Tumor Microenvironment-Adaptive Nanoplatform Synergistically Enhances Cascaded Chemodynamic Therapy

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 H₂O₂, pH value, the hypoxic environment of tumors, and it has suboptimal tumor-targeting ability. In this study, tumor cell membrane-camouflaged mesoporous Fe₃O₄ nanoparticles loaded with perfluoropentane (PFP) and glucose oxidase (GOx) are used as a tumor microenvironment-adaptive nanoplatform (M-mFeP@O₂-G), which synergistically enhances the antitumor effect of CDT. Mesoporous Fe₃O₄ 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 H₂O₂ for subsequent ·OH generation. Moreover, PFP, which can carry O₂, relieves hypoxia in tumor cells and provides O₂ 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@O₂-G, with a desirable tumor-inhibition rate (90.50%), which indicates the great potential of this platform for clinical treating cancer.