Degradable Tumor-Responsive Iron-Doped Phosphate-Based Glass Nanozyme for HO Self-Supplying Cancer Therapy.

Tumor microenvironment (TME)-responsive chemodynamic therapy (CDT) mediated by nanozymes has been extensively studied both experimentally and theoretically, but the low catalytic efficiency due to insufficient HO in the TME and the poor biodegradability of the nanozymes are still main challenges for clinical translation of nanozymes. Herein, we designed a HO self-supplying nanozyme bearing glucose oxidase (GOX) and polyethyleneimine based on a degradable iron-doped phosphate-based glass (FePBG) nanomimic (FePBG@GOX), which can convert endogenous glucose into toxic hydroxyl radicals. The GOX loaded on the nanozyme can effectively consume glucose in tumor cells to produce a large amount of HO to make up for the lack of HO in the TME. Thereafter, enormous hydroxyl radicals, based on a Fenton reaction of FePBG without any exogenous HO, are generated to induce severe apoptosis of tumor cells. The nanozyme exhibits enhanced in vitro cytotoxicity in a high-glucose medium than in a low-glucose medium, illustrating sufficient generation of HO by GOX. The excellent in vivo antitumor efficacy is manifested by a high tumor growth inhibition ratio of 94.65% in model mice. Excellent intrinsic biodegradability owing to its phosphate-based glass nature is a remarkable advantage of the prepared FePBG nanozyme over most other reported nanozymes. Big concerns about side effects caused by long-time residence in living organisms are eliminated since it degrades not only in an acid medium but also in a neutral physiological environment. Therefore, this novel strategy of the TME-responsive HO self-supplying nanozyme based on an endogenous cascade catalytic reaction opens up an avenue for designing degradable nanozymes in CDT.