One-Pot\nSynthesis of a pH-Sensitive MOF Integrated\nwith Glucose Oxidase for Amplified Tumor Photodynamic/Photothermal\nTherapy

Photothermal\ntherapy (PTT) and photodynamic therapy (PDT) provide\ntargeted approaches to cancer treatment, but each therapy has inherent\nlimitations such as insufficient tissue penetration, uneven heat distribution,\nextreme hypoxia, and overexpressed HSP90 in tumor cells. To address\nthese issues, herein, by encapsulating the IR780 dye and glucose oxidase\n(GOx) enzyme within ZIF-8 nanoparticles, we created a versatile system\ncapable of combining photodynamic and enhanced photothermal therapy.\nThe integration of the IR780 dye facilitated the generation of reactive\noxygen species and hyperthermia upon light activation, enabling dual-mode\ncancer cell ablation. Moreover, GOx catalyzes the decomposition of\nglucose into gluconic acid and hydrogen peroxide, leading to the inhibition\nof ATP production and downregulation of heat shock protein 90 (HSP90)\nexpression, sensitizing cancer cells to heat-induced cytotoxicity.\nThis synergistic combination resulted in significantly improved therapeutic\noutcomes. Both in vitro and in vivo results validated that the nanoplatform\ndemonstrated superior specificity and favorable therapeutic responses.\nOur innovative approach represents a promising strategy for overcoming\ncurrent limitations in cancer treatments and offers the potential\nfor clinical translation in the future.