Antiangiogenic <i>Antheraea pernyi</i> Silk Fibroin Nanocarrier As an Advanced Dual-Gene Delivery Platform for Lung Tumor Suppression

The cationic <i>Antheraea pernyi</i> silk fibroin (CASF)-bridged endostatin peptide 2 (ES2) electrostatically coated the inhibitor of growth 4 (ING4)/interleukin-24 (IL-24) dual-gene coexpression plasmid DNA (pDNA) to construct a CASF-ES2/pDNA nanocarrier, which significantly enhanced gene expression and induced apoptosis by strengthening cell adhesion and endocytosis. The continuously released ES2 contributed to its specific action on HUVECs, including inducing apoptosis and hindering migration, invasion, and tube formation, as well as inhibiting angiogenesis in the chorioallantoic membrane. In the treatment of mice with A549 xenograft tumors, CASF-ES2/pDNA arrested the growth cycle of tumor cells and activated the Bcl-2/Bax/C Caspase-3 apoptotic pathway, promoting cell apoptosis and tissue collapse. Additionally, the released ES2 prevented the formation of tumor neovasculature, cut off the nutrient channels for tumor growth, and synergistically inhibited the development and metastasis of xenograft tumors. This safe and antiangiogenic gene vector shows great promise for application in long-term antitumor and antimetastatic therapy.