Abstract
Gastric cancer (GC) remains a major global health problem and demands more effective therapeutic approaches. In this study, we developed a novel biomimetic nanovesicle system-cancer cell membrane-coated liposomal nanocarriers loaded with silibinin (CLip@Sil)-designed for targeted therapy against GC. By integrating network pharmacology with transcriptomic profiling, we identified 13 key target genes, significantly enriched in the PI3K/AKT and IL-17 signaling pathways, with HSP90AA1 emerging as a central regulatory node. Further mechanistic investigation revealed that silibinin exerts its anticancer effect by modulating the SNHG1/miR-383-5p/HSP90AA1 competing endogenous RNA (ceRNA) axis, thereby suppressing the PI3K/AKT pathway. The engineered CLip@Sil system demonstrated enhanced tumor-targeting capacity via its biomimetic cancer-membrane coating, enabling selective drug delivery and accumulation in tumor tissues. In vitro studies confirmed that CLip@Sil inhibited GC cell proliferation, migration, and invasion, while promoting apoptosis. In vivo, CLip@Sil significantly suppressed primary tumor growth and lung metastasis, extended overall survival, and exhibited minimal systemic toxicity. These findings highlight the value of combining competing endogenous RNA regulatory networks with nanomaterial based targeted delivery systems for GC therapy. The CLip@Sil platform offers a promising direction for the future development of precise and biomimetic nanotherapeutics in oncology.