title: Alkane-modified low-molecular-weight polyethylenimine with enhanced gene silencing for siRNA delivery.
abstract: Small interfering RNA (siRNA) has tremendous potential as a therapeutic agent for diverse diseases; however, due to its susceptibility to degradation and poor cellular uptake, the low efficiency of administration has been the most important limiting factor for clinical applications of siRNA. Herein, we synthesized alkyl chain modified low-molecular-weight polyethylenimines (LMW PEIs) and found that hydrophobically modified PEIs displayed enhanced efficiency in siRNA-mediated knockdown of target genes. To elucidate the mechanism for increased delivery, we characterized the polymers' physicochemical properties and bioactivity via nuclear magnetic resonance (NMR), gel retardation assay, dynamic laser scattering (DLS) analysis, confocal laser scanning microscopy and flow cytometry. The hydrophobic modification reduced siRNA binding affinity but facilitated the formation of nanoparticles in contrast to the original PEI. The PEIs with eight and thirteen alkyl tails were able to self-assemble into nanoparticles and yielded higher cellular uptake, which leaded to even similar efficiencies of 80-90% knockdown as Lipofectamine™ 2000 control. These results suggested that the status of polymers in aqueous solution, which depended on the degree of hydrophobic modification, played an important role in the uptake of siRNA. Therefore, we provided new information on the role of hydrophobic content in the enhanced gene silencing activity.
authors.affiliation: Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou 510530, China.
authors.forename: Gaoyang
authors.initials: G
authors.lastname: Guo
authors.forename: Li
authors.initials: L
authors.lastname: Zhou
authors.forename: Zhifei
authors.initials: Z
authors.lastname: Chen
authors.forename: Weilin
authors.initials: W
authors.lastname: Chi
authors.forename: Xiuqun
authors.initials: X
authors.lastname: Yang
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.forename: Biliang
authors.initials: B
authors.lastname: Zhang
mesh_terms: D000178:Acrylamides / Q000737:chemistry*; D045744:Cell Line, Tumor; D002463:Cell Membrane Permeability; D020868:Gene Silencing; D006461:Hemolysis; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D008970:Molecular Weight; D011094:Polyethyleneimine / Q000737:chemistry*; D034741:RNA, Small Interfering / Q000008:administration & dosage / Q000737:chemistry*; D014162:Transfection
chemical_list: D000178:Acrylamides; D034741:RNA, Small Interfering; D011094:Polyethyleneimine