|Authors||Yamanouchi D, Wu J, Lazar AN, Kent KC, Chu CC, Liu B|
|Journal||Biomaterials Volume: 29 Issue: 22 Pages: 3269-77|
|Publish Date||2008 Aug|
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.