Application of natural products combined with plant-derived extracellular vesicles in cancer therapy

Cancer remains a leading cause of mortality worldwide. The success of plant-derived chemotherapeutic agents, such as paclitaxel and vinblastine, underscores the significant potential of plant-derived natural products (PDNPs) in oncology. Despite this success, the poor solubility, metabolic instability, and nonspecific distribution of many PDNPs pose a fundamental barrier to their full clinical potential. Plant-derived extracellular vesicles (PDEVs) have garnered considerable attention as biocompatible nanocarriers, and numerous reviews have examined their biological activities and delivery applications. However, few have systematically addressed their synergistic combination with PDNPs in cancer therapy. This review distinguishes itself by centering on the synergistic interplay between PDNPs and PDEVs as an integrated therapeutic strategy. Specifically, we examine: (1) how PDEVs enhance the bioavailability and anticancer efficacy of PDNPs by improving their solubility, stability, and targeted delivery, and (2) how the intrinsic antitumor activity of PDEVs complements that of PDNPs to achieve enhanced therapeutic efficacy and reduced systemic toxicity compared with either agent alone. By integrating current evidence on the combined use of PDNPs and PDEVs, this review aims to enhance the field's understanding of the progress made by PDNPs and PDEVs in cancer therapy, clarify their mechanisms of action, and identify the critical challenges facing the current research stage.