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

Abstract

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 via a hydrothermal method, utilizing Artemisia argyi 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 A. muciniphila 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.