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- W3201110659 abstract "Ferroptosis is a new form of regulated cell death with significant therapeutic prospect, but its application against drug-resistant tumor cells is challenging due to their ability to effuse antitumor agents via p-glycoprotein (P-gp) and anti-lipid peroxidation alkaline intracellular environment. Herein, an amorphous calcium phosphate (ACP)-based nanoplatform is reported for the targeted combinational ferroptosis/apoptosis therapy of drug resistant tumor cells by blocking the MCT4-mediated efflux of lactic acid (LA). The nanoplatform is fabricated through the biomineralization of doxorubicin-Fe2+ (DOX-Fe2+) complex and MCT4-inhibiting siRNAs (siMCT4) and can release them to the tumor cytoplasm after the hydrolysis of ACP and dissociation of DOX-Fe2+ in the acidic lysosomes. siMCT4 can inhibit MCT4 expression and force the glycolysis-generated lactic acid (LA) to remain in cytoplasm for rapid acidification. The nanoplatform-induced remodeling of the tumor intracellular environment can not only interrupt the ATP supply required for P-gp-dependent DOX effusion to enhance H2O2 production, but also increase the overall catalytic efficiency of Fe2+ for the initiation and propagation of lipid peroxidation. These features could act in concert to enhance the efficacy of the combinational ferroptosis/chemotherapy and prolong the survival of tumor-bearing mice. This study may provide new avenues for the treatment of multidrug-resistant tumors." @default.
- W3201110659 created "2021-09-27" @default.
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- W3201110659 date "2021-09-23" @default.
- W3201110659 modified "2023-10-15" @default.
- W3201110659 title "Activatable Biomineralized Nanoplatform Remodels the Intracellular Environment of Multidrug‐Resistant Tumors for Enhanced Ferroptosis/Apoptosis Therapy" @default.
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- W3201110659 doi "https://doi.org/10.1002/smll.202102269" @default.
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