Perylene Tetracarboxylic Dianhydride Carbon Dots Deplete Glutathione to Induce Immunogenic Cell Death in Tumor Cells.

High glutathione levels in the tumor microenvironment drive tumor resistance and proliferation, making glutathione depletion a key cancer therapeutic strategy. Existing inhibitors face issues such as poor specificity and biocompatibility, creating a need for new formulations with high targeting, low toxicity, and efficient depletion. This study synthesized carbon dots (PCDs) via the hydrothermal method using 3,4,9,10-perylenetetracarboxylic dianhydride as a precursor. PCDs oxidize glutathione for depletion via intrinsic redox properties and act as efficient glutathione probes with fluorescence and colorimetric detection limits of 0.527 and 13.11 μM, respectively, showing excellent stability in complex biological environments. Under an 808 nm near-infrared laser, PCDs exhibit 41.88% photothermal conversion efficiency. PCDs induce tumor cell apoptosis by depleting glutathione with enhanced antitumor effects under photothermal therapy synergy. They disrupt tumor redox homeostasis to trigger immunogenic cell death, promote dendritic cell maturation, polarize M2 macrophages to M1, and activate T cell-mediated immunity. In vivo dual-tumor models confirmed that PCDs combined with αPD-L1 efficiently ablate primary tumors, inhibit distal growth, and exert systemic antitumor immune effects. This simple-synthesized, biocompatible PCDs integrate detection and antitumor functions, offering new ideas for next-generation nanodiagnostic/therapeutic materials and combination therapy.