Investigation of the Anti-Lung Cancer Activity and Mechanism of Umbilical Cord Blood Stem Cell-Derived NK Cell Exosomes

Objective In order to determine the therapeutic efficacy and mechanism of action of natural killer cell-based exosomes from umbilical cord blood stem cells (UCB-NK-EXO) in a lung cancer model.Methods Umbilical cord blood stem cells isolated from umbilical cord blood were expanded into NK cells using NK serum-free medium containing IL-21. The cell supernatant was collected to extract and identify exosomes. The effect of exosomes on the proliferation of A549 cells was detected by CCK8 assay; the effect of exosomes on the apoptosis of A549 cells was detected by flow cytometry; the uptake of exosomes by cells was observed using confocal microscopy. The enrichment of UCB-NK-EXO in tumor sites of tumor-bearing mice was evaluated by in vivo small animal imaging, and tumor growth was observed while serum liver and kidney function indicators were detected; the expression levels of apoptosis-related signaling molecules in mouse tumor tissues were detected by Western blot.Results There were no significant differences in particle size and zeta potential between UCB-NK-EXO and NK92-EXO. However, after UCB-NK-EXO treatment, the viability of A549 cells was significantly lower than that of the NK92-EXO treatment group (P < 0.001). UCB-NK-EXO accumulated at the tumor site, induced tumor cell apoptosis, and significantly inhibited tumor growth (P < 0.001) while prolonging survival, with effects superior to those of Doxorubicin (DOX). Additionally, UCB-NK-EXO did not cause significant body weight loss or liver and kidney damage. Western blot results showed that UCB-NK-EXO contained cytotoxic proteins such as Granzyme B and Perforin, and significantly upregulated the expression of apoptosis-related proteins, including Caspases, in mouse tumor tissues.Conclusion UCB-NK-EXO effectively inhibited the growth of A549 lung cancer both in vitro and in vivo, and accumulated at the tumor site in mice. The mechanism involves the delivery of cytotoxic proteins to tumor cells, activation of the Caspase-dependent apoptosis pathway, and subsequent induction of tumor cell apoptosis. UCB-NK-EXO demonstrates superior antitumor efficacy and a more favorable safety profile compared to the conventional chemotherapeutic agent doxorubicin.