Poly(beta-amino ester) and cationic phospholipid-based lipopolyplexes for gene delivery and transfection in human aortic endothelial and smooth muscle cells.
Safe and effective nonviral gene delivery and transfection in primary human vascular endothelial cells (EC) and smooth muscle cells (SMC) has tremendous potential for cardiovascular diseases such as in the treatment of coronary restenosis. Using a combination of a cationic biodegradable polymer, poly(beta-amino ester) (PBAE), and a cationic phospholipid, 1,2-dioleoyl-3-trimethylammonium propane (DOTAP), we have engineered a lipopolyplex nanovector system that can transfect EC and SMC cells with reasonably high efficiency. For instance, upon addition of 1.0 microg DNA complexed in lipopolyplexes the transfection efficiency in SMC was 20% and in EC was 33%. The results of this study shows that PBAE-DOTAP-plasmid DNA lipopolyplexes are a promising nonviral vector system for gene delivery and transfection in EC and SMC.
Brito
Luis
L
Department of Pharmaceutical Sciences, Northeastern University, Boston, Massachusetts 02115, USA.
Little
Steven
S
Langer
Robert
R
Amiji
Mansoor
M
D001011:Aorta / Q000166:cytology; D001672:Biocompatible Materials / Q000138:chemical synthesis* / Q000378:metabolism; D049109:Cell Proliferation; D002478:Cells, Cultured; D004247:DNA / Q000378:metabolism*; D004587:Electrophoresis, Agar Gel; D004730:Endothelium, Vascular / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D004952:Esters / Q000737:chemistry* / Q000378:metabolism; D005229:Fatty Acids, Monounsaturated / Q000737:chemistry* / Q000378:metabolism; D005434:Flow Cytometry; D005456:Fluorescent Dyes / Q000737:chemistry / Q000378:metabolism; D049452:Green Fluorescent Proteins / Q000378:metabolism; D006801:Humans; D008856:Microscopy, Fluorescence; D032389:Myocytes, Smooth Muscle / Q000378:metabolism*; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D010957:Plasmids / Q000008:administration & dosage; D011108:Polymers / Q000737:chemistry* / Q000378:metabolism; D000644:Quaternary Ammonium Compounds / Q000737:chemistry* / Q000378:metabolism; D014162:Transfection / Q000379:methods*
D001672:Biocompatible Materials; D004952:Esters; D005229:Fatty Acids, Monounsaturated; D005456:Fluorescent Dyes; D011108:Polymers; D000644:Quaternary Ammonium Compounds; C485184:enhanced green fluorescent protein; C507253:poly(beta-amino ester); D049452:Green Fluorescent Proteins; D004247:DNA; D052250:Nitric Oxide Synthase Type III; C070046:1,2-dioleoyloxy-3-(trimethylammonium)propane