Amplified antitumor efficacy by a targeted drug retention and chemosensitization strategy-based "combo" nanoagent together with PD-L1 blockade in reversing multidrug resistance.

ABSTRACT:

Background

Recent studies have demonstrated that multidrug resistance (MDR) is a critical factor in the low efficacy of cancer chemotherapy. The main mechanism of MDR arises from the overexpression of P-glycoprotein (P-gp), which actively enhances drug efflux and limits the effectiveness of chemotherapeutic agents.

Results

In this study, we fabricated a "combo" nanoagent equipping with triple synergistic strategies for enhancing antitumor efficacy against MDR cells. Tumor homing-penetrating peptide endows the nanosystem with targeting and penetrating capabilities in the first stage of tumor internalization. The abundant amine groups of polyethylenimine (PEI)-modified nanoparticles then trigger a proton sponge effect to promote endo/lysosomal escape, which enhances the intrac

SUBMITTER: Jiang W 

PROVIDER: S-EPMC8256488 | biostudies-literature | 2021 Jul

REPOSITORIES: biostudies-literature