Engineering exosome-based delivery of IL-37 to enhance cytokine stability and antitumor activity in vitro and in vivo.

Interleukin-37 (IL-37) is an anti-inflammatory cytokine with antitumor activity, yet its clinical utility is constrained by poor bioavailability and rapid degradation. This study engineered NCI-H226-derived exosomes as IL-37 nanocarriers and evaluated their anticancer efficacy in cellular and hepatic carcinoma models. Exosomes were isolated using Total Exosome Isolation (TEI) reagent and qEV10 size-exclusion chromatography. IL-37 loading by sonication achieved >80% encapsulation efficiency and sustained release, with cumulative release of 65.11 ± 0.25% and 59.95 ± 0.43% for qEV10- and TEI-isolated exosomes, respectively. IL-37-loaded exosomes exhibited greater cytotoxicity than free IL-37 across tested cancer cells. In the DEN-1 rat model, IL-37-loaded exosomes significantly reduced tumor burden, liver fibrosis, and serum ALT, AST, ALP level. Gene expression analysis showed normalization of inflammatory (IL-6, IL-1β) and fibrotic (α-Sma, Col1α1) markers. These findings support further investigation of exosome-based IL-37 delivery as a better immunotherapy platform.