A Glucose Metabolic Intervention Nanoplatform for Enhanced Chemodynamic Therapy and Sensitized Photothermal Therapy of Hepatocellular Carcinoma

Traditional treatments for hepatocellular carcinoma (HCC)stilllack effectiveness. Recently, the combined mode of chemodynamic therapy(CDT) and photothermal therapy (PTT) has shown great potential againstHCC. However, insufficient Fenton reaction rates and hyperthermia-inducedheat shock responses greatly impair their efficiency, hindering theirfurther clinical application. Here, we constructed a cascade-amplifiedPTT/CDTnanoplatform by coating an IR780-embedded red blood cell membraneon glucose oxidase (GOx)-loaded Fe3O4 nanoparticlesfor effective HCC treatment. On the one hand, the nanoplatform interferedwith glucose metabolism through the action of GOx to reduce the synthesisof ATP, which reduced the expression of heat shock proteins, therebysensitizing the IR780-mediated PTT. On the other hand, hydrogen peroxidegenerated during GOx catalysis and the thermal effect of PTT acceleratedthe Fe3O4-mediated Fenton reaction, realizingenhanced CDT. Consequently, the sensitized PTT and enhanced CDT forHCC management could be simultaneously achieved by interfering withglucose metabolism, providing an alternative strategy for the effectivetreatment of tumors.