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 MDR arises from overexpression P-glycoprotein (P-gp), which actively enhances drug efflux and limits effectiveness chemotherapeutic agents. Results In this study, we fabricated “combo” nanoagent equipping with triple synergistic strategies for enhancing antitumor against cells. Tumor homing-penetrating peptide endows nanosystem targeting penetrating capabilities first stage tumor internalization. abundant amine groups polyethylenimine (PEI)-modified nanoparticles then trigger proton sponge effect to promote endo/lysosomal escape, intracellular accumulation retention anticancer drugs. Furthermore, copper tetrakis(4-carboxyphenyl)porphyrin (CuTCPP) encapsulated nanosystem, effectively scavenges endogenous glutathione (GSH) reduce detoxification mediated by GSH sensitize cells drugs, while simultaneously serving as photoacoustic imaging (PAI) contrast agent image visualization. Moreover, also verify these versatile combination PD-1/PD-L1 blockade therapy can not only activate immunological responses but inhibit P-gp expression obliterate primary metastatic tumors. Conclusion This work shows significant enhancement therapeutic syngeneic tumors using multiple reversing compared an equivalent dose free paclitaxel. Graphic