Phellinus igniarius-derived carbon dots suppress liver cancer through the ROS/MAPK signaling axis

Liver cancer is one of the most common and highly lethal malignancies worldwide, and current therapeutic strategies remain limited, posing significant clinical challenges. Thermal processing of natural products is not only used for the extraction of active constituents, but may also induce structural reconstruction and bioactivity transformation of endogenous components. Recent studies have demonstrated that certain natural products can generate carbon dots (CDs) with specific biological activities under high-temperature conditions, suggesting that these nanoparticles may serve as novel active components formed during thermal processing. Phellinus igniarius, a traditional medicinal fungus, possesses anti-inflammatory and immunomodulatory activities. However, the formation of carbon dots during its thermal processing and their biological functions have not been systematically investigated. In this study, Phellinus igniarius-derived carbon dots (PI-CDs) were synthesized using a hydrothermal method, and their antitumor activities and underlying mechanisms were systematically evaluated both in vitro and in vivo. The results showed that PI-CDs exhibited uniform nanoscale morphology with good dispersibility. In vitro experiments demonstrated that PI-CDs significantly inhibited the viability, migration, and invasion of liver cancer cells in a concentration-dependent manner. Transcriptomic analysis revealed significant enrichment of MAPK signaling and apoptosis-related pathways, which was further supported by increased phosphorylation of p38 and JNK. Mechanistically, PI-CDs induced intracellular reactive oxygen species (ROS) accumulation, promoted mitochondrial membrane depolarization, and triggered apoptotic cell death. Furthermore, PI-CDs effectively suppressed tumor growth in vivo xenograft model without obvious systemic toxicity. Collectively, these findings suggest that PI-CDs exert antitumor effects through oxidative stress-associated MAPK signaling and mitochondria-dependent apoptosis. This study demonstrates that carbon dots generated from the medicinal fungus Phellinus igniarius possess significant anti-liver cancer activity and reveals a ROS/MAPK-associated mechanism underlying their biological effects. More importantly, our findings highlight thermal processing as a promising strategy for transforming traditional medicinal resources into functional nanomaterials with intrinsic therapeutic potential, thereby providing a new perspective for the development of natural product-derived nanomedicines for cancer treatment.