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Dynamic covalent chemistry-regulated stimuli-activatable drug delivery systems for improved cancer therapy
Institution:1. State Key Laboratory of Drug Research & Center of Pharmaceutics, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China;2. Key Laboratory of Smart Drug Delivery (Ministry of Education), State Key Laboratory of Medical Neurobiology, Department of Pharmaceutics, School of Pharmacy, Fudan University, Shanghai 201203, China;3. University of Chinese Academy of Sciences, Beijing 100049, China;1. State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics & Center for Molecular Imaging and Translational Medicine, School of Public Health, Xiamen University, Xiamen 361102, China;2. Department of Magnetic Resonance Imaging, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China;1. State Key Laboratory of Drug Research & Center of Pharmaceutics, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China;2. Department of Medical Ultrasound, Shanghai Tenth People’s Hospital, Ultrasound Research and Education Institute, Tongji University School of Medicine, Tongji University Cancer Center, Shanghai 200072, China;3. Peking University Shenzhen Institute, Shenzhen 518055, China;4. State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macau 999078, China;5. State Key Laboratory of Polymer Physics and Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, China
Abstract:Drug delivery systems(DDSs) are of paramount importance to deliver drugs at the intended targets,e.g.,tumor cells or tissue by prolonging blood circulation and optimizing the pharmaceutical profiles.However,the therapeutic efficacy of DDSs is severely impaired by insufficient or non-specific drug release.Dynamic chemical bonds having stimuli-liable prope rties are the refore introduced into DDSs for regulating the drug release kinetics.This review summarizes the recent advances of dynamic covalent chemistry in the DDSs for improving cancer therapy.The review discusses the constitutions of the major classes of dynamic covalent bonds,and the respective applications in the tumor-targe ted DDSs which are based on the different responsive mechanisms,including acid-activatable and reduction-activatable.Furthermore,the review also discusses combination strategies of dual dynamic covale nt bonds which can response to the complex tumor microenvironment much more accurately,and then summarizes and analyzes the prospects for the application of dynamic covalent chemistry in DDSs.
Keywords:Cancer therapy  Drug delivery systems  Dynamic covalent chemistry  Acid-responsive  Reduction-responsive
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