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

Abstract

BackgroundGastric 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.MethodsDue 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.ResultsOur 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.ConclusionThis collagen-based delivery system may facilitate the pathogenesis elucidation and design of effective therapies against gastric cancer.

New Developments in Medical Applications of Hybrid Hydrogels Containing Natural Polymers

“…Krebs et al [399] showed the collagen chains ability to locally load siRNA (small interfering RNA) and then release it in a controlled manner in order to extend the effect directly at the specific target. Peng et al [400] tested collagen based hybrid hydrogels for the Id1-siRNA targeting and its delivery and sustained release for the treatment of gastric cancer. To improve the siRNA delivery by stimulating the target of Id1-siRNA into the defect cells and prolonging the silencing effect, cationic PEI was further engaged for scaffold modification.…”

Applications of Lipidic and Polymeric Nanoparticles for siRNA Delivery

“…Collagen is another biologically compatible and safe natural polymer and is a suitable carrier for drug delivery. In a study performed by Peng et al, localized and sustained release of siRNA-loaded collagen formulations were prepared for use in vivo gastric cancer, and positive results were obtained [57].…”

Gene Silencing via PDA/ERK2‐siRNA‐Mediated Electrospun Fibers for Peritendinous Antiadhesion

“…[8,29] Scaffold-mediated RNA interference has been carried out through the surface immobilization or direct bulk encapsulation of siRNA in hydrogels, [30] nanofibers, [11] and sponge-based constructs. [8,29] Scaffold-mediated RNA interference has been carried out through the surface immobilization or direct bulk encapsulation of siRNA in hydrogels, [30] nanofibers, [11] and sponge-based constructs.…”