Engineered Plant-Derived Extracellular Vesicles: A Novel Strategy for Tumor-Targeted Therapy.

Cancer remains a leading cause of premature death worldwide, posing a significant burden due to its high incidence and mortality. Radiotherapy and chemotherapy remain the most well-established and effective modalities in the current oncological therapeutic arsenal. However, their efficacy is often limited by toxicities owing to their non-selective targeting of rapidly dividing cells and consequent damage to healthy tissues. In recent years, advances in nanomedicine and biotechnology have drawn increasing attention to plant-derived extracellular vesicles (PDEVs) as an emerging, promising strategy for cancer therapy. As novel therapeutic vehicles, PDEVs offer key advantages, including high biocompatibility and low immunogenicity. However, their clinical translation has been significantly hampered by inherent limitations, including insufficient targeting specificity, low and uncontrollable drug-loading efficiency, and challenges in large-scale production and standardization. Current research is actively focused on overcoming these drawbacks through engineering strategies, for instance, surface modification with targeting peptides or antibodies to enhance targeting, alongside optimization of production and drug-loading processes. These developments underscore the potential of PDEVs as a promising platform for next-generation targeted cancer therapeutics. This review provides a comprehensive overview of PDEVs, covering their isolation, biogenesis, physicochemical properties, and anticancer applications. While summarizing these fundamental aspects, this review focuses on engineering strategies to enhance their active targeting capacity, offering theoretical insights to support their future role in cancer treatment.