Kumar Bejjanki
- Department of Otolaryngology-Head and Neck Surgery, Zhuhai People's Hospital, Zhuhai, China
| | - Xiangwan Miao
- Department of Otolaryngology-Head and Neck Surgery, Zhujiang Hospital, Southern Medical University, Guangzhou, China
| | - Huanhuan Weng
- Department of Thyroid Surgery, Shantou Central Hospital, Shantou, China
| | - Quanming Li
- Department of Otolaryngology-Head and Neck Surgery, Zhuhai People's Hospital, Zhuhai, China
| | - Juan Zhang
- Department of Otolaryngology-Head and Neck Surgery, Zhujiang Hospital, Southern Medical University, Guangzhou, China
| | - Tao Liu
- Department of Otolaryngology-Head and Neck Surgery, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China
| | - Raghu Vannam
- Piramal Pharma Solutions, Riverview, MI, United States
| | - Minqiang Xie
- Department of Otolaryngology-Head and Neck Surgery, Zhujiang Hospital, Southern Medical University, Guangzhou, China.,Department of Otolaryngology-Head and Neck Surgery, Zhuhai People's Hospital, Zhuhai, China
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23
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Sohrabi H, Javanbakht S, Oroojalian F, Rouhani F, Shaabani A, Majidi MR, Hashemzaei M, Hanifehpour Y, Mokhtarzadeh A, Morsali A. Nanoscale Metal-Organic Frameworks: Recent developments in synthesis, modifications and bioimaging applications. CHEMOSPHERE 2021; 281:130717. [PMID: 34020194 DOI: 10.1016/j.chemosphere.2021.130717] [Citation(s) in RCA: 36] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/09/2021] [Revised: 04/24/2021] [Accepted: 04/27/2021] [Indexed: 06/12/2023]
Abstract
Porous Metal-Organic Frameworks (MOFs) have emerged as eye-catching materials in recent years. They are widely used in numerous fields of chemistry thanks to their desirable properties. MOFs have a key role in the development of bioimaging platforms that are hopefully expected to effectually pave the way for accurate and selective detection and diagnosis of abnormalities. Recently, many types of MOFs have been employed for detection of RNA, DNA, enzyme activity and small-biomolecules, as well as for magnetic resonance imaging (MRI) and computed tomography (CT), which are valuable methods for clinical analysis. The optimal performance of the MOF in the bio-imaging field depends on the core structure, synthesis method and modifications processes. In this review, we have attempted to present crucial parameters for designing and achieving an efficient MOF as bioimaging platforms, and provide a roadmap for researchers in this field. Moreover, the influence of modifications/fractionalizations on MOFs performance has been thoroughly discussed and challenging problems have been extensively addressed. Consideration is mainly focused on the principal concepts and applications that have been achieved to modify and synthesize advanced MOFs for future applications.
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Affiliation(s)
- Hessamaddin Sohrabi
- Department of Analytical Chemistry, Faculty of Chemistry, University of Tabriz, Tabriz, Iran
| | - Siamak Javanbakht
- Faculty of Chemistry, Shahid Beheshti University, G.C., P.O. Box 19396-4716, Tehran, Iran
| | - Fatemeh Oroojalian
- Department of Advanced Sciences and Technologies in Medicine, School of Medicine, North Khorasan University of Medical Sciences, Bojnurd, Iran
| | - Farzaneh Rouhani
- Department of Chemistry, Faculty of Sciences, Tarbiat Modares University, P.O. Box 14115-175, Tehran, Iran
| | - Ahmad Shaabani
- Faculty of Chemistry, Shahid Beheshti University, G.C., P.O. Box 19396-4716, Tehran, Iran
| | - Mir Reza Majidi
- Department of Analytical Chemistry, Faculty of Chemistry, University of Tabriz, Tabriz, Iran
| | - Mahmoud Hashemzaei
- Department of Pharmacodynamics and Toxicology, School of Pharmacy, Zabol University of Medical Sciences, Zabol. Iran
| | - Younes Hanifehpour
- Department of Chemistry, Sayyed Jamaleddin Asadabadi University, Asadabad, Iran
| | - Ahad Mokhtarzadeh
- Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
| | - Ali Morsali
- Department of Chemistry, Faculty of Sciences, Tarbiat Modares University, P.O. Box 14115-175, Tehran, Iran.
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Hashemzadeh A, Drummen GPC, Avan A, Darroudi M, Khazaei M, Khajavian R, Rangrazi A, Mirzaei M. When metal-organic framework mediated smart drug delivery meets gastrointestinal cancers. J Mater Chem B 2021; 9:3967-3982. [PMID: 33908592 DOI: 10.1039/d1tb00155h] [Citation(s) in RCA: 19] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Cancers of the gastrointestinal tract constitute one of the most common cancer types worldwide and a ∼58% increase in the global number of cases has been estimated by IARC for the next twenty years. Recent advances in drug delivery technologies have attracted scientific interest for developing and utilizing efficient therapeutic systems. The present review focuses on the use of nanoscale MOFs (Nano-MOFs) as carriers for drug delivery and imaging purposes. In pursuit of significant improvements to current gastrointestinal cancer chemotherapy regimens, systems that allow multiple concomitant therapeutic options (polytherapy) and controlled release are highly desirable. In this sense, MOF-based nanotherapeutics represent a significant step towards achieving this goal. Here, the current state-of-the-art of interdisciplinary research and novel developments into MOF-based gastrointestinal cancer therapy are highlighted and reviewed.
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Affiliation(s)
- Alireza Hashemzadeh
- Department of Medical Physiology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
| | - Gregor P C Drummen
- (Bio)Nanotechnology and Hepato/Renal Pathobiology Programs, Bio&Nano Solutions-LAB3BIO, Bielefeld, Germany
| | - Amir Avan
- Metabolic Syndrome Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Majid Darroudi
- Nuclear Medicine Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.
| | - Majid Khazaei
- Department of Medical Physiology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran. and Metabolic Syndrome Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Ruhollah Khajavian
- Department of Chemistry, Faculty of Science, Ferdowsi University of Mashhad, Mashhad 9177948974, Iran.
| | | | - Masoud Mirzaei
- Department of Chemistry, Faculty of Science, Ferdowsi University of Mashhad, Mashhad 9177948974, Iran.
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Harvey PD, Plé J. Recent Advances in Nanoscale Metal-Organic Frameworks Towards Cancer Cell Cytotoxicity: An Overview. J Inorg Organomet Polym Mater 2021; 31:2715-2756. [PMID: 33994899 PMCID: PMC8114195 DOI: 10.1007/s10904-021-02011-3] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/29/2021] [Accepted: 04/19/2021] [Indexed: 02/03/2023]
Abstract
Abstract The fight against cancer has always been a prevalent research topic. Nanomaterials have the ability to directly penetrate cancer cells and potentially achieve minimally invasive, precise and efficient tumor annihilation. As such, nanoscale metal organic frameworks (nMOFs) are becoming increasingly attractive as potential therapeutic agents in the medical field due to their high structural variability, good biocompatibility, ease of surface functionalization as well as their porous morphologies with tunable cavity sizes. This overview addresses five different common strategies used to find cancer therapies, while summarizing the recent progress in using nMOFs as cytotoxic cancer cell agents largely through in vitro studies, although some in vivo investigations have also been reported. Chemo and targeted therapies rely on drug encapsulation and delivery inside the cell, whereas photothermal and photodynamic therapies depend on photosensitizers. Concurrently, immunotherapy actively induces the body to destroy the tumor by activating an immune response. By choosing the appropriate metal center, ligands and surface functionalization, nMOFs can be utilized in all five types of therapies. In the last section, the future prospects and challenges of nMOFs with respect to the various therapies will be presented and discussed. Graphic Abstract
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Affiliation(s)
- Pierre D. Harvey
- Département de Chimie, Université de Sherbrooke, Sherbrooke, PQ J1K 2R1 Canada
| | - Jessica Plé
- Département de Chimie, Université de Sherbrooke, Sherbrooke, PQ J1K 2R1 Canada
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Deng X, Shao Z, Zhao Y. Development of porphyrin and titanium dioxide sonosensitizers for sonodynamic cancer therapy. BIOMATERIALS TRANSLATIONAL 2021; 2:72-85. [PMID: 35837259 PMCID: PMC9255825 DOI: 10.3877/cma.j.issn.2096-112x.2021.01.009] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 08/25/2020] [Revised: 10/20/2020] [Accepted: 11/04/2020] [Indexed: 01/17/2023]
Abstract
Sonodynamic therapy for malignant tumours has gained much attention for its deep penetration effect and efficient tumour killing ability. The design, modification, and utilization of sonosensitizers are important aspects of sonodynamic therapy. As an essential factor in this process, highly effective sonosensitizers should be developed to facilitate the clinical applications of sonodynamic therapy. This review takes porphyrin- and titanium dioxide (TiO2)-based systems as representative organic and inorganic sonosensitizers respectively, and summarizes their characteristics and biological effects as sonodynamic therapy. Upon discovery of novel sonosensitizers, sonodynamic therapy becomes an efficient means of adjuvant therapy for the treatment of malignant tumours.
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Affiliation(s)
- Xiangyu Deng
- Department of Orthopaedic Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei Province, China,Division of Chemistry and Biological Chemistry, School of Physical and Mathematical Sciences, Nanyang Technological University, Singapore
| | - Zengwu Shao
- Department of Orthopaedic Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei Province, China,Corresponding authors: Zengwu Shao, ; Yanli Zhao,
| | - Yanli Zhao
- Division of Chemistry and Biological Chemistry, School of Physical and Mathematical Sciences, Nanyang Technological University, Singapore,Corresponding authors: Zengwu Shao, ; Yanli Zhao,
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Chen X, Li Y, Yao T, Jia R. Benefits of Zebrafish Xenograft Models in Cancer Research. Front Cell Dev Biol 2021; 9:616551. [PMID: 33644052 PMCID: PMC7905065 DOI: 10.3389/fcell.2021.616551] [Citation(s) in RCA: 35] [Impact Index Per Article: 8.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/12/2020] [Accepted: 01/11/2021] [Indexed: 12/14/2022] Open
Abstract
As a promising in vivo tool for cancer research, zebrafish have been widely applied in various tumor studies. The zebrafish xenograft model is a low-cost, high-throughput tool for cancer research that can be established quickly and requires only a small sample size, which makes it favorite among researchers. Zebrafish patient-derived xenograft (zPDX) models provide promising evidence for short-term clinical treatment. In this review, we discuss the characteristics and advantages of zebrafish, such as their transparent and translucent features, the use of vascular fluorescence imaging, the establishment of metastatic and intracranial orthotopic models, individual pharmacokinetics measurements, and tumor microenvironment. Furthermore, we introduce how these characteristics and advantages are applied other in tumor studies. Finally, we discuss the future direction of the use of zebrafish in tumor studies and provide new ideas for the application of it.
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Affiliation(s)
- Xingyu Chen
- Department of Ophthalmology, Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.,Shanghai Key Laboratory of Orbital Diseases and Ocular Oncology, Shanghai, China
| | - Yongyun Li
- Department of Ophthalmology, Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.,Shanghai Key Laboratory of Orbital Diseases and Ocular Oncology, Shanghai, China
| | - Tengteng Yao
- Department of Ophthalmology, Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.,Shanghai Key Laboratory of Orbital Diseases and Ocular Oncology, Shanghai, China
| | - Renbing Jia
- Department of Ophthalmology, Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.,Shanghai Key Laboratory of Orbital Diseases and Ocular Oncology, Shanghai, China
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Younis SA, Bhardwaj N, Bhardwaj SK, Kim KH, Deep A. Rare earth metal–organic frameworks (RE-MOFs): Synthesis, properties, and biomedical applications. Coord Chem Rev 2021. [DOI: 10.1016/j.ccr.2020.213620] [Citation(s) in RCA: 30] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
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Abstract
Metal–organic frameworks (MOFs) have shown a great potential in biomedicine due to their promising applications in different fields, including drug delivery, thermometry, theranostics etc. In this context, the development of magnetic sub-micrometric or nanometric MOFs through miniaturization approaches of magnetic MOFs up to the nanoscale still represents a crucial step to fabricate biomedical probes, especially in the field of theranostic nanomedicine. Miniaturization processes have to be properly designed to tailor the size and shape of particles and to retain magnetic properties and high porosity in the same material, fundamental prerequisites to develop smart nanocarriers integrating simultaneously therapeutic and contrast agents for targeted chemotherapy or other specific clinical use. An overview of current trends on the design of magnetic nanoMOFs in the field of biomedicine, with particular emphasis on theranostics and bioimaging, is herein envisioned.
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Younis SA, Lim DK, Kim KH, Deep A. Metalloporphyrinic metal-organic frameworks: Controlled synthesis for catalytic applications in environmental and biological media. Adv Colloid Interface Sci 2020; 277:102108. [PMID: 32028075 DOI: 10.1016/j.cis.2020.102108] [Citation(s) in RCA: 30] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/07/2019] [Revised: 01/09/2020] [Accepted: 01/20/2020] [Indexed: 01/10/2023]
Abstract
Recently, as a new sub-family of porous coordination polymers (PCPs), porphyrinic-MOFs (Porph-MOFs) with biomimetic features have been developed using porphyrin macrocycles as ligands and/or pillared linkers. The control over the coordination of the porphyrin ligand and its derivatives however remains a challenge for engineering new tunable Porph-MOF frameworks by self-assembly methods. The key challenges exist in the following respects: (i) collapse of the large open pores of Porph-MOFs during synthesis, (ii) deactivation of unsaturated metal-sites (UMCs) by axial coordination, and (iii) the tendency of both coordinated moieties (at peripheral meso- and beta-carbon sites) and the N4-pyridine core to coordinate with metal cations. In this respect, this review covers the advances in the design of Porph-MOFs relative to their counterpart covalent organic frameworks (Porph-COFs). The potential utility of custom-designed porphyrin/metalloporphyrins ligands is highlighted. Synthesis strategies of Porph-MOFs are also illustrated with modular design of hybrid guest@host composites (either Porph@MOFs or guest@Porph-MOFs) with exceptional topologies and stability. This review summarizes the synergistic benefits of coordinated porphyrin ligands and functional guest molecules in Porph-MOF composites for enhanced catalytic performance in various redox applications. This review shed lights on the engineering of new tunable hetero-metals open active sites within (metallo)porphyrin-MOFs as out-of-the-box platforms for enhanced catalytic processes in chemical and biological media.
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Affiliation(s)
- Sherif A Younis
- Department of Civil and Environmental Engineering, Hanyang University, 222 Wangsimni-Ro, Seoul 04763, Republic of Korea; Analysis and Evaluation Department, Egyptian Petroleum Research Institute (EPRI), Nasr City, 11727 Cairo, Egypt; Liquid Chromatography and Water Unit, EPRI-Central Laboratories, Nasr City, 11727 Cairo, Egypt
| | - Dong-Kwon Lim
- KU-KIST Graduate School of Converging Science and Technology, Korea University,145 Anam-ro, Seongbuk-gu, Seoul 02841, Republic of Korea
| | - Ki-Hyun Kim
- Department of Civil and Environmental Engineering, Hanyang University, 222 Wangsimni-Ro, Seoul 04763, Republic of Korea.
| | - Akash Deep
- Central Scientific Instruments Organization (CSIR-CSIO), Sector 30 C, Chandigarh 160030, India.
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Yang D, Ji F, Li Y, Jiao Y, Fang X. GPSM2 Serves as an Independent Prognostic Biomarker for Liver Cancer Survival. Technol Cancer Res Treat 2020; 19:1533033820945817. [PMID: 32812493 PMCID: PMC7440740 DOI: 10.1177/1533033820945817] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/20/2019] [Revised: 05/22/2020] [Accepted: 06/19/2020] [Indexed: 12/26/2022] Open
Abstract
BACKGROUND AND OBJECTIVE Liver cancer is a malignancy with a poor prognosis. G protein signaling modulator 2 is mainly related to cell division and cell cycle regulation. In this review, the relationship between G protein signaling modulator 2 and clinical characteristics of patients with liver cancer has been explored, especially with respect to its prognostic value. METHODS G protein signaling modulator 2 messenger RNA expression and clinicopathological characteristics of patients with liver cancer were obtained from The Cancer Genome Atlas. The expression level of G protein signaling modulator 2 RNA-Seq was validated by using Gene Expression Omnibus. Chi-square test was performed to evaluate the relationship between G protein signaling modulator 2 expression and clinical characteristics. The threshold value of G protein signaling modulator 2 in the diagnosis of liver cancer was evaluated by a receiver-operating characteristic curve. Cox regression analysis and Kaplan-Meier curves were performed to evaluate the relationship between G protein signaling modulator 2 and liver cancer prognosis, which included overall and residual-free survival, and explored the prognostic value of G protein signaling modulator 2. Liver cancer survival analyses were validated by using the data of G protein signaling modulator 2 RNA-Seq from the International Cancer Genome Consortium. RESULTS The expression level of G protein signaling modulator 2 messenger RNA was remarkably higher in liver cancer than that in healthy tissues (P < 2.2 × e-16), which was also validated by data from the GSE14520 database. In addition, high G protein signaling modulator 2 expression significantly correlated with histological grade (P = .020), vital status (P < .001), clinical (P = .001), and T stage (P = .001). The receiver-operating characteristic curves showed G protein signaling modulator 2 to be an advantageous diagnostic molecule for liver cancer (area under curve = 0.893). Furthermore, the results of Cox analysis and Kaplan-Meier curves suggested that the upregulation of G protein signaling modulator 2 expression is linked to poor prognosis and G protein signaling modulator 2 messenger RNA could be an independent predictor for liver cancer, which was validated by data from the International Cancer Genome Consortium database. CONCLUSIONS G protein signaling modulator 2 messenger RNA was overexpressed in liver cancer, and G protein signaling modulator 2 is an independent prognostic factor. G protein signaling modulator 2 is expected to be a treatment target for cancer.
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Affiliation(s)
- Dingquan Yang
- Department of Gastrointestinal Colorectal and Anal Surgery, China-Japan Union Hospital of Jilin University, Changchun, Jilin, China
| | - Fujian Ji
- Department of Gastrointestinal Colorectal and Anal Surgery, China-Japan Union Hospital of Jilin University, Changchun, Jilin, China
| | - Yanqing Li
- Department of Pathophysiology, College of Basic Medical Sciences, Jilin University, Changchun, Jilin, China
| | - Yan Jiao
- Department of Hepatobiliary and Pancreatic Surgery, The First Hospital of Jilin University, Changchun, Jilin, China
| | - Xuedong Fang
- Department of Gastrointestinal Colorectal and Anal Surgery, China-Japan Union Hospital of Jilin University, Changchun, Jilin, China
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Li J, Zhang Y, Cai C, Rong X, Shao M, Li J, Yang C, Yu G. Collaborative assembly of doxorubicin and galactosyl diblock glycopolymers for targeted drug delivery of hepatocellular carcinoma. Biomater Sci 2019; 8:189-200. [PMID: 31821399 DOI: 10.1039/c9bm01604j] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
Hepatocellular carcinoma (HCC) patients suffer from severe pain due to the serious systemic side effects and low efficiency of chemotherapeutic drugs, and it is important to develop novel drug delivery systems to circumvent these issues. In this study, a series of galactose-based glycopolymers, poly(N-(prop-2-enoyl)-β-d-galactopyranosylamine)-b-poly(N-isopropyl acrylamide) (pGal(OH)-b-pNIPAA), were prepared through a sequential reversible addition-fragmentation chain transfer (RAFT) polymerization and tetrabutylammonium hydroxide (TBAOH)-mediated removal of acetyl groups. Hydrophilic doxorubicin hydrochloride was introduced to undergo collaborative assembly with poly(N-(prop-2-enoyl)-β-d-peracetylated galactosamine)-b-poly(N-isopropyl acrylamide) (pGal(Ac)-b-pNIPAA) via TBAOH treatment. pGal-b-pNIPAA/doxorubicin (DOX) delivery nanoparticles (GND NPs) formed by collaborative assembly were fully characterized by NMR, TEM and FT-IR, indicating the well-controlled formation of particles with uniform size and high efficiency in terms of drug loading and encapsulation compared with conventional adsorption methods. Meanwhile, the GND NPs were observed to be rapidly disintegrated under acidic conditions and resulted in an increased release of DOX. Cellular experiments showed that pGal-b-pNIPAA/DOX is apparently an asialoglycoprotein receptor (ASGPR)-mediated target of HCC, resulting in enhanced cellular uptake to HepG2 cells and anti-tumor efficacy in vitro. Furthermore, GND NPs III exerted more sustainable and effective anti-tumor effects compared to free DOX on a transgenic zebrafish TO(KrasG12V) model in vivo. These results indicated that the biocompatible nanomaterials developed by collaborative assembly with galactosyl diblock glycopolymers and DOX may serve as a promising candidates for targeting therapy of HCC.
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Affiliation(s)
- Jianghua Li
- Key Laboratory of Marine Drugs, Ministry of Education & Shandong Provincial Key Laboratory of Glycoscience and Glycotechnology, School of Medicine and Pharmacy, Ocean University of China, Qingdao 266003, China.
| | - Yang Zhang
- Key Laboratory of Marine Drugs, Ministry of Education & Shandong Provincial Key Laboratory of Glycoscience and Glycotechnology, School of Medicine and Pharmacy, Ocean University of China, Qingdao 266003, China.
| | - Chao Cai
- Key Laboratory of Marine Drugs, Ministry of Education & Shandong Provincial Key Laboratory of Glycoscience and Glycotechnology, School of Medicine and Pharmacy, Ocean University of China, Qingdao 266003, China. and Laboratory for Marine Drugs and Bioproducts, Pilot National Laboratory for Marine Science and Technology (Qingdao), Qingdao 266237, China
| | - Xiaozhi Rong
- Key Laboratory of Marine Drugs, Ministry of Education & Shandong Provincial Key Laboratory of Glycoscience and Glycotechnology, School of Medicine and Pharmacy, Ocean University of China, Qingdao 266003, China. and Laboratory for Marine Drugs and Bioproducts, Pilot National Laboratory for Marine Science and Technology (Qingdao), Qingdao 266237, China
| | - Meng Shao
- Key Laboratory of Marine Drugs, Ministry of Education & Shandong Provincial Key Laboratory of Glycoscience and Glycotechnology, School of Medicine and Pharmacy, Ocean University of China, Qingdao 266003, China.
| | - Jiarui Li
- Key Laboratory of Marine Drugs, Ministry of Education & Shandong Provincial Key Laboratory of Glycoscience and Glycotechnology, School of Medicine and Pharmacy, Ocean University of China, Qingdao 266003, China.
| | - Chendong Yang
- Key Laboratory of Marine Drugs, Ministry of Education & Shandong Provincial Key Laboratory of Glycoscience and Glycotechnology, School of Medicine and Pharmacy, Ocean University of China, Qingdao 266003, China.
| | - Guangli Yu
- Key Laboratory of Marine Drugs, Ministry of Education & Shandong Provincial Key Laboratory of Glycoscience and Glycotechnology, School of Medicine and Pharmacy, Ocean University of China, Qingdao 266003, China. and Laboratory for Marine Drugs and Bioproducts, Pilot National Laboratory for Marine Science and Technology (Qingdao), Qingdao 266237, China
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Tseng P, Sie Z, Liu M, Lin H, Yang W, Lin T, Hsieh H, Hung S, Cheng C, Wang H, Chang H, Yuh C. Identification of Two Novel Small Compounds that Inhibit Liver Cancer Formation in Zebrafish and Analysis of Their Conjugation to Nanodiamonds to Further Reduce Toxicity. ADVANCED THERAPEUTICS 2019. [DOI: 10.1002/adtp.201900105] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Affiliation(s)
- Po‐Han Tseng
- Institute of Molecular and Genomic Medicine National Health Research Institutes Zhunan Miaoli 35053 Taiwan
- Institute of Biotechnology National Tsing Hua University Hsinchu 30010 Taiwan
| | - Zong‐Lin Sie
- Institute of Molecular and Genomic Medicine National Health Research Institutes Zhunan Miaoli 35053 Taiwan
- Institute of Biotechnology National Tsing Hua University Hsinchu 30010 Taiwan
| | - Meng‐Chieh Liu
- Institute of Molecular and Genomic Medicine National Health Research Institutes Zhunan Miaoli 35053 Taiwan
- Institute of Biotechnology National Tsing Hua University Hsinchu 30010 Taiwan
| | - Han‐Syuan Lin
- Institute of Molecular and Genomic Medicine National Health Research Institutes Zhunan Miaoli 35053 Taiwan
- Institute of Biotechnology National Tsing Hua University Hsinchu 30010 Taiwan
| | - Wan‐Yu Yang
- Institute of Molecular and Genomic Medicine National Health Research Institutes Zhunan Miaoli 35053 Taiwan
| | - Ting‐Yu Lin
- Institute of Molecular and Genomic Medicine National Health Research Institutes Zhunan Miaoli 35053 Taiwan
| | - Hsing‐Pang Hsieh
- Institute of Biotechnology and Pharmaceutical Research National Health Research Institutes Zhunan Miaoli 35053 Taiwan
| | - Shih‐Che Hung
- Institute of Medical Sciences Tzu‐Chi University Hualien 97004 Taiwan
- Department of Molecular Biology and Human Genetics Tzu‐Chi University Hualien 97004 Taiwan
| | - Chia‐Liang Cheng
- Department of Physics National Dong Hwa University Hualien 97447 Taiwan
| | - Horng‐Dar Wang
- Institute of Biotechnology National Tsing Hua University Hsinchu 30010 Taiwan
| | - Hsin‐Hou Chang
- Institute of Medical Sciences Tzu‐Chi University Hualien 97004 Taiwan
- Department of Molecular Biology and Human Genetics Tzu‐Chi University Hualien 97004 Taiwan
| | - Chiou‐Hwa Yuh
- Institute of Molecular and Genomic Medicine National Health Research Institutes Zhunan Miaoli 35053 Taiwan
- Department of Biological Science and Technology National Chiao Tung University Hsinchu 30010 Taiwan
- Institute of Bioinformatics and Structural Biology National Tsing‐Hua University Hsinchu 30071 Taiwan
- Ph.D. Program in Environmental and Occupational Medicine Kaohsiung Medical University Kaohsiung 80708 Taiwan
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