Selenomethionine-Conjugated Extracellular Vesicles for ROS-Mediated Cell Apoptosis

Selenomethionine (SeM) holds great potential applications in tumor therapy. However, the tumor-targeting ability of SeM in vivo remains challenging. Herein, we utilize extracellular vesicles (EV) as tumor-targeted drug delivery systems to achieve enhanced specific targeting and antitumor efficacy. The carboxyl groups of SeM are conjugated with the amino groups of EV derived from low-pH culture medium reprogrammed CT26 cells (LEV) to obtain the SeM-based formulations (SMLEV), which can actively target tumor cells and enhance uptake efficacy through specific behaviors of LEV to their parent cells. Mechanistic studies indicate that SMLEV can induce reactive oxygen species (ROS) overproduction, mitochondrial dysfunction, as well as Caspase-9 and Caspase-3 activation. Here, SMLEV exhibit enhanced cytotoxic potential toward colon tumor (CT26) cells. After systemic administration, the growth of tumors is inhibited in vivo using CT26 tumor-bearing mice. Our findings can provide insights and a strategy in developing SeM delivery for tumor treatment.