Alkylimidazolium End-Modified Poly(ethylene glycol) To Form the Mono-ion Complex with Plasmid DNA for in Vivo Gene Delivery

Abstract

In this study, we consider that the decrease in the transfection activity of polycations in vivo, compared with that in vitro, results from their polyion complex formation. Namely, owing to cross-linking between polycations and plasmid DNAs (pDNAs), the disadvantage of in vivo gene delivery mainly stems from the difficulty in controlling the properties of the resulting polyion complex at the nanoscale size. To avoid the cross-linking by polycations, we have establish the concept of "mono-ion complex" formation between pDNA and a monocationic biocompatible polymer. Here we have synthesized alkylimidazolium end-modified poly(ethylene glycol), that is, R-Im-PEG, and have tuned the electrostatic interaction between the resulting alkylimidazolium group and the phosphate group of pDNA by the length of the alkyl chain to achieve "mono-ion complex" formation with pDNA for in vivo gene delivery. Instead of a polyion complex, our original concept of the "mono-ion complex" consisting of the Bu-Im-PEG and pDNA is expected to offer unique tools to break through the barriers of in vivo gene delivery. As well as the field of gene delivery, this study is considered to have exploded the common sense that it is impossible to form not a polyion complex but a "mono-ion complex" under aqueous conditions for all fields of the modification of biomacromolecules.

Structure-property relationship for in vitro siRNA delivery performance of cationic 2-hydroxypropyl-β-cyclodextrin: PEG-PPG-PEG polyrotaxane vectors

“…We conclude the silencing efficiency of PR + :siRNA complexes is most highly dependent on strong electrostatic interaction between the PR + condensing agent and siRNA, with the formation of a highly ordered lamellar architecture of the complex as a factor of secondary importance. The electrostatic interaction dependence of these two key parameters, i.e., threading efficiency and the length of the EO block, to produce a lamellar architecture is a direct result of the increased rigidity of the threaded PR + [54–56]. …”

Plasmid DNA Mono-Ion Complex for in Vivo Sustainable Gene Expression

“…Recently, to overcome the structural properties of PICs, such as a tendency for large particle size by cross-linking between polycations and pDNAs, we have reported the concept of mono-ion complex (MIC) between our original monocationic PEG and pDNA. 20 As a stabilized MIC by hydrogen bond with an adenine base in adenine–thymine base pair of pDNA, we have already designed ω-amide-pentylimidazolium end-modified PEG, i.e., APe-Im-PEG. 21…”

Cationic gemini lipids containing polyoxyethylene spacers as improved transfecting agents of plasmid DNA in cancer cells

“…The higher charge density and lower hydrophobicity of the head groups might have also played a role. 31 In addition, lipoplexes formed from GCLs with two imidazolium cationic head groups rearrange in cluster-type lamellar structures, their TE being controlled by the spacer length between the imidazolium head groups. 18 In the present study, we use the lipoplex formed by pEGFP-C3 plasmid DNA (pDNA) and mixed liposomes, containing a GCL of the bis(hexadecyl dimethyl ammonium) oxyethylene series, referred to as (C 16 Am) 2 (C 2 O) n , (where n is the oxyethylene spacer length, n ¼ 1, 2 or 3, between the ammonium heads) and DOPE as the helper zwitterionic lipid.…”