pH-responsive doxorubicin-loaded <i>Artemisia argyi</i> carbon dots: enhanced targeted therapy for hepatocellular carcinoma

Hepatocellular carcinoma (HCC), a lethal form of liver cancer within the gastrointestinal tract, demonstrates dismal survival rates and challenging treatment prospects. Doxorubicin (DOX) continues to be extensively employed as a chemotherapeutic drug for hepatocellular carcinoma in clinical practice. Nevertheless, its lack of selective targeting leads to non-specific killing of normal healthy cells, thereby inducing severe adverse reactions. Carbon dots (CDs) with biocompatibility and low toxicity have attracted much attention in cancer treatment. We demonstrate an eco-friendly and straightforward synthesis of CDs with superior biocompatibility <i>via</i> a hydrothermal method, utilizing <i>Artemisia argyi</i> as the carbon precursor, and doxorubicin-loaded carbon dots (CDs-DOX) provide a novel strategy for liver cancer treatment. Compared with DOX, CDs-DOX showed more significant anti-tumor advantages. CDs-DOX enhanced the relative abundance of <i>A. muciniphila</i> in the intestinal microbiota, reshape the homeostasis of intestinal flora in mice, and significantly enhance the intestinal barrier function. The antitumor effects of CDs-DOX against HCC involve regulation of pivotal genes and alteration of the tumor microenvironment. In addition, CDs-DOX significantly reduce DOX heart and liver toxicity, reduce treatment-related adverse reactions, and provide a safer and more efficient new strategy for combined treatment of tumors.