Molecularly targeted co-delivery of a histone deacetylase inhibitor and paclitaxel by lipid-protein hybrid nanoparticles for synergistic combinational chemotherapy

Abstract

In this study, a transferrin-anchored albumin nanoplatform with PEGylated lipid bilayers (Tf-L-APVN) was developed for the targeted co-delivery of paclitaxel and vorinostat in solid tumors. Tf-L-APVN exhibited a sequential and controlled release profile of paclitaxel and vorinostat, with an accelerated release pattern at acidic pH. At cellular levels, Tf-L-APVN significantly enhanced the synergistic effects of paclitaxel and vorinostat on the proliferation of MCF-7, MDA-MB-231, and HepG2 cancer cells. Vorinostat could significantly enhance the cytotoxic potential of paclitaxel, induce marked cell apoptosis, alter cell cycle patterns, and inhibit the migratory capacity of cancer cells. In addition, Tf-L-APVN showed prolonged circulation in the blood and maintained an effective ratio of 1:1 (for paclitaxel and vorinostat) throughout the study period. In HepG2 tumor-bearing mice, Tf-L-APVN displayed excellent antitumor efficacy and the combination of paclitaxel and vorinostat significantly inhibited the tumor growth. Taken together, dual drug-loaded Tf receptor-targeted nanomedicine holds great potential in chemotherapy of solid tumors.