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 H2O2, nanozyme with peroxidase (POD)-like activity for decomposing H2O2 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 H2O2 (∼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 (Km = 0.58 mM) under weak acidic TME, therefore to efficiently convert the trace amounts of endogenous H2O2 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.