Construction a starving therapy induced photothermal enhanced cascade nanoreactor for imaging guided catalytic synergistic therapy of tumor

Abstract

Multienzyme cascade reaction has shown great potential in tumor therapy and photothermal was usually introduced to nanozyme to improve the catalytic efficiency which is limited by tumor microenvironment. However, it is difficult to determine the optimal treatment window in photothermal enhanced catalytic therapy. In order to solve the problem, a trackable-imaging multifunctional cascade reactor was designed with glucose oxidase (GOx) loaded bimetallic Fe/Cu-MOF-199 as core and polydopamine (PDA) as shell, with the pH/GSH targeting of the shell PDA, Fe/Cu-MOF-199/GOx@PDA can be enriched in tumor cells. With the release of GOx from the core Fe/Cu-MOF-199, the glucose in tumor can be catalyzed to supply H2O2, reduce heat resistance, and with the self-cyclic valence alteration of Fe3+/Fe2+ and Cu2+/Cu+, GSH can be constantly consumed, greatly reducing the anti-oxidation defense effect of tumor. Through the activities of catalase and peroxidase of Fe/Cu-MOF-199, O2 and hydroxyl radicals (•OH) are generated to kill cancer cells and compensate for O2 consumed in glucose catalytic reaction, respectively. Furthermore, under MRI guiding, near-infrared light excitation is performed at the optimal concentration of Fe/Cu-MOF-199/GOx@PDA in the tumor. Promoting the multienzyme activity in TME to the greatest extent. Cytotoxicity proved the selectivity, and in vivo experiments confirmed that the catalytic synergistic treatment of multienzyme cascade reaction and photothermal therapy was satisfactory. The study provides new promising ideas for designing multifunctional cascade nanoreactor for efficient cancer treatment.