Tumor microenvironment-responsive hyaluronic acid-oxaliplatin nanoparticles enhanced tumor cell elimination

Oxaliplatin (OXA) is widely utilized in clinical cancer treatment, however its effectiveness is hindered by drug resistance and severe side effects resulting from non-targeted delivery and lack of response to the tumor environment. In this research, thiol modified OXA and oligo hyaluronic acid (oHA) were used to developed a redox-responsive OXA-SS-oHA nanoparticle delivery system. The nanoparticles could release oxaliplatin prodrug OXA-SH through the cleavage of disulfide bonds in response of the abundant GSH in the tumor environment. OXA-SS-oHA nanoparticles were stable in aqueous solution for 7 days, and in vitro release experiments showed that the cumulative release of OXA in the absence of GSH was 21%, while in the presence of 10 mM concentration of GSH, the cumulative release was 47%. Additionally, OXA-SS-oHA demonstrated greater efficacy in inducing cell death in GSH-positive cells (MKN45) when compared to GSH-negative cells (L929). This study provides a novel strategy for the construction of GSH-stimulated responsive targeted drug delivery systems for cancer therapy.