Sustained delivery of siRNA/PEI complex from in situ forming hydrogels potently inhibits the proliferation of gastric cancer

Abstract

Background: Gastric cancer remains a major cause of mortality and morbidity worldwide. In recent years, gene-based therapeutic strategies were confirmed promising in cancer inhibition and attracted great attention. RNA interference (RNAi) is a powerful tool for gene therapy and has been widely employed to aid in treatment for various diseases, especially cancers. However, effective delivery of small interfering RNA (siRNA) to target cells in vivo remains a challenge for that it is prone to degradation and only lasts a few days in rapidly dividing cells. Methods: Due to its biocompatibility and well-established safety profile, collagen represents a favourable matrix for in-site drug delivery. In the study, collagen hydrogel was used as carriers to test the feasibility of localized and sustained delivery of Id1-targeted siRNA for in vivo gastric cancer inhibition. To enhance the siRNA delivery, cationic polyethylenimine (PEI) was further emplored for scallold modification. The efficacy of siRNA delivery and cancer inhibition were evaluated with multimodality of mehods in vitro and in vivo. Results: Our results showed that addition of polyethylenimine (PEI) to collagen can facilitate entry of Id1-siRNA into target cells, prolong the silencing effect, and further inhibit tumor growth both in vitro and in vivo. Conclusion: This collagen-based delivery system may facilitate the pathogenesis elucidation and design of effective therapies against gastric cancer.