title: The role of PEG architecture and molecular weight in the gene transfection performance of PEGylated poly(dimethylaminoethyl methacrylate) based cationic polymers.
abstract: In this study, we report the synthesis of well-defined model PEGylated poly(dimethylaminoethyl methacrylate) based cationic polymers composed of different PEG architecture with controlled PEG and nitrogen content via reversible addition-fragmentation chain transfer (RAFT) polymerization, and study the effects of PEG architecture and polymer molecular weight on gene delivery and cytotoxicity. Investigation of the physico-chemical interactions of these model cationic polymers with DNA demonstrated that all these polymers effectively complexed with DNA, and PEG topology did not significantly affect the abilities of the polymers to complex and release DNA. However the size and zeta potential of the complexes were found to be influenced by PEG architecture. The polymers with the block-like configurations formed nanosized DNA complexes. In contrast, considerably higher molecular weight was necessary for the copolymer with the statistical configuration of short PEG chains to form such a small complex. Cell line-dependent influence of PEG architecture on cellular uptake, gene expression efficiency and cell viability of the polymer-DNA complexes was observed. The diblock copolymer-DNA complexes induced higher gene expression than the brush-like block copolymer-DNA complexes, and the statistical copolymer-DNA complexes mediated much lower gene expression than the block-like copolymers-DNA complexes. Increasing the molecular weight of statistical polymer to some extent improved gene expression efficiency. The statistical copolymer was less cytotoxic as compared to the block-like copolymers. These findings provide important insights into the effect of PEGylation nature on gene expression, which will be useful for the design of PEGylated gene delivery polymers.
authors.affiliation: Institute of Bioengineering and Nanotechnology, 31 Biopolis Way, Singapore 138669, Singapore.
authors.forename: Shrinivas
authors.initials: S
authors.lastname: Venkataraman
authors.forename: Wei Lin
authors.initials: WL
authors.lastname: Ong
authors.forename: Zhan Yuin
authors.initials: ZY
authors.lastname: Ong
authors.forename: Say Chye
authors.initials: SC
authors.lastname: Joachim Loo
authors.forename: Pui Lai Rachel
authors.initials: PL
authors.lastname: Ee
authors.forename: Yi Yan
authors.initials: YY
authors.lastname: Yang
mesh_terms: D002412:Cations; D016923:Cell Death; D002470:Cell Survival; D055598:Chemical Phenomena; D004247:DNA / Q000737:chemistry / Q000378:metabolism; D015870:Gene Expression; D057809:HEK293 Cells; D056945:Hep G2 Cells; D006801:Humans; D008156:Luciferases / Q000378:metabolism; D008689:Methacrylates / Q000138:chemical synthesis / Q000737:chemistry*; D046529:Microscopy, Electron, Transmission; D008970:Molecular Weight; D009757:Nylons; D011092:Polyethylene Glycols / Q000737:chemistry*; D011108:Polymers / Q000138:chemical synthesis / Q000737:chemistry*; D014162:Transfection / Q000379:methods*
chemical_list: D002412:Cations; D008689:Methacrylates; D009757:Nylons; D011108:Polymers; C407037:poly(2-(dimethylamino)ethyl methacrylate); D011092:Polyethylene Glycols; D004247:DNA; D008156:Luciferases