Development of Novel Drug and Gene Delivery Carriers Composed of Single- Walled Carbon Nanotubes and Designed Peptides With PEGylation

作者：Ohta Takahisa; Hashida Yasuhiko; Yamashita Fumiyoshi; Hashida Mitsuru^*

来源：Journal of Pharmaceutical Sciences, 2016, 105(9): 2815-2824.

DOI：10.1016/j.xphs.2016.03.031

• carbon nanotubes
• peptides
• pegylation
• complexation
• dispersion
• drug delivery systems

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 isothiocyanateelabeled 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.

• 出版日期2016-9