Huifang Yang, Yiran Wang, Yilin Wang, Kexin Tang, Jing Guo, Tong Li
Resveratrol (3,5,4'-trihydroxy-trans-stilbene), a natural polyphenol, has garnered significant attention in oncology for its multifaceted antitumor mechanisms, including apoptosis induction, angiogenesis suppression, and immunomodulation. Despite its therapeutic potential, clinical translation remains constrained by pharmacokinetic limitations such as rapid metabolism, poor aqueous solubility, and low bioavailability. Recent advancements in biomaterial-based co-delivery systems have emerged as a transformative strategy to circumvent these challenges while amplifying tumor-specific cytotoxicity. By integrating resveratrol with chemotherapeutics, photothermal agents, metal complexes, or covalent organic frameworks (COFs), these systems synergistically enhance therapeutic efficacy through improved drug stability, targeted delivery, and stimuli-responsive release. Furthermore, multifunctional platforms combining photothermal ablation, ROS modulation, and immunotherapy exhibit promise in overcoming multidrug resistance and reprogramming immunosuppressive microenvironments. However, critical gaps persist in understanding structure-activity relationships, long-term biosafety profiles, and clinical scalability. This review comprehensively summarizes the current progress in resveratrol co-delivery systems, emphasizing their mechanisms, preclinical outcomes, and technological innovations. Future directions should prioritize interdisciplinary approaches, including AI-driven nanomaterial design, pharmacogenomic stratification, and biomarker-driven clinical trials, to bridge the gap between preclinical promise and therapeutic reality. By harmonizing resveratrol's phytochemical efficacy with advanced biomaterial engineering, these co-delivery systems hold transformative potential for precision oncology.