Phosphate-Degradable Nanoparticles Based on Metal–Organic Frameworks for Chemo-Starvation-Chemodynamic Synergistic Antitumor Therapy

过氧化氢 阿霉素 激进的 纳米医学 葡萄糖氧化酶 肿瘤微环境 材料科学 磷酸盐 纳米颗粒 羟基自由基 化学 癌症研究 生物物理学 催化作用 化疗 组合化学 活性氧 生物化学 纳米技术 肿瘤细胞 生物 遗传学
作者
Hui Peng,Yating Qin,Yusheng Feng,Xiwen He,Wen‐You Li,Yukui Zhang
出处
期刊:ACS Applied Materials & Interfaces [American Chemical Society]
卷期号:13 (31): 37713-37723 被引量:31
标识
DOI:10.1021/acsami.1c10816
摘要

Chemodynamic therapy (CDT) was regarded as a promising approach for tumor treatment. However, owing to the insufficient amount of endogenous hydrogen peroxide (H2O2) in tumor cells, the efficacy of CDT was limited. In this study, we designed phosphate-responsive nanoparticles (denoted as MGDFT NPs) based on metal–organic frameworks, which were simultaneously loaded with drug doxorubicin (DOX) and glucose oxidases (GOx). The decorated GOx could act as a catalytic nanomedicine for the response to the abundant glucose in the tumor microenvironment, generating a great deal of H2O2, which would enhance the Fenton reaction and produce toxic hydroxyl radicals (·OH). Meanwhile, the growth of tumors would also be inhibited by overconsuming the intratumoral glucose, which was the "fuel" for cell proliferation. When the nanoparticles entered into tumor cells, a high concentration of phosphate induced structure collapse, releasing the loaded DOX for chemotherapy. Furthermore, the decoration of target agents endowed the nanoparticles with favorable target ability to specific tumor cells and mitochondria. Consequently, the designed MGDFT NPs displayed desirable synergistic therapeutic effects via combining chemotherapy, starvation therapy, and enhanced Fenton reaction, facilitating the development of multimodal precise antitumor therapy.
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