Enhanced tumor self-targeting of lemon-derived extracellular vesicles by embedding homotypic cancer cell membranes for efficient drug delivery

Plant-derived nanovesicles (PDVs) as nanodrug delivery carriers have gained recognition due to their satisfactory biosafety. However, there remains a challenge to target tumor sites accurately due to the uncertain membrane protein components on the surface of vesicles. Herein, a composite nanodrug delivery system by encapsulating the chemotherapy drug DOX is establish to efficiently target breast cancer. The novel nanoplatform (LEVBD) is formed by embedding the membrane fragments from breast cancer cell with the lemon-derived nanovesicles (LEVs) as the foundational skeleton. LEVBD reveal wonderful homologous tumor targeting due to fusion of cancer cell membrane components with LEVs, and the encapsulation of hybrid vesicles facilitates the transcellular transport of drugs. After intravenous injection, LEVBD could efficiently and selectively home to homologous tumor sites even under competition from heterologous tumors and significantly inhibit tumor growth without any observable toxic side effects. The doping of homologous cancer cell membranes provides a paradigm for the precise delivery of drug delivery vehicles using plant-derived vesicles as the backbone.