title: Poly(ester amine) synthesized from trimethylolpropane triacrylate and spermine as an efficient siRNA carrier.
abstract: Small interfering RNA (siRNA) is a promising candidate for gene therapy due to the strong and specific gene silencing effects. However, to effectively silence any protein, lack of an efficient delivery system is major obstacle for siRNA therapeutics. In the present study, we report on the development of a novel poly(ester amine) (PEA) as an efficient siRNA carrier. The PEA was prepared by a Michael addition reaction between trimethylolpropane triacrylate (TT) and spermine (SPE). The composition of the PEA was characterized by 1H nuclear magnetic resonance (1H NMR) and the molecular weight was measured using gel permeability chromatography (GPC). This TT-SPE effectively condensed siRNA into a compact nanoscale structure (size: 76 nm) with homogenous size distribution and provided superior protection of siRNA from RNase A enzyme. Furthermore, TT-SPE/ siRNA complexes showed good intracellular uptake and had efficacious gene silencing effect with low toxicity compared to PEI 25K. These findings demonstrated that TT-SPE has potential as an alternative to PEI 25K for siRNA-based gene therapy.
authors.affiliation: State Key Laboratory of Natural Medicines, Department of Pharmaceutics, China Pharmaceutical University, Nanjing 210009, PR China.
authors.forename: You-Kyoung
authors.initials: YK
authors.lastname: Kim
authors.forename: Chong-Su
authors.initials: CS
authors.lastname: Cho
authors.forename: Myung-Haing
authors.initials: MH
authors.lastname: Cho
authors.forename: Hu-Lin
authors.initials: HL
authors.lastname: Jiang
mesh_terms: D000179:Acrylates / Q000737:chemistry*; D000588:Amines / Q000737:chemistry*; D001672:Biocompatible Materials; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000378:metabolism; D002470:Cell Survival; D002845:Chromatography; D005782:Gels; D020868:Gene Silencing; D015316:Genetic Therapy / Q000379:methods; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D049329:Nanostructures / Q000737:chemistry; D010539:Permeability; D011091:Polyesters / Q000737:chemistry*; D034741:RNA, Small Interfering / Q000737:chemistry*; D012259:Ribonuclease, Pancreatic / Q000737:chemistry; D013096:Spermine / Q000737:chemistry*
chemical_list: D000179:Acrylates; D000588:Amines; D001672:Biocompatible Materials; D005782:Gels; D011091:Polyesters; D034741:RNA, Small Interfering; D013096:Spermine; C027993:trimethylolpropane triacrylate; D012259:Ribonuclease, Pancreatic