An Unusual Application of Multifunctional Nanozyme Derived from COF: Augmenting Chemoimmunotherapy while Attenuating Cardiotoxicity

Abstract Enhancing therapeutic efficacy while reducing the adverse effects of drugs is crucial in cancer treatments. In this study, nitrogen‐doped carbon nanospheres are synthesized with variable enzymatic activities through the pyrolysis of a covalent organic framework (COF). These nanospheres show increased peroxidase (POD) and oxidase (OXD) activities in the tumor microenvironment, generating reactive oxygen species (ROS) that help eliminate tumor cells. Under normal conditions, they display catalase (CAT) and superoxide dismutase (SOD) activities, promoting antioxidative protection. Their porous structure and π–π/hydrophobic interactions allow for the loading of the chemotherapeutic agent doxorubicin (DOX). The nanospheres are then enveloped by tumor cell membranes, stabilizing the drug load and enabling targeted drug delivery with pH‐sensitive release. This targeted system induces ferroptosis in tumor cells and activates a strong anti‐tumor immune response, leading to enhanced immunotherapy for breast cancer and reduced tumor metastasis to the lungs. Importantly, the varied enzymatic activities of the nanomedicine system help mitigate the cardiotoxicity of DOX chemotherapy, improving cancer treatment while minimizing side effects. This approach introduces a nano‐enzyme drug system with distinctive activities and innovative preparation, setting a new standard for efficient, low‐toxicity cancer therapy.