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

Abstract 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.