Urchin-Shaped Metal Organic/Hydrogen-Bonded Framework Nanocomposite as a Multifunctional Nanoreactor for Catalysis-Enhanced Synergetic Therapy

Ultrasound (US)-induced sonodynamic therapy (SDT) is an efficient and precise method against tumor, and the integration of multiple cancer therapies has been proved as a promising strategy for better therapeutic effects. Herein, for the first time, a multifunctional nanoreactor has been fabricated by integrating Fe-MIL-88B-NH2, PFC-1, and glucose oxidase (GO(x)) to form urchin-like Fe-MIL-88B-NH2 @PFC-1-GO(x)(MPG) nanoparticles as Fenton's reagent, a sonosensitizer, and a tumor microenvironment (TME) modulator. In detail, MPG can generate (OH)-O-center dot for chemodynamic therapy (CDT) and deplete glutathione (GSH) to alleviate the antioxidant ability of cancer cells. Moreover, catalase (CAT)-like MPG can react with H2O2 to generate O-2 for relieving hypoxia in TME, enhancing GO(x) -catalyzed glucose oxidation to produce H2O2 and gluconic acid. Then, the regenerated H2O2 can promote the Fenton reaction to achieve GO(x) catalysis-enhanced CDT. Owing to its large pi-electron conjugated system, MPG also serves as an ideal sonosensitizer, realizing a burst generation of O-1(2) under US irradiation for efficient SDT. Therefor; the tumor treatment will be notably enhanced by MPG-based synergetic CDT/SDT/starvation therapy via a series of cascade reactions. Overall, this work develops a versatile nanoreactor with improved tumor treatment effectiveness and broadens the application prospects of porous materials in the field of biomedical research.

Automated summary

Ultrasound-induced sonodynamic therapy (SDT) combined with multifunctional nanoreactor MPG showed enhanced tumor treatment effectiveness through a series of cascade reactions, including chemodynamic therapy (CDT), relieving hypoxia in TME, GO(x) catalysis-enhanced CDT, and efficient SDT. This work broadens the application prospects of porous materials in biomedical research.