Mercaptosuccinic Acid-Based Carbon Quantum Dots as Peroxidase-like Nanozymes Inducing Cell Pyroptosis for Tumor-Specific Therapy

Nonspecific targeting and low efficiency are challenges to face in tumor treatment. By utilizing the unique tumor microenvironment (TME) of acidic condition and overexpressed H 2 O 2, nanozyme with peroxidase (POD)-like activity for decomposing H 2 O 2 into extremely toxic hydroxyl radicals ( • OH) to destroy cancer cells in situ is promisingly addressed for tumor-specific treatment. However, the catalytic therapeutic efficiency of most current POD-like nanozymes are usually counteracted by the weak acidity (pH 6.0–6.7) and insufficient H 2 O 2 (∼50–100 μM) in TME. Herein, we report a mercaptosuccinic acid-derived carbon quantum dot (MA-CQD) nanozyme, which is highly biocompatible and possesses superior POD-like activity ( K m = 0.58 mM) under weak acidic TME, therefore to efficiently convert the trace amounts of endogenous H 2 O 2 for tumor treatment, while posing minimal nonspecific damage to normal tissues with neutral condition (pH 7.4). MA-CQDs are confirmed to cause an intensive caspase-1/gasdermin D-mediated cell pyroptosis through produced reactive oxygen species, providing an effective way for tumor therapy. Our MA-CQDs nanocatalyst demonstrates a desirable tumor suppression rate. This work offers a prospective mode for the tumor-specific therapy and inspires the development of cancer-specific pyroptotic nanomedicine.