In Vitro Cellular Gene Delivery Employing a Novel Composite Material of Single-Walled Carbon Nanotubes Associated With Designed Peptides With Pegylation
| Autor: | Takahisa Ohta, Fumiyoshi Yamashita, Yasuhiko Hashida, Yuriko Higuchi, Mitsuru Hashida |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Pharmaceutical Science 02 engineering and technology Polyethylene glycol Gene delivery Polyethylene Glycols 03 medical and health sciences chemistry.chemical_compound Amphiphile PEG ratio Humans Organic chemistry Electrophoresis Gel Two-Dimensional Nanotubes Carbon Gene Transfer Techniques 021001 nanoscience & nanotechnology Peptide Fragments 030104 developmental biology Monomer chemistry A549 Cells Drug delivery Dispersion stability PEGylation Biophysics 0210 nano-technology |
| Zdroj: | Journal of Pharmaceutical Sciences. 106:792-802 |
| ISSN: | 0022-3549 |
| DOI: | 10.1016/j.xphs.2016.10.025 |
| Popis: | Single-walled carbon nanotubes (SWCNTs) attract great interest in biomedical fields including application for drug delivery system. In this study, we developed a novel gene delivery system employing SWCNTs associated with polycationic and amphiphilic H-(-Lys-Trp-Lys-Gly-)7-OH [(KWKG)7] peptides having pegylation. SWCNTs wrapped with (KWKG)7 formed a complex with plasmid DNA (pDNA) in aqueous solution based on polyionic interaction but later underwent aggregation. On the other hand, a complex of pDNA and SWCNT-(KWKG)7 modified with polyethylene glycol (PEG) chains of 12 units [SWCNT-(KWKG)7-(PEG)12] afforded good dispersion stability for 24 h even in a cell culture medium. The in vitro cellular uptake of SWCNT-(KWKG)7-(PEG)12/pDNA complex prepared with fluorescence-labeled pDNA was evaluated with fluorescent microscopic observation and flow cytometry. The uptake by A549 human lung adenocarcinoma epithelial cells increased along with the extent of pegylation, suggesting the importance of dispersion stability in addition to the cationic charge which facilitates ionic cellular interaction. The expression of pDNA encoding the monomeric Kusabira-Orange 2 fluorescent protein in the form of the SWCNT-(KWKG)7-(PEG)12/pDNA complex demonstrated remarkable enhancement of transfection depending also on the extent of pegylation and the N/P ratio. The potential of the SWCNT composite wrapped with polycationic and amphiphilic (KWKG)7 with pegylation as a carrier for gene delivery was demonstrated. |
| Databáze: | OpenAIRE |
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