Engineered Plant-Derived Extracellular Vesicles as Targeted Drug Carriers in Cancer Therapy

Breast cancer remains one of the most prevalent and deadly cancers worldwide, with many patients experiencing limited treatment efficacy and adverse side effects from conventional chemotherapy. These limitations are primarily due to poor drug targeting, low bioavailability, and systemic toxicity. To address these challenges, extracellular vesicles (EVs) have emerged as promising drug delivery systems owing to their innate biocompatibility, cellular delivery capabilities, and ability to carry diverse bioactive molecules. Among various EV sources, plant-derived EVs offer unique advantages, including low immunogenicity, cost-effective scalability, and absence of animal-derived components, making them highly suitable for clinical applications. In this study, we developed a plant-derived EV-based drug delivery platform using black soybean-derived extracellular vesicles (Blex). A high yield of Blex was successfully purified from black soybean and subsequently loaded with a substantial amount of chemotherapeutic agent doxorubicin (Dox) through passive diffusion. To achieve tumor-targeting specificity, Blex were chemically engineered by covalently conjugating the cyclic RGD (cRGD) peptide, which binds to integrin receptors overexpressed in many cancer types, including breast cancer. The resulting Dox-loaded Blex engineered with cancer cell-targeting cRGD (Blex(Dox)_cRGD) demonstrated enhanced cellular uptake, improved cytotoxicity against breast cancer cells, and greater tumor reduction in vivo. This work highlights the potential of combining drug loading with surface engineering to improve therapeutic outcomes while minimizing systemic toxicity. Overall, our findings underscore the utility of plant-derived EVs as a scalable, biocompatible platform for targeted chemotherapy. This strategy provides a foundation for next-generation nanomedicine development, offering a therapeutic approach for breast cancer and other solid tumors.