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Effects of trehalose click polymer length on pDNA complex stability and delivery efficacy

Paper ID Volume ID Publish Year Pages File Format Full-Text
9995 657 2007 14 PDF Available
Title
Effects of trehalose click polymer length on pDNA complex stability and delivery efficacy
Abstract

Cationic polymers are currently being studied as non-viral vectors to deliver therapeutic DNA into cells. In this study, a series of trehalose-based glycopolymers containing four secondary amines in the repeat unit were synthesized via the ‘click reaction’ [degrees of polymerization (nw)=35, 53, 75, or 100] to elucidate how the polymer length affects the bioactivity. The four structures bound and charge-neutralized pDNA with similar affinity that was independent of the length, as determined through gel electrophoresis, heparin competitive displacement, and isothermal titration calorimetric assays. Dynamic light scattering measurements revealed that the polyplexes formed with the longer polymers (nw=53, 75, or 100) inhibited flocculation in media containing serum, whereas the polyplexes formed with the shorter polymer (nw=35) aggregated rapidly. Similar results were observed via transmission electron microscopy studies, where the nanoparticles formed with the polymers having longer degrees of polymerization showed discrete particles in media containing 10% serum. Transfection experiments revealed that the polymers exhibited low cytotoxicity at low N/P ratios and could facilitate high cellular uptake and gene expression in HeLa and H9c2(2-1) cells, and the results were dependent on the degrees of polymerization (longer polymers yielded higher transfection and toxicity).

Keywords
Bioactivity; Copolymer; DNA; Gene transfer; Polymerization; In vitro
First Page Preview
Effects of trehalose click polymer length on pDNA complex stability and delivery efficacy
Publisher
Database: Elsevier - ScienceDirect
Journal: Biomaterials - Volume 28, Issue 18, 2007, Pages 2885–2898
Authors
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Subjects
Physical Sciences and Engineering Chemical Engineering Bioengineering