Effect of albumin and polyanion on the structure of DNA complexes with polycation containing hydrophilic nonionic block

David Oupicky, Čestmír Koňák, Philip R. Dash, Leonard W. Seymour, Karel Ulbrich

Research output: Contribution to journalArticle

89 Citations (Scopus)

Abstract

Self-assembling systems based on ionic complexes of DNA with block copolymer of N-(2-hydroxypropyl)methacrylamide with 2-(trimethylammonio)ethyl methacrylate were studied as systems suitable for gene delivery. In this study, the influence of albumin and polyanion on parameters of the DNA polyelectrolyte complexes in aqueous solutions was investigated. Static and dynamic light-scattering methods were used as a main tool for characterizing these interactions. It was found that albumin is not able to release free DNA, but it can rather bind to the complexes forming ternary DNA-polycation-albumin complexes with increased hydrodynamic radii of about 10 nm. Polyanion tested, sodium poly(styrenesulfonate), was able to release free DNA in the presence of a low-molecular-weight electrolyte. In the absence of a low-molecular-weight electrolyte, only formation of ternary complexes and no DNA release was observed. The in vivo biodistribution analysis of DNA complexes showed no effect of the presence of hydrophilic nonionic poly(HPMA) on the circulatory time or organ distribution. The interaction of DNA complexes with albumin and other plasma proteins was suggested to be a major reason for the short circulatory times.

Original languageEnglish (US)
Pages (from-to)764-772
Number of pages9
JournalBioconjugate Chemistry
Volume10
Issue number5
DOIs
StatePublished - Sep 1 1999

Fingerprint

Albumins
DNA
hydroxypropyl methacrylate
Electrolytes
Molecular Weight
Molecular weight
Gene Transfer Techniques
polycations
polyanions
Beam plasma interactions
Dynamic light scattering
Hydrodynamics
Polyelectrolytes
Block copolymers
Blood Proteins
Genes
Sodium
Proteins
Plasmas

ASJC Scopus subject areas

  • Biotechnology
  • Bioengineering
  • Biomedical Engineering
  • Pharmacology
  • Pharmaceutical Science
  • Organic Chemistry

Cite this

Effect of albumin and polyanion on the structure of DNA complexes with polycation containing hydrophilic nonionic block. / Oupicky, David; Koňák, Čestmír; Dash, Philip R.; Seymour, Leonard W.; Ulbrich, Karel.

In: Bioconjugate Chemistry, Vol. 10, No. 5, 01.09.1999, p. 764-772.

Research output: Contribution to journalArticle

Oupicky, David ; Koňák, Čestmír ; Dash, Philip R. ; Seymour, Leonard W. ; Ulbrich, Karel. / Effect of albumin and polyanion on the structure of DNA complexes with polycation containing hydrophilic nonionic block. In: Bioconjugate Chemistry. 1999 ; Vol. 10, No. 5. pp. 764-772.
@article{4da93c8efc7641cb831c38ce5c8a054d,
title = "Effect of albumin and polyanion on the structure of DNA complexes with polycation containing hydrophilic nonionic block",
abstract = "Self-assembling systems based on ionic complexes of DNA with block copolymer of N-(2-hydroxypropyl)methacrylamide with 2-(trimethylammonio)ethyl methacrylate were studied as systems suitable for gene delivery. In this study, the influence of albumin and polyanion on parameters of the DNA polyelectrolyte complexes in aqueous solutions was investigated. Static and dynamic light-scattering methods were used as a main tool for characterizing these interactions. It was found that albumin is not able to release free DNA, but it can rather bind to the complexes forming ternary DNA-polycation-albumin complexes with increased hydrodynamic radii of about 10 nm. Polyanion tested, sodium poly(styrenesulfonate), was able to release free DNA in the presence of a low-molecular-weight electrolyte. In the absence of a low-molecular-weight electrolyte, only formation of ternary complexes and no DNA release was observed. The in vivo biodistribution analysis of DNA complexes showed no effect of the presence of hydrophilic nonionic poly(HPMA) on the circulatory time or organ distribution. The interaction of DNA complexes with albumin and other plasma proteins was suggested to be a major reason for the short circulatory times.",
author = "David Oupicky and Čestm{\'i}r Koň{\'a}k and Dash, {Philip R.} and Seymour, {Leonard W.} and Karel Ulbrich",
year = "1999",
month = "9",
day = "1",
doi = "10.1021/bc990007+",
language = "English (US)",
volume = "10",
pages = "764--772",
journal = "Bioconjugate Chemistry",
issn = "1043-1802",
publisher = "American Chemical Society",
number = "5",

}

TY - JOUR

T1 - Effect of albumin and polyanion on the structure of DNA complexes with polycation containing hydrophilic nonionic block

AU - Oupicky, David

AU - Koňák, Čestmír

AU - Dash, Philip R.

AU - Seymour, Leonard W.

AU - Ulbrich, Karel

PY - 1999/9/1

Y1 - 1999/9/1

N2 - Self-assembling systems based on ionic complexes of DNA with block copolymer of N-(2-hydroxypropyl)methacrylamide with 2-(trimethylammonio)ethyl methacrylate were studied as systems suitable for gene delivery. In this study, the influence of albumin and polyanion on parameters of the DNA polyelectrolyte complexes in aqueous solutions was investigated. Static and dynamic light-scattering methods were used as a main tool for characterizing these interactions. It was found that albumin is not able to release free DNA, but it can rather bind to the complexes forming ternary DNA-polycation-albumin complexes with increased hydrodynamic radii of about 10 nm. Polyanion tested, sodium poly(styrenesulfonate), was able to release free DNA in the presence of a low-molecular-weight electrolyte. In the absence of a low-molecular-weight electrolyte, only formation of ternary complexes and no DNA release was observed. The in vivo biodistribution analysis of DNA complexes showed no effect of the presence of hydrophilic nonionic poly(HPMA) on the circulatory time or organ distribution. The interaction of DNA complexes with albumin and other plasma proteins was suggested to be a major reason for the short circulatory times.

AB - Self-assembling systems based on ionic complexes of DNA with block copolymer of N-(2-hydroxypropyl)methacrylamide with 2-(trimethylammonio)ethyl methacrylate were studied as systems suitable for gene delivery. In this study, the influence of albumin and polyanion on parameters of the DNA polyelectrolyte complexes in aqueous solutions was investigated. Static and dynamic light-scattering methods were used as a main tool for characterizing these interactions. It was found that albumin is not able to release free DNA, but it can rather bind to the complexes forming ternary DNA-polycation-albumin complexes with increased hydrodynamic radii of about 10 nm. Polyanion tested, sodium poly(styrenesulfonate), was able to release free DNA in the presence of a low-molecular-weight electrolyte. In the absence of a low-molecular-weight electrolyte, only formation of ternary complexes and no DNA release was observed. The in vivo biodistribution analysis of DNA complexes showed no effect of the presence of hydrophilic nonionic poly(HPMA) on the circulatory time or organ distribution. The interaction of DNA complexes with albumin and other plasma proteins was suggested to be a major reason for the short circulatory times.

UR - http://www.scopus.com/inward/record.url?scp=0344378203&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0344378203&partnerID=8YFLogxK

U2 - 10.1021/bc990007+

DO - 10.1021/bc990007+

M3 - Article

VL - 10

SP - 764

EP - 772

JO - Bioconjugate Chemistry

JF - Bioconjugate Chemistry

SN - 1043-1802

IS - 5

ER -