Tumor acidity activated triphenylphosphonium-based mitochondrial targeting nanocarriers for overcoming drug resistance of cancer therapy.

ABSTRACT: The drug resistance in cancer treatment with DOX is mainly related to the overexpression of drug efflux proteins, residing in the plasma and nuclear membranes. Delivering DOX into the mitochondria, lacking drug efflux proteins, is an interesting method to overcome DOX resistance. To solve the problem of positively charged triphenylphosphonium (TPP) for mitochondrial targeting in vivo, a charge reversal strategy was developed. Methods: An acidity triggered cleavable polyanion PEI-DMMA (PD) was coated on the surface of positively charged lipid-polymer hybrid nanoparticle (DOX-PLGA/CPT) to form DOX-PLGA/CPT/PD via electrostatic interaction. The mitochondrial localization and anticancer efficacy of DOX-PLGA/CPT/PD was evaluated both in vitro and in vivo. R

SUBMITTER: Yu H 

PROVIDER: S-EPMC6815947 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature