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.