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.
Highlights
Gastric cancer remains a major cause of mortality and morbidity worldwide
Effective delivery of small interfering RNA to target cells in vivo is far from realizing its full therapeutic potential because it is prone to degradation by RNases [5], the silencing effect only lasts a few days in rapidly dividing cells [6], and retention of the siRNA at a specific location is difficult [7]
We mainly investigated the feasibility of localized and sustained delivery of Inhibitor of DNA binding 1 (Id1)-targeted siRNA incorporated within collagen, the characteristic of siRNA release profile, and its effect on growth and migration ability of gastric cancer cells both in vitro and in vivo
Summary
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. Effective delivery of small interfering RNA (siRNA) to target cells in vivo is far from realizing its full therapeutic potential because it is prone to degradation by RNases [5], the silencing effect only lasts a few days in rapidly dividing cells [6], and retention of the siRNA at a specific location is difficult [7]. Collagen has been shown to retain siRNA locally and release it in a sustained manner to prolong the effect directly at the specific site by Krebs and his colleagues [11] Through this delivery system, novel candidates can be tested for effective therapies against gastric cancer before further clinical application. Characteristics of this strategy for interference and therapeutics on gastric cancer, both in vitro and in vivo, needs to be demonstrated
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