Cold Nanozyme for Precise Enzymatic Antitumor Immunity

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 degrees C) for the human body is much wider than that of thermal temperatures (37-42 degrees 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 in situ 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 in vivo applications. This cold nanozyme provides a strategy for cancer vaccines, which can benefit the precise control over catalytic nanomedicines.

Automated summary

This study presents a cold-activated artificial enzyme using Bi2Fe4O9 nanosheets as a paradigm. The Bi2Fe4O9 nanosheets exhibit glutathione oxidase-like activity under cold temperature, enabling the cold-enzymatic death of tumor cells and minimizing off-target toxicity. A remotely controlled interventional device is also developed, and systemic antitumor immunity is activated using the Bi2Fe4O9 nanosheets as an in situ vaccine.