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Poly(L-lactide-co-glycolide) nanospheres conjugated with a nuclear localization signal for delivery of plasmid DNA

Cited 41 time in Web of Science Cited 44 time in Scopus
Authors

Jeon, Oju; Lim, Hee-Won; Lee, Minhyung; Song, Su Jin; Kim, Byung-Soo

Issue Date
2007-04
Publisher
TAYLOR & FRANCIS LTD
Citation
JOURNAL OF DRUG TARGETING, Vol.15 No.3, pp.190-198
Abstract
Polymeric nanospheres fabricated from biodegradable poly(lactide-co-glycolide) ( PLGA) have been extensively investigated for applications in gene delivery. In this study, we show that the covalent conjugation of a nuclear localization signal ( NLS, SV40 peptide) on PLGA nanospheres enhances the gene transfection efficiency. NLS conjugated PLGA copolymer was prepared by using a coupling reaction between maleimide- terminated PLGA copolymer and NLS in the presence of Imject maleimide conjugation buffer. PLGA nanospheres encapsulating plasmid ( pDNA) were prepared by using a double emulsion-solvent evaporation method. The kinetics of in vitro release of pDNA from PLGA nanospheres was determined with UV in phosphate buffered saline ( PBS). Gene transfection efficiency in human dermal fibroblasts was tested in vitro using nanospheres encapsulating the luciferase gene. The conjugation of the NLS peptide to the PLGA nanospheres could improve the nuclear localization and/ or cellular uptake of PLGA nanosphere/ pDNA constructs and thereby improve the transfection efficiency of a PLGA nanosphere gene delivery system. The pDNA was released from PLGA nanospheres over nine days. NLS conjugation enhanced the gene transfection efficiency in vitro by 1.2 similar to 3.2- fold over 13 days. PLGA/ pDNA nanospheres appeared to be superior to PEI/ pDNA complexes for the long- term expression of pDNA. Furthermore, the level of the sustained gene expression of the PLGA nanospheres was enhanced by the conjugation of NLS to the PLGA nanospheres. This study showed that the NLS conjugation enhanced the gene transfection efficiency of the PLGA nanosphere gene delivery system in vitro and that the enhanced gene expression was sustained for at least 13 days.
ISSN
1061-186X
URI
https://hdl.handle.net/10371/204390
DOI
https://doi.org/10.1080/10611860601143479
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  • College of Engineering
  • School of Chemical and Biological Engineering
Research Area biomaterials, nanomedicine, regenerative medicine

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