Synergistically remodulating H⁺/Ca²⁺ gradients to induce mitochondrial depolarization for enhanced synergistic cancer therapy.

ABSTRACT: The remodulation of H⁺/Ca²⁺ gradients in the mitochondria matrix could be effective to induce mitochondria depolarization for the enhancement of cancer therapy. However, it is still challenged by H⁺ homeostasis, insufficient Ca²⁺, uncoordinated regulations, and inefficient loading/delivery strategies. Herein, a supramolecular DNA nanocomplex (Ca@DNA-MF) was prepared to synergistically remodulate H⁺/Ca²⁺ gradients for mitochondrial depolarization. Upon targeted functionalization and TME-triggered delivery, multiple reagents were released in cancer cells for synergistic three-channel mitochondrial depolarization: the gene reagent of siMCT4 blocked the LA metabolism to induce mitochondrial acidification by downregulating monoca

SUBMITTER: Wang X 

PROVIDER: S-EPMC10599464 | biostudies-literature | 2023 Oct

REPOSITORIES: biostudies-literature