Influence of TAT-peptide polymerization on properties and transfection activity of TAT/DNA polyplexes

Devika Soundara Manickam, Harender S. Bisht, Lei Wan, Guangzhao Mao, David Oupicky

Research output: Contribution to journalArticlepeer-review

86 Scopus citations

Abstract

Use of bioactive cationic peptides as gene carriers is limited by instability of their DNA complexes in vivo and by the loss of their biological activity due to undesired interactions of their bioactive parts with the DNA. To overcome the two major limitations, biodegradable high-molecular-weight form of TAT peptide (POLYTAT) sensitive to cellular redox-potential gradients was synthesized in this study by oxidative polycondensation. Physicochemical and transfection properties of DNA polyplexes based on POLYTAT were investigated and compared with polyplexes based on TAT polymer prepared by in situ template-assisted polymerization. Physicochemical properties of TAT-based polyplexes were affected by the molecular weight and method of polymerization of the TAT peptide. All TAT-based DNA polyplexes exhibited reduced cytotoxicity when compared with control polyethylenimine (PEI) polyplexes. Polyplexes based on both high-molecular-weight TAT polypeptides exhibited increased transfection efficiency compared to control TAT peptide but lower than that of PEI polyplexes. The evidence shows that transfection activity of TAT-based polyplexes is strongly dependent on the presence of chloroquine and therefore suggests that TAT polyplexes are internalized by an endocytosis. Overall, high-molecular-weight reducible polycations based on bioactive peptides has the potential as versatile carriers of nucleic acids that display low cytotoxicity and can prove to be especially beneficial in cases that require surface presentation of membrane-active or cell-specific targeting peptides.

Original languageEnglish (US)
Pages (from-to)293-306
Number of pages14
JournalJournal of Controlled Release
Volume102
Issue number1
DOIs
StatePublished - Jan 20 2005
Externally publishedYes

Keywords

  • Polypeptide
  • Polyplex
  • TAT
  • Toxicity
  • Transfection

ASJC Scopus subject areas

  • Pharmaceutical Science

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