NDLI: Amino poly(glycerol methacrylate)s for oligonucleic acid delivery with enhanced transfection efficiency and low cytotoxicity

Content Provider	Royal Society of Chemistry (RSC)
Author	Yang, Yingwei Wang, Yinong Ma, Jianbiao Ma, Yanan Gao, Hui Wu, Guolin Fan, Yunge Lu, Xueyou Li, Jianfa
Copyright Year	2011
Abstract	To improve the transfection activity and reduce cell cytotoxicity of polycations with antisense oligonucleotide (AON), poly(glycidyl methacrylate)s (PGMAs) were modified with different amines, i.e., methylethylamine (MEA), 2-amino-1-butanol (2-ABO) and 4-amino-1-butanol (4-ABO). The structures of resulting polymers were well characterized and their thermal properties were studied by differential scanning calorimetry (DSC). The amino PGMA could self-assemble with AON in a Tris buffer solution, resulting in narrowly distributed polymer/AON complexes with a size of 0.1–0.3 μm at an amine-group-of-polymer/phosphate-group-of-nucleotide ratio (N/P ratio) of 0.5–3. Spherical nanoparticles of the complexes were visualized using atomic force microscopy (AFM), and the gel electrophoresis and zeta potential assay evidenced the formation of complexes at relatively low N/P ratios. Stability of the complexes towards dissociation was tested using ethidium bromide displacement assay. Protection of the incorporated AON against DNase I degradation was also evaluated. An increased charge ratio and a synergistic effect of hydrogen bonding in this system contributed to the increased stability of the complex, which prevents the incorporated AON from nuclease degradation. In vitro cytotoxicity experiments on COS-7 cells showed that all amino PGMAs displayed lower toxicity compared to the control PEI25k, except for the polymers with a relatively high molecular weight (30 kDa). In addition, the MEA modified linear and star-shaped PGMA (Mn in the range of 15–20 kDa) as well as 4-ABO modified linear PGMA complexes exhibited higher transfection efficiencies in vitro, compared to PEI25k. These results demonstrated that amino PGMAs with suitable amine groups and molecular weight can be used as safe and efficient AON delivery polymers.
Starting Page	9239
Ending Page	9247
Page Count	9
File Format	HTM / HTML PDF
ISSN	1744683X
Volume Number	7
Issue Number	19
Journal	Soft Matter
DOI	10.1039/c1sm05756a
Language	English
Publisher	Royal Society of Chemistry
Access Restriction	Open
Subject Keyword	AON Ethanolamine Differential scanning calorimetry Gel electrophoresis Cytotoxicity Polymer Dissociative Buffer solution Transfection Ethidium bromide Deoxyribonuclease I Atomic-force microscopy DSC Zeta potential Micrometre Butanol Oligonucleotide Glycidyl methacrylate Nuclease Hydrogen bond
Content Type	Text
Resource Type	Article
Subject	Chemistry Condensed Matter Physics

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