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Therapeutic Use of 3β-[N-(N',N'-Dimethylaminoethane) Carbamoyl] Cholesterol-Modified PLGA Nanospheres as Gene Delivery Vehicles for Spinal Cord Injury

 So-Jung Gwak  ;  Yeomin Yun  ;  Do Heum Yoon  ;  Keung Nyun Kim  ;  Yoon Ha 
 PLOS ONE, Vol.11(1) : e0147389, 2016 
Journal Title
Issue Date
Animals ; Biological Transport ; Cholesterol/analogs & derivatives ; Cholesterol/chemistry ; Cholesterol/pharmacology ; Gene Expression ; Gene Transfer Techniques* ; Genetic Therapy/methods* ; Injections, Spinal ; Lactic Acid/chemistry ; Lactic Acid/pharmacology ; Male ; Mice ; Motor Activity ; Nanospheres/chemistry ; Neovascularization, Physiologic ; Neural Stem Cells/cytology ; Neural Stem Cells/drug effects ; Polyethyleneimine/chemistry ; Polyethyleneimine/pharmacology ; Polyglycolic Acid/chemistry ; Polyglycolic Acid/pharmacology ; Primary Cell Culture ; Rats ; Rats, Sprague-Dawley ; Recovery of Function* ; Spinal Cord/blood supply ; Spinal Cord/pathology ; Spinal Cord Injuries/genetics ; Spinal Cord Injuries/pathology ; Spinal Cord Injuries/therapy* ; Transgenes ; Vascular Endothelial Growth Factor A/genetics* ; Vascular Endothelial Growth Factor A/metabolism
Gene delivery holds therapeutic promise for the treatment of neurological diseases and spinal cord injury. Although several studies have investigated the use of non-viral vectors, such as polyethylenimine (PEI), their clinical value is limited by their cytotoxicity. Recently, biodegradable poly (lactide-co-glycolide) (PLGA) nanospheres have been explored as non-viral vectors. Here, we show that modification of PLGA nanospheres with 3β-[N-(N',N'-dimethylaminoethane) carbamoyl] cholesterol (DC-Chol) enhances gene transfection efficiency. PLGA/DC-Chol nanospheres encapsulating DNA were prepared using a double emulsion-solvent evaporation method. PLGA/DC-Chol nanospheres were less cytotoxic than PEI both in vitro and in vivo. DC-Chol modification improved the uptake of nanospheres, thereby increasing their transfection efficiency in mouse neural stem cells in vitro and rat spinal cord in vivo. Also, transgene expression induced by PLGA nanospheres was higher and longer-lasting than that induced by PEI. In a rat model of spinal cord injury, PLGA/DC-Chol nanospheres loaded with vascular endothelial growth factor gene increased angiogenesis at the injury site, improved tissue regeneration, and resulted in better recovery of locomotor function. These results suggest that DC-Chol-modified PLGA nanospheres could serve as therapeutic gene delivery vehicles for spinal cord injury.
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1. College of Medicine (의과대학) > Yonsei Biomedical Research Center (연세의생명연구원) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Neurosurgery (신경외과학교실) > 1. Journal Papers
Yonsei Authors
Gwak, So Jung(곽소정)
Kim, Keung Nyun(김긍년)
Yoon, Do Heum(윤도흠) ORCID logo https://orcid.org/0000-0003-1452-5724
Ha, Yoon(하윤)
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