Advances of Chinese herbal medicine-derived polysaccharides as carrier-free and carrier agents in anti-melanoma therapy

Melanoma, a highly aggressive malignancy with increasing global incidence, faces significant therapeutic challenges due to drug resistance, systemic toxicity, and immunosuppressive tumor microenvironment. Despite advances in targeted therapies and immunotherapies, the need for safer and more effective treatment options remains urgent. Chinese herbal medicine-derived polysaccharides (CHMPs), characterized by their natural origin, biocompatibility, and multifaceted bioactivities, have garnered increasing attention as promising candidates for melanoma therapy due to their low toxicity and multi-targeting capabilities. In this review, the dual roles of CHMPs with varied origins in anti-melanoma treatment will be systematically elucidated. As carrier-free anti-tumor agents, CHMPs exert anti-melanoma effects through multiple mechanisms, including immune modulation, apoptosis induction, cell cycle arrest, inhibiting tumor angiogenesis, and regulating signaling pathways. Moreover, as intelligent carriers, CHMPs can be chemically modified or physically assembled into targeted delivery systems, enhancing drug stability and bioavailability while minimizing off-target toxicity. Finally, current challenges for CHMPs in anti-melanoma treatments, such as structural heterogeneity, unclear structure-activity relationships, and limited clinical translation, will be outlined, and future efforts are also discussed. By bridging traditional herbal medicine and modern biomaterials science, we expect this review not only to provide a roadmap for developing CHMP-based multifunctional biomaterials platforms but also to inspire novel strategies to overcome current therapeutic bottlenecks in melanoma management, paving the way for safer and more effective treatments.