Glutathione and H2O2 consumption promoted photodynamic and chemotherapy based on biodegradable MnO2–Pt@Au25 nanosheets

Photodynamic therapy (PDT) has become a significant anticancer method by making full use of reactive oxygen species (ROS) to kill cancer cells. However, high concentration of reductive glutathione (GSH) in tumor site is an enemy, which can decrease the PDT efficacy due to ROS consumption property of reductive GSH. To overcome the problem, here we design an innovative nanoplatform, which could integrate PDT, chemotherapy and magnetic resonance imaging (MRI) in one nanosystem. In this platform, MnO2 nanosheets were employed as the carrier by conjugating photosensitizer (Au25 nanoclusters) with platinum(IV) (Pt(IV)) prodrugs for synergistic PDT and chemotherapy. Interestingly, GSH can reduce MnO2 nanosheets and Pt(IV) prodrugs simultaneously. Consequently, the concentration of intercellular GSH has been greatly decreased. More importantly, Mn2+ reduced from MnO2 nanosheets remarkably improves both T1– and T2–weighted MRI owing to high level of GSH and H2O2 in acidic tumor microenvironment, and Pt(II) reduced from Pt(IV) gives rise to high chemotoxicity to cancer cells. Combined with high PDT efficiency by consuming large amount of intercellular GSH, this nanoplatform has successfully achieved the MRI guided synergistic therapy, which is promising for potential clinic applications in cancer therapy.