Nanoporous Silica Nanoparticles Coloaded with Cisplatin Prodrug and L-Buthionine Sulfoximine for Cancer Therapy

Intracellular glutathione (GSH) is critical for cisplatin-resistant cancers by maintaining the redox balance. Amplifying the intracellular oxidative stress by disrupting the redox balance is an effective method for the treatment of cancers. Therefore, we design a mesoporous silica (MS) nanosystem coated by hyaluronic acid (HA) to codeliver L-buthionine sulfoximine (BSO) and cisplatin prodrug (DSCP) (defined as Pt/BSO-MS-HA). The intracellular GSH could react with DSCP in Pt/BSO-MS-HA, which could release free cisplatin for chemotherapy, and the BSO block the synthesis of GSH, leading to GSH depletion and disrupting the redox balance. Moreover, HA provides homotypic binding capacities and superior immune evasion, which significantly enhance the cell uptake of Pt/BSO-MS-HA and tumor accumulation. In in vivo studies, Pt/BSO-MS-HA could efficiently inhibit tumor growth and showed no obvious side effects. Our study provides an effective strategy to develop biocompatible drug delivery nanosystem by disrupting the redox balance in cancer cells, which significantly increase the therapeutic efficiency of cancer chemotherapy.

Automated summary

Researchers designed a nano system that disrupts the redox balance to increase intracellular oxidative stress and improve the treatment of cisplatin-resistant cancer cells. This nano system can co-deliver L-buthionine sulfoximine and cisplatin prodrug, releasing free cisplatin for chemotherapy and depleting intracellular glutathione to disrupt the redox balance. Moreover, hyaluronic acid enhances the cell uptake and tumor accumulation of the nano system. In vivo studies showed that this nano system efficiently inhibits tumor growth without obvious side effects.