title: Development of Novel Drug and Gene Delivery Carriers Composed of Single-Walled Carbon Nanotubes and Designed Peptides With PEGylation.
abstract: Single-walled carbon nanotubes (SWCNTs) attract great interest in biomedical applications including drug and gene delivery. In this study, we developed a novel delivery system using SWCNTs associated with designed polycationic and amphiphilic peptides. Wrapping of SWCNTs with H-(-Lys-Trp-Lys-Gly-)7-OH [(KWKG)7] resulted in stable dispersion in water, but the composite aggregated in the buffered solution. This dispersion instability was also evident in a cell culture medium with fetal bovine serum. To improve the aqueous dispersibility, the SWCNTs-(KWKG)7 composite was further modified with polyethylene glycol (PEG) at the lysine residues via amide bond formation and the highest modification extent of 13.3% of the amino groups which corresponded to 2 PEG chains in each peptide molecule was achieved with fluorescein isothiocyanate-labeled carboxyl-PEG12. The uptake of the SWCNTs composite by A549 human lung adenocarcinoma epithelial cells was evaluated by visual observation and fluorescence activated cell sorting analysis for SWCNTs wrapped with a mixture of (KWKG)7 with PEGylation and H-(-Cys-Trp-Lys-Gly-)-OH-(KWKG)6 [CWKG(KWKG)6] labeled with fluorescent boron-dipyrromethene tetramethylrhodamine and 7-fold higher uptake comparing with SWCNTs-peptide composite without PEGylation was obtained suggesting the importance of dispersibility in addition to a cationic charge. The superior potential of SWCNTs composites assisted by polycationic and amphiphilic peptides with PEGylation was thus demonstrated.
authors.affiliation: Institute for Integrated Cell-Material Sciences, (iCeMS), Kyoto University, Kyoto 606-8302, Japan.
authors.forename: Takahisa
authors.initials: T
authors.lastname: Ohta
authors.affiliation: Institute for Integrated Cell-Material Sciences, (iCeMS), Kyoto University, Kyoto 606-8302, Japan.
authors.forename: Yasuhiko
authors.initials: Y
authors.lastname: Hashida
authors.affiliation: Department of Drug Delivery Research, Graduate School of Pharmaceutical Sciences, Kyoto University, Kyoto 606-8501, Japan.
authors.forename: Fumiyoshi
authors.initials: F
authors.lastname: Yamashita
authors.affiliation: Institute for Integrated Cell-Material Sciences, (iCeMS), Kyoto University, Kyoto 606-8302, Japan; Department of Drug Delivery Research, Graduate School of Pharmaceutical Sciences, Kyoto University, Kyoto 606-8501, Japan. Electronic address: hashidam@pharm.kyoto-u.ac.jp.
authors.forename: Mitsuru
authors.initials: M
authors.lastname: Hashida
mesh_terms: D000072283:A549 Cells; D000577:Amides / Q000737:chemistry; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004151:Dipeptides; D016503:Drug Delivery Systems; D005079:Excipients; D018014:Gene Transfer Techniques; D006801:Humans; D008239:Lysine / Q000737:chemistry; D037742:Nanotubes, Carbon / Q000737:chemistry* / Q000633:toxicity; D009842:Oligopeptides; D010455:Peptides / Q000737:chemistry* / Q000633:toxicity*; D011092:Polyethylene Glycols / Q000737:chemistry
chemical_list: D000577:Amides; D004151:Dipeptides; D005079:Excipients; D037742:Nanotubes, Carbon; D009842:Oligopeptides; D010455:Peptides; C437951:lysylglycine; C029535:lysyl-tryptophyl-alpha-lysine; D011092:Polyethylene Glycols; D008239:Lysine
keywords: carbon nanotubes; complexation; dispersion; drug delivery systems; pegylation; peptides