PLGA nanoparticle-based docetaxel/LY294002 drug delivery system enhances antitumor activities against gastric cancer

Abstract

Docetaxel (TXT) is acknowledged as one of the most important chemotherapy agents for gastric cancer (GC). PI3K/AKT signaling is frequently activated in GC, and its inhibitor LY294002 exerts potent antitumor effects. However, the hydrophobicity of TXT and the poor solubility and low bioavailability of LY294002 limit their clinical application. To overcome these shortcomings, we developed poly(lactic acid/glycolic) (PLGA) nanoparticles loaded with TXT and LY294002. PLGA facilitated the accumulation of TXT and LY294002 at the tumor sites. The in vitro functional results showed that PLGA(TXT+LY294002) exhibited controlled-release and resulted in a markedly reduced proliferative capacity and an elevated apoptosis rate. An in vivo orthotopic GC mouse model and xenograft mouse model confirmed the anticancer superiority and tumor-targeting feature of PLGA(TXT+LY294002). Histological analysis indicated that PLGA(TXT+LY294002) was biocompatible and had no toxicity to major organs. Characterized by the combined slow release of TXT and LY294002, this novel PLGA-based TXT/LY294002 drug delivery system provides controlled release and tumor targeting and is safe, shedding light on the future of targeted therapy against GC.