Fenton-like reaction and glutathione depletion by chiral manganese dioxide nanoparticles for enhanced chemodynamic therapy and chemotherapy

Chirality-based nanomaterials, especially semiconductors nanoparticles (NPs), are the emerging research in biomedicine field. Herein, chiral manganese dioxide (L/D-MnO2) NPs were synthesized by using threonine molecules as chiral ligands. Then cisplatin loaded L/D-MnO2 (L/D-MnO2@Pt) NPs were successfully constructed based on the high specific surface area of L/D-MnO2 NPs. L/D-MnO2@Pt NPs could be specifically internalized by tumor cells and efficiently deplete the glutathione (GSH) through redox reaction to release Mn2+ and Pt. The released Mn2+ exhibited strong chemodynamic effect through Fenton-like reaction. The depletion of GSH further improved the chemodynamic therapy (CDT) efficiency. The combination of the CDT of Mn2+ with the chemotherapy of Pt considerably enhanced the tumor therapy efficiency. It was particularly noteworthy that L/D-MnO2@Pt NPs showed chirality-based different internalization by tumor cells and further led to different tumor cell ablation effects, in which D-MnO2@Pt NPs exhibited stronger therapeutic efficiency than L-MnO2@Pt NPs. These findings provided deep insights for novel biomedical applications of chirality-based semiconductors NPs.