Copper-Doped Luteolin Carbon Dots with Antitumor Properties Based on the Induction of Immunogenic Cell Death

Carbon dots as drug carriers have received increasing attention in nanotherapy. However, the use of chemical small molecules or polymers as precursors to carbon dots often leads to toxicity, thus limiting their practical application. In contrast, herbs are biocompatible plants with complex active ingredients, making them attractive candidates for carbon dot precursors. In this paper, we prepared antitumor carbon dots (LuCDs) using a hydrothermal method and luteolin extract as a precursor. Furthermore, by modifying copper ions on the surface of LuCDs, we obtained Cu-LuCDs. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) analysis results showed that both LuCDs and Cu-LuCDs effectively inhibited the proliferation of CT26 colon cancer cells. Additionally, these modified carbon dots exhibited photothermal conversion properties not present in the precursor alone. Under 808 nm optical excitation, they achieved photothermal conversion powers of 55 and 56%, respectively. The Cu-LuCDs effectively decompose hydrogen peroxide, generating cytotoxic •OH and oxygen through Fenton-like reactions, thereby alleviating tumor hypoxia and inhibiting the expression of hypoxia-inducing factor HIF-1α. Immunofluorescence analysis confirmed that both LuCDs and Cu-LuCDs induced immune cell death and activated systemic immune activity. When combined with the immune adjuvant αPD-L1, Cu-LuCDs successfully ablated primary tumors and significantly inhibited the growth of metastatic tumors (distal tumors). The design and analysis of the antitumor activity of Cu-LuCDs provide important inspiration for the application of herbal carbon dots.