Cathepsin B-responsive nanodrug delivery systems for precise diagnosis and targeted therapy of malignant tumors |
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| Institution: | 1. College of Pharmaceutical Sciences, Southwest University, Chongqing 400716, China;2. Huaxi MR Research Center (HMRRC), Department of Radiology, Functional and molecular imaging Key Laboratory of Sichuan Province, West China Hospital, Sichuan University, Chengdu 610041, China;3. Department of Chemistry, Key Laboratory of Functional Inorganic Material Chemistry of Anhui Province, Anhui University, Hefei 230039, China;4. Amgen Bioprocessing Centre, Keck Graduate Institute, Claremont, CA 91711, United States;1. The Institute for Drug Research, School of Pharmacy, Faculty of Medicine, Hebrew University, Jerusalem, Israel;2. Department of Molecular Microbiology and Biotechnology, George S. Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv, Israel;3. Department of Oral Biology, The Goldschleger School of Dental Medicine, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel;4. Department of Biochemistry and Molecular Biology, J. Stefan Institute, Ljubljana, Slovenia;5. Faculty of Chemistry and Chemical Technology, University of Ljubljana, Slovenia;6. Centre of Excellence for Integrated Approaches in Chemistry and Biology of Proteins, Jamova cesta 39, SI-1000 Ljubljana, Slovenia;7. Department of Materials Science and Engineering, Iby and Aladar Fleischman Faculty of Engineering, Tel Aviv University, Tel Aviv, Israel;1. Tianjin Key Laboratory on Technologies Enabling Development of Clinical Therapeutics and Diagnostics (Theranostics), School of Pharmacy, Tianjin Medical University, Tianjin 300070, PR China;2. Collaborative Innovation Center of Chemical Science and Chemical Engineering, School of Chemical Engineering and Technology, Tianjin University, Tianjin 300072, PR China;3. College of Pharmacy and Research Institute of Pharmaceutical Sciences, Gyeongsang National University, Jinjudaero, Jinju, Gyeongnam 660-751, South Korea;4. Department of Pharmaceutical Sciences, College of Pharmacy, University of Michigan, Ann Arbor 48109-1065, USA;5. Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology and College of Medicine or College of Pharmacy, Seoul National University, Seoul, South Korea |
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| Abstract: | The tumor microenvironment (TME) significantly influences cancer evolution and therapeutic efficacy. Targeting biofunctional molecules to the TME has long been appreciated as a means of raising local drug concentrations and reducing systemic toxicities. The booming nanotechnology field has realized the importance of cathepsin B to derive a variety of intelligent enzyme-responsive nanosized drug delivery systems (nanoDDS) to improve treatment responses and clinical outcomes. In this tutorial review, after introducing the molecular structure and physiological/pathological functions of cathepsin B, the outstanding achievements of cathepsin B-responsive nanoplatforms in the precise diagnosis, targeted therapy, and synergistic theranostics of malignant tumors are systematically described. Finally, the challenges of enzyme-substrate incompatibility, low diagnostic sensitivity, mass production and biocompatibility of multifunctional nanoDDS are considered in order to successfully promote them to clinical applications |
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| Keywords: | Tumor microenvironment Cathepsin B Theranostics Precise diagnosis Targeted therapy |
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