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

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

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 nonviral vectors. Here, we show that modification of PLGA nanospheres with 3β-[N-(N0,N0-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.

Original languageEnglish
Article number0147389
JournalPloS one
Volume11
Issue number1
DOIs
Publication statusPublished - 2016 Jan 1

Fingerprint

nanospheres
Nanospheres
Therapeutic Uses
Spinal Cord Injuries
gene transfer
spinal cord
Genes
cholesterol
therapeutics
Cholesterol
Polyethyleneimine
transfection
Transfection
Rats
Polyglactin 910
Tissue regeneration
biodegradability
Neural Stem Cells
vascular endothelial growth factors
polylactic acid-polyglycolic acid copolymer

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

Cite this

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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. / Gwak, So Jung; Yun, Yeomin; Yoon, Do Heum; Kim, Keung Nyun; Ha, Yoon.

In: PloS one, Vol. 11, No. 1, 0147389, 01.01.2016.

Research output: Contribution to journalArticle

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