pDNA bioparticles: Comparative heterogeneity, surface, binding, and activity analyses

P. Medberry, Dennis M Styne, T. Van Hecke, R. K. DeLong

Research output: Contribution to journalArticle

17 Scopus citations

Abstract

New applications for nucleic acid-bound micro/nanoparticles are emerging in drug delivery, biocatalysis, diagnostics, and toxicology. Bioactivity of viral or liposomal based technologies is limited by heterogeneity, partitioning, aggregation, and protein binding in physiological fluids, underlying immunotoxicity, and poor in vitro and cell-culture corollaries. Here we have systematically investigated novel pDNA bioparticles formed through complexation to model non-viral/non-lipid materials, peptides, aminoglycans, and small molecules (polybrene, chitosan, butirosin, protamine, Lys10, RGDS, bupivacaine, and chlorpromazine). On the basis of characterization by heterogeneity, kinetics, partitioning in physiological fluid and serum protein-binding, surface, size and electrophoretic behavior, transfection, and immunotoxicity, notably protamine, and chitosan DNA particles gave a long lifetime (12-18h), low protein-binding (<10μg/ml), good transfection activity (10 2-104RLU/mg cell protein), and low immunotoxicity. Our results support further evaluation of these materials as potential alternatives to viral or liposomal approaches, in combination with pDNA as binding, expression or therapeutic agents.

Original languageEnglish (US)
Pages (from-to)426-432
Number of pages7
JournalBiochemical and Biophysical Research Communications
Volume319
Issue number2
DOIs
StatePublished - Jun 25 2004

Keywords

  • Bioparticles
  • Characterization
  • Expression
  • Gene delivery
  • Immunotoxicity
  • Plasmid DNA

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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