Glucose/Glutathione Co-triggered Tumor Hypoxia Relief and Chemodynamic Therapy to Enhance Photothermal Therapy in Bladder Cancer.

Photothermal therapy (PTT) is a potential treatment for cancer that makes use of near-infrared (NIR) laser irradiation and is expected to assist traditional anti-cancer drug therapies; however, the therapeutic efficacy of PTT is restricted by thermal resistance due to the overexpression of heat shock proteins and insufficient penetration depth of lasers. Thus, PTT needs to be combined with additional therapeutic methods to obtain the optimal therapeutic efficacy for cancer. Herein, a multifunctional therapeutic platform combining PTT with glucose-triggered chemodynamic therapy (CDT) and glutathione (GSH)-triggered hypoxia relief was developed via GOx@MBSA-PPy-MnO 2 NPs (GOx for glucose oxidase, M for Fe 3 O 4 , BSA for bovine serum albumin, and PPy for polypyrrole). GOx@MBSA-PPy-MnO 2 NPs have excellent photothermal efficiency and can release Mn 2+ , which catalyzes the transformation of H 2 O 2 into hydroxyl radicals (·OH) and O 2 via a Fenton-like reaction, effectively destroying cancer cells and relieving tumor hypoxia. Meanwhile, a high content of H 2 O 2 was produced via GOx catalysis of glucose, further enhancing the CDT efficiency. In addition, in vitro and in vivo experiments showed that the inhibition of cancer cell proliferation and effective inhibition of tumors could be caused by the combined PTT/glucose-triggered CDT effects and hypoxia relief of the GOx@MBSA-PPy-MnO 2 NPs. Overall, this work provides evidence of a synergistic therapy that remarkably improves therapeutic efficacy and significantly prolongs the lifetime of mice compared with controls.