Cold Nanozyme for Precise Enzymatic Antitumor Immunity.

Abstract

Precise catalysis is pursued for the biomedical applications of artificial enzymes. It is feasible to precisely control the catalysis of artificial enzymes via tunning the temperature-dependent enzymatic kinetics. The safety window of cold temperatures (4-37 °C) for the human body is much wider than that of thermal temperatures (37-42 °C). Although the development of cold-activated artificial enzymes is promising, there is currently a lack of suitable candidates. Herein, a cold-activated artificial enzyme is presented with Bi₂Fe₄O₉ nanosheets (NSs) as a paradigm. The as-obtained Bi₂Fe₄O₉ NSs possess glutathione oxidase (GSHOx)-like activity under cold temperature due to their pyroelectricity. Bi₂Fe₄O₉ NSs trigger the cold-enzymatic death of tumor cells via apoptosis and ferroptosis, and minimize the off-target toxicity to normal tissues. Moreover, an interventional device is fabricated to intelligently and remotely control the enzymatic activity of Bi₂Fe₄O₉ NSs on a smartphone. With Bi₂Fe₄O₉ NSs as an <i>in situ</i> vaccine, systemic antitumor immunity is successfully activated to suppress tumor metastasis and relapse. Moreover, blood biochemistry analysis and histological examination indicate the high biosafety of Bi₂Fe₄O₉ NSs for <i>in vivo</i> applications. This cold nanozyme provides a strategy for cancer vaccines, which can benefit the precise control over catalytic nanomedicines.