pH-activated metal–organic layer nanozyme for ferroptosis tumor therapy

Nanozymes have made great achievements in the research of tumor therapy. However, due to the complex tumor microenvironment, the catalytic activity and biosafety of nanozymes are limited. High catalytic efficiency is a relentless pursuit for the preparation of high-performance nanozymes. Dimensional reduction from 3D nanoscale metal–organic frameworks (nMOFs) to 2D nanoscale metal–organic layers (nMOLs) increases the encounters frequency of nanozymes and substrate, which facilitates the diffusion of reactive oxygen species (ROS) from nMOLs, thus significantly improving the effectiveness of chemodynamic therapy. In this study, He@Ce-BTC nMOF and He@Ce-BTB nMOL based on Ce₆ SBUs were synthesized by solvothermal reaction. Compared with the 3D nMOFs, the 2D nanozymes He@Ce-BTB nMOL possessed enhanced ROS catalytic efficiency, were able to be activated by the tumor acidic microenvironment with the polymerase mimetic activities (CAT, POD, GSH-OXD) that enhances the lipid peroxidation process and accelerates the process of ferroptosis thereby killing tumor cells. In addition, He@Ce-BTB does not affect normal tissue cells, thus avoiding diffusion-induced side effects. He@Ce-BTB has shown excellent therapeutic effects in vitro and in vivo, which indicates its potential for clinical application, and is expected to become a new generation of drugs for the treatment of tumors.