Codelivery of SH-aspirin and curcumin by mPEG-PLGA nanoparticles enhanced antitumor activity by inducing mitochondrial apoptosis

Abstract

Lin Zhou,1,2,* Xingmei Duan,1,2,* Shi Zeng,1 Ke Men,1 Xueyan Zhang,1 Li Yang,1 Xiang Li1 1State Key Laboratory of Biotherapy, Cancer Center and Department of Urology, West China Hospital, Sichuan University, Chengdu, People’s Republic of China; 2Sichuan Food and Drug Safety Monitoring and Review of Certification, Adverse Reaction Monitoring Center, Drug Abuse Monitoring Center, Chengdu, People’s Republic of China *These authors contributed equally to this work Abstract: Natural product curcumin (Cur) and H2S-releasing prodrug SH-aspirin (SH-ASA) are potential anticancer agents with diverse mechanisms, but their clinical application prospects are restricted by hydrophobicity and limited efficiency. In this work, we coencapsulated SH-ASA and Cur into methoxy poly(ethylene glycol)-poly (lactide-coglycolide) (mPEG-PLGA) nanoparticles through a modified oil-in-water single-emulsion solvent evaporation process. The prepared SH-ASA/Cur-coloaded mPEG-PLGA nanoparticles had a mean particle size of 122.3±6.8 nm and were monodispersed (polydispersity index =0.179±0.016) in water, with high drug-loading capacity and stability. Intriguingly, by treating with SH-ASA/Cur-coloaded mPEG-PLGA nanoparticles, obvious synergistic anticancer effects on ES-2 and SKOV3 human ovarian carcinoma cells were observed in vitro, and activation of the mitochondrial apoptosis pathway was indicated. Our results demonstrated that SH-ASA/Cur-coloaded mPEG-PLGA nanoparticles could have potential clinical advantages for the treatment of ovarian cancer. Keywords: drug delivery, cancer therapy, ovarian cancer, synergistic effect