TLyp-1-modified exosome–mediated delivery of circRAPGEF5 ASO inhibits lung adenocarcinoma metastasis via regulating the miR-570-3p/SPP1 axis

Exosome circRAPGEF5 promotes lung adenocarcinoma (LUAD) metastasis and may serve as an intervention target, but its mechanism of action is unclear. Consequently, using engineered exosomal preparations of circular RNAs for delivery into tumor cells represents a safe and effective strategy for cancer treatment. The results confirmed the successful construction of tLyp-1-exosome (EXO)-circRAPGEF5 antisense oligonucleotides (ASO). tLyp-1 modified exosomes efficiently targeted LUAD tumors <i>in vivo</i> and <i>in vitro</i>. The tLyp-1-EXO-circRAPGEF5 ASO significantly reduced the proliferation, invasion, migration, and levels of N-cadherin and vimentin in A549 and HCC827 cells. circRAPGEF5 acted as an miR-570-3p sponge, facilitating LUAD progression, and miR-570-3p directly regulated secreted phosphoprotein 1(SPP1) expression. The knockdown of circRAPGEF5 inhibited LUAD progression via the miR-570-3p/SPP1 axis. The tLyp-1-EXO-circRAPGEF5 ASO did not damage BEAS-2B (Human Normal Lung Epithelial) cells. Nude mouse model experiments using hematoxylin and eosin staining and biochemical indexes demonstrated that tLyp-1-EXO-circRAPGEF5 ASO significantly inhibited LUAD metastasis and did not cause biological damage to vital organs. This study clarified the mechanism of tLyp-1-EXO-circRAPGEF5 ASO in inhibiting LUAD metastasis, indicating that circRAPGEF5 may serve as a new intervention target for LUAD metastasis.