Redox-responsive micelles integrating catalytic nanomedicine and selective chemotherapy for effective tumor treatment |
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Institution: | 1. School of Chemical Engineering and Technology, Shaanxi Key Laboratory of Energy Chemical Process Intensification, Institute of Polymer Science in Chemical Engineering, Xi’an Jiao Tong University, Xi’an 710049, China;2. Department of Prosthodontics, Peking University School and Hospital of Stomatology, National Engineering Laboratory for Digital and Material Technology of Stomatology, Beijing Key Laboratory of Digital Stomatology, Beijing 100081, China;3. Pharmaceutical College, Guangxi Medical University, Nanning 530021, China |
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Abstract: | Chemotherapy is one of the most conventional modalities for cancer therapy. However, the high multidrug resistance of tumor cells still limited the clinical application of current chemotherapy. Considering the ability of nitric oxide (NO) to modulate potent P-glycoprotein to inhibit multi-drug resistance, a synergistic methodology combining chemotherapy and sustained NO generation is an ideal way to further promote the chemotherapy. Herein, a multi-functional micelle with tumor-selective chemotherapy driven by redox-triggered doxorubicin (DOX) release and drug resistance inhibition based on intracellular NO generation was fabricated for effective tumor treatment. The micelle consists of DOX as core, arginine/glucose oxidase (Arg/GOx) as shell and redox-responsive disulfide bond as a linker, which is denoted as micelle-DOX-Arg-GOx. The Arg serves as the biological precursor of nitric oxide for inhibition of multi-drug resistance to promote chemotherapy and GOx catalyzes glucose to produce hydrogen peroxide (H2O2) for increasing the generation of NO. Moreover, the glucose supply could be simultaneously blocked by the catalytic process, which further enhanced therapeutic efficiency. This micelle requests a tumor-specific microenvironment (a considerable amount of GSH) to perform synergistic therapeutics including chemotherapy, starvation therapy (catalytic medicine), and gas therapy for tumor treatment, which resulted in significant cytotoxicity to tumor tissue. |
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Keywords: | Chemotherapy Gas therapy Starvation therapy Carrier-free Tumor treatment |
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