Biodegradable arginine-based poly(ester-amide)s as non-viral gene delivery reagents

Dai Yamanouchi, Jun Wu, Andrew N. Lazar, K. Craig Kent, Chih Chang Chu, Bo Liu

Research output: Contribution to journalArticlepeer-review

115 Citations (Scopus)

Abstract

A novel family of synthetic biodegradable poly(ester-amide)s (Arg-PEAs) was evaluated for their biosafety and capability to transfect rat vascular smooth muscle cells, a major cell type participating in vascular diseases. Arg-PEAs showed high binding capacity toward plasmid DNA, and the binding activity was inversely correlated to the number of methylene groups in the diol segment of Arg-PEAs. All Arg-PEAs transfected smooth muscle cells with an efficiency that was comparable to the commercial transfection reagent Superfect®. However, unlike Superfect®, Arg-PEAs, over a wide range of dosages, had minimal adverse effects on cell morphology, viability or apoptosis. Using rhodamine-labeled plasmid DNA, we demonstrated that Arg-PEAs were able to deliver DNA into nearly 100% of cells under optimal polymer-to-DNA weight ratios, and that such a high level of delivery was achieved through an active endocytosis mechanism. A large portion of DNA delivered, however, was trapped in acidic endocytotic compartments, and subsequently was not expressed. These results suggest that with further modification to enhance their endosome escape, Arg-PEAs can be attractive candidates for non-viral gene carriers owning to their high cellular uptake nature and reliable cellular biocompatibility.

Original languageEnglish
Pages (from-to)3269-3277
Number of pages9
JournalBiomaterials
Volume29
Issue number22
DOIs
Publication statusPublished - 08-2008
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Biophysics
  • Bioengineering
  • Ceramics and Composites
  • Biomaterials
  • Mechanics of Materials

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