Polyplexes Assembled with Internally Quaternized PAMAM-OH Dendrimer and Plasmid DNA Have a Neutral Surface and Gene Delivery Potency

Interior tertiary amine groups of PAMAM-OH dendrimers (hydroxyl-terminated polyamidoamine, PAMAM) were modified by methylation to make these polymers have a more cationic character, which enabled electrostatic interaction between PAMAM-OH and plasmid DNA. A methylation reaction was dose-dependent, p...

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Bibliographic Details
Published in:Bioconjugate chemistry 2003-11, Vol.14 (6), p.1214-1221
Main Authors: Lee, Jung Hoon, Lim, Yong-beom, Choi, Joon Sig, Lee, Yan, Kim, Tae-il, Kim, Hyun Jin, Yoon, Jae Keun, Kim, Kwan, Park, Jong-sang
Format: Article
Language:English
Subjects:
Cell Line
Cell Membrane - metabolism
Dendrimers
DNA - metabolism
Ethidium - chemistry
Gene Transfer Techniques
Genetic Vectors
Humans
Light
Methylation
Microscopy, Atomic Force
Molecular Structure
Plasmids - metabolism
Polyamines - chemical synthesis
Polyamines - metabolism
Polyamines - toxicity
Scattering, Radiation
Surface Properties
Transfection
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Summary:Interior tertiary amine groups of PAMAM-OH dendrimers (hydroxyl-terminated polyamidoamine, PAMAM) were modified by methylation to make these polymers have a more cationic character, which enabled electrostatic interaction between PAMAM-OH and plasmid DNA. A methylation reaction was dose-dependent, producing internally quaternized PAMAM-OH (QPAMAM-OH), thereby making tertiary amine/quaternary amine ratio adjustment possible. More highly condensed particles of plasmid DNA were formed as the degree of quaternization increased, whereas unmodified polymer (PAMAM-OH) could not. The location of positive charges in the internal position of QPAMAM-OH resulted in the formation of neutral polyplexes in which ζ potential leveled off near the zero value even at high charge ratios (+/−) of 10. A light scattering experiment showed that the polyplex formed by QPAMAM-OH was very small with the size of 53.3 nm at the optimum condition. QPAMAM-OH/DNA polyplexes were round-shaped with the more compact and small particles formed as the charge ratio increased. QPAMAM-OH showed much reduced cytotoxicity compared with starburst PAMAM and branched polyethyleneimine (PEI) in which shielding of interior positive charges by surface hydroxyls might be the reason for this favorable result. These results suggest that QPAMAM-OH could be a promising tool as a nonviral vector both by itself and in conjugated form with targeting ligands.
ISSN:1043-1802
1520-4812
DOI:10.1021/bc034095g