Biodegradable arginine-based poly(ester-amide)s as non-viral gene delivery reagents.
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.
Yamanouchi
Dai
D
Division of Vascular Surgery, Department of Surgery, Weill Medical College of Cornell University, New York, NY 10021, USA.
Wu
Jun
J
Lazar
Andrew N
AN
Kent
K Craig
KC
Chu
Chih-Chang
CC
Liu
Bo
B
D000818:Animals; D001120:Arginine / Q000737:chemistry*; D001672:Biocompatible Materials / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D002470:Cell Survival / Q000187:drug effects; D004247:DNA / Q000737:chemistry / Q000235:genetics; D005822:Genetic Vectors / Q000737:chemistry* / Q000235:genetics; D011073:Polyamines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D011091:Polyesters / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D051381:Rats; D014162:Transfection / Q000379:methods
D001672:Biocompatible Materials; D011073:Polyamines; D011091:Polyesters; D004247:DNA; D001120:Arginine