In vitro non-viral gene delivery with nanofibrous scaffolds.
Extracellular and intracellular barriers typically prevent non-viral gene vectors from having an effective transfection efficiency. Formulation of a gene delivery vehicle that can overcome the barriers is a key step for successful tissue regeneration. We have developed a novel core-shelled DNA nanoparticle by invoking solvent-induced condensation of plasmid DNA (beta-galactosidase or GFP) in a solvent mixture [94% N,N-dimethylformamide (DMF) + 6% 1x TE buffer] and subsequent encapsulation of the condensed DNA globule in a triblock copolymer, polylactide-poly(ethylene glycol)-polylactide (L8E78L8), in the same solvent environment. The polylactide shell protects the encapsulated DNA from degradation during electrospinning of a mixture of encapsulated DNA nanoparticles and biodegradable PLGA (a random copolymer of lactide and glycolide) to form a nanofibrous non-woven scaffold using the same solution mixture. The bioactive plasmid DNA can then be released in an intact form from the scaffold with a controlled release rate and transfect cells in vitro.
Liang
Dehai
D
Department of Chemistry, Stony Brook University Stony Brook, NY 11794-3400, USA.
Luu
Yen K
YK
Kim
Kwangsok
K
Hsiao
Benjamin S
BS
Hadjiargyrou
Michael
M
Chu
Benjamin
B
D000818:Animals; D002460:Cell Line; D004247:DNA / Q000008:administration & dosage* / Q000737:chemistry / Q000648:ultrastructure; D008027:Light; D049329:Nanostructures / Q000737:chemistry*; D010957:Plasmids / Q000737:chemistry; D011091:Polyesters / Q000737:chemistry*; D011092:Polyethylene Glycols / Q000737:chemistry*; D012542:Scattering, Radiation; D014162:Transfection
D011091:Polyesters; C499774:polyethylene glycol-polylactide-polyethylene glycol; D011092:Polyethylene Glycols; D004247:DNA