Tailoring charge density and hydrogen bonding of imidazolium copolymers for efficient gene delivery

Michael H. Allen, Matthew D. Green, Hiwote K. Getaneh, Kevin M. Miller, Timothy Edward Long

Research output: Contribution to journalArticle

58 Citations (Scopus)

Abstract

Conventional free radical polymerization with subsequent postpolymerization modification afforded imidazolium copolymers with controlled charge density and side chain hydroxyl number. Novel imidazolium-containing copolymers where each permanent cation contained one or two adjacent hydroxyls allowed precise structure-transfection efficiency studies. The degree of polymerization was identical for all copolymers to eliminate the influence of molecular weight on transfection efficiency. DNA binding, cytotoxicity, and in vitro gene transfection in African green monkey COS-7 cells revealed structure-property- transfection relationships for the copolymers. DNA gel shift assays indicated that higher charge densities and hydroxyl concentrations increased DNA binding. As the charge density of the copolymers increased, toxicity of the copolymers also increased; however, as hydroxyl concentration increased, cytotoxicity remained constant. Changing both charge density and hydroxyl levels in a systematic fashion revealed a dramatic influence on transfection efficiency. Dynamic light scattering of the polyplexes, which were composed of copolymer concentrations required for the highest luciferase expression, showed an intermediate DNA-copolymer binding affinity. Our studies supported the conclusion that cationic copolymer binding affinity significantly impacts overall transfection efficiency of DNA delivery vehicles, and the incorporation of hydroxyl sites offers a less toxic and effective alternative to more conventional highly charged copolymers.

Original languageEnglish
Pages (from-to)2243-2250
Number of pages8
JournalBiomacromolecules
Volume12
Issue number6
DOIs
Publication statusPublished - 2011 Jun 13
Externally publishedYes

Fingerprint

Charge density
Hydrogen bonds
Copolymers
Genes
Hydroxyl Radical
DNA
Cytotoxicity
Poisons
Dynamic light scattering
Free radical polymerization
Luciferases
Toxicity
Cations
Assays
Gels
Positive ions
Molecular weight
Polymerization

ASJC Scopus subject areas

  • Bioengineering
  • Materials Chemistry
  • Polymers and Plastics
  • Biomaterials

Cite this

Allen, M. H., Green, M. D., Getaneh, H. K., Miller, K. M., & Long, T. E. (2011). Tailoring charge density and hydrogen bonding of imidazolium copolymers for efficient gene delivery. Biomacromolecules, 12(6), 2243-2250. https://doi.org/10.1021/bm2003303

Tailoring charge density and hydrogen bonding of imidazolium copolymers for efficient gene delivery. / Allen, Michael H.; Green, Matthew D.; Getaneh, Hiwote K.; Miller, Kevin M.; Long, Timothy Edward.

In: Biomacromolecules, Vol. 12, No. 6, 13.06.2011, p. 2243-2250.

Research output: Contribution to journalArticle

Allen, MH, Green, MD, Getaneh, HK, Miller, KM & Long, TE 2011, 'Tailoring charge density and hydrogen bonding of imidazolium copolymers for efficient gene delivery', Biomacromolecules, vol. 12, no. 6, pp. 2243-2250. https://doi.org/10.1021/bm2003303
Allen, Michael H. ; Green, Matthew D. ; Getaneh, Hiwote K. ; Miller, Kevin M. ; Long, Timothy Edward. / Tailoring charge density and hydrogen bonding of imidazolium copolymers for efficient gene delivery. In: Biomacromolecules. 2011 ; Vol. 12, No. 6. pp. 2243-2250.
@article{8829aa74c91748948347a223eac67504,
title = "Tailoring charge density and hydrogen bonding of imidazolium copolymers for efficient gene delivery",
abstract = "Conventional free radical polymerization with subsequent postpolymerization modification afforded imidazolium copolymers with controlled charge density and side chain hydroxyl number. Novel imidazolium-containing copolymers where each permanent cation contained one or two adjacent hydroxyls allowed precise structure-transfection efficiency studies. The degree of polymerization was identical for all copolymers to eliminate the influence of molecular weight on transfection efficiency. DNA binding, cytotoxicity, and in vitro gene transfection in African green monkey COS-7 cells revealed structure-property- transfection relationships for the copolymers. DNA gel shift assays indicated that higher charge densities and hydroxyl concentrations increased DNA binding. As the charge density of the copolymers increased, toxicity of the copolymers also increased; however, as hydroxyl concentration increased, cytotoxicity remained constant. Changing both charge density and hydroxyl levels in a systematic fashion revealed a dramatic influence on transfection efficiency. Dynamic light scattering of the polyplexes, which were composed of copolymer concentrations required for the highest luciferase expression, showed an intermediate DNA-copolymer binding affinity. Our studies supported the conclusion that cationic copolymer binding affinity significantly impacts overall transfection efficiency of DNA delivery vehicles, and the incorporation of hydroxyl sites offers a less toxic and effective alternative to more conventional highly charged copolymers.",
author = "Allen, {Michael H.} and Green, {Matthew D.} and Getaneh, {Hiwote K.} and Miller, {Kevin M.} and Long, {Timothy Edward}",
year = "2011",
month = "6",
day = "13",
doi = "10.1021/bm2003303",
language = "English",
volume = "12",
pages = "2243--2250",
journal = "Biomacromolecules",
issn = "1525-7797",
publisher = "American Chemical Society",
number = "6",

}

TY - JOUR

T1 - Tailoring charge density and hydrogen bonding of imidazolium copolymers for efficient gene delivery

AU - Allen, Michael H.

AU - Green, Matthew D.

AU - Getaneh, Hiwote K.

AU - Miller, Kevin M.

AU - Long, Timothy Edward

PY - 2011/6/13

Y1 - 2011/6/13

N2 - Conventional free radical polymerization with subsequent postpolymerization modification afforded imidazolium copolymers with controlled charge density and side chain hydroxyl number. Novel imidazolium-containing copolymers where each permanent cation contained one or two adjacent hydroxyls allowed precise structure-transfection efficiency studies. The degree of polymerization was identical for all copolymers to eliminate the influence of molecular weight on transfection efficiency. DNA binding, cytotoxicity, and in vitro gene transfection in African green monkey COS-7 cells revealed structure-property- transfection relationships for the copolymers. DNA gel shift assays indicated that higher charge densities and hydroxyl concentrations increased DNA binding. As the charge density of the copolymers increased, toxicity of the copolymers also increased; however, as hydroxyl concentration increased, cytotoxicity remained constant. Changing both charge density and hydroxyl levels in a systematic fashion revealed a dramatic influence on transfection efficiency. Dynamic light scattering of the polyplexes, which were composed of copolymer concentrations required for the highest luciferase expression, showed an intermediate DNA-copolymer binding affinity. Our studies supported the conclusion that cationic copolymer binding affinity significantly impacts overall transfection efficiency of DNA delivery vehicles, and the incorporation of hydroxyl sites offers a less toxic and effective alternative to more conventional highly charged copolymers.

AB - Conventional free radical polymerization with subsequent postpolymerization modification afforded imidazolium copolymers with controlled charge density and side chain hydroxyl number. Novel imidazolium-containing copolymers where each permanent cation contained one or two adjacent hydroxyls allowed precise structure-transfection efficiency studies. The degree of polymerization was identical for all copolymers to eliminate the influence of molecular weight on transfection efficiency. DNA binding, cytotoxicity, and in vitro gene transfection in African green monkey COS-7 cells revealed structure-property- transfection relationships for the copolymers. DNA gel shift assays indicated that higher charge densities and hydroxyl concentrations increased DNA binding. As the charge density of the copolymers increased, toxicity of the copolymers also increased; however, as hydroxyl concentration increased, cytotoxicity remained constant. Changing both charge density and hydroxyl levels in a systematic fashion revealed a dramatic influence on transfection efficiency. Dynamic light scattering of the polyplexes, which were composed of copolymer concentrations required for the highest luciferase expression, showed an intermediate DNA-copolymer binding affinity. Our studies supported the conclusion that cationic copolymer binding affinity significantly impacts overall transfection efficiency of DNA delivery vehicles, and the incorporation of hydroxyl sites offers a less toxic and effective alternative to more conventional highly charged copolymers.

UR - http://www.scopus.com/inward/record.url?scp=79958808056&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=79958808056&partnerID=8YFLogxK

U2 - 10.1021/bm2003303

DO - 10.1021/bm2003303

M3 - Article

C2 - 21557603

AN - SCOPUS:79958808056

VL - 12

SP - 2243

EP - 2250

JO - Biomacromolecules

JF - Biomacromolecules

SN - 1525-7797

IS - 6

ER -