Proficient photothermal-enhanced cascade catalytic nanoplatform for multi-responsive release and synergistic tumor therapy

The chemotherapy effect is generally affected by the premature release of nanoplatform and multi-drug resistance. In light of the advantages of photothermal therapy (PTT) and cascade catalytic therapy, we developed a multi-sensitive drug delivery system (MHC-Au-P) by grafting the gold NPs onto the opening of mesoporous hollow carbon nanoparticles (MHC) using gold sulfur bonds. MHC had excellent photothermal conversion efficiency and GSH consumption function, serving as a carrier for highly loading doxorubicin (DOX). The gold NPs were used due to their diverse functions, including smart switches to block the release of harmful substances, PTT agents to enhance the thermogenic effect of MHC, and nanozymes with GOx-like activity. When physical conditions are normal, gold-sulfur bond, which serves as the link between MHC carrier and Au-NPs, was stable, but the stability will decrease when glutathione (GSH) concentration in tumor cytoplasm was high. The DOX loaded D@MHC-Au-P can be rapidly decomposed into DOX@MHC and gold NPs at high GSH concentration after reaching the tumor microenvironment. The separated Au-NPs was capable of catalyzing the oxidation of glucose to H 2 O 2 and glucuronic acid, providing raw materials and optimizing conditions for the POD-like enzyme catalysis of MHC. Under near-infrared irradiation, the release rate of drugs was further accelerated, GSH consumption rate, the catalytic rate of Au-NPs and MHC were further improved. The synergistic effect of D@MHC-Au-P for PTT-enhanced cascade catalytic therapy and chemotherapy was realized in vivo and in vitro with a combination index of 0.62. Therefore, D@MHC-Au-P can be used as a smart nanocarrier for photothermal-enhanced synergistic cascade catalysis and chemotherapy.