Tumor Microenvironment-Adaptive Nanoplatform Synergistically Enhances Cascaded Chemodynamic Therapy

肿瘤微环境适应性纳米平台协同增强级联化疗动力疗法

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Abstract

Chemodynamic therapy (CDT), a noninvasive strategy, has emerged as a promising alternative to conventional chemotherapy for treating tumors. However, its therapeutic effect is limited by the amount of H(2)O(2), pH value, the hypoxic environment of tumors, and it has suboptimal tumor-targeting ability. In this study, tumor cell membrane-camouflaged mesoporous Fe(3)O(4) nanoparticles loaded with perfluoropentane (PFP) and glucose oxidase (GOx) are used as a tumor microenvironment-adaptive nanoplatform (M-mFeP@O(2)-G), which synergistically enhances the antitumor effect of CDT. Mesoporous Fe(3)O(4) nanoparticles are selected as inducers for photothermal and Fenton reactions and as nanocarriers. GOx depletes glucose within tumor cells for starving the cells, while producing H(2)O(2) for subsequent ·OH generation. Moreover, PFP, which can carry O(2), relieves hypoxia in tumor cells and provides O(2) for the cascade reaction. Finally, the nanoparticles are camouflaged with osteosarcoma cell membranes, endowing the nanoparticles with homologous targeting and immune escape abilities. Both in vivo and in vitro evaluations reveal high synergistic therapeutic efficacy of M-mFeP@O(2)-G, with a desirable tumor-inhibition rate (90.50%), which indicates the great potential of this platform for clinical treating cancer.

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