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Synergism between a cell penetrating peptide and a pH-sensitive cationic lipid in efficient gene delivery based on double-coated nanoparticles
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| Title: | Synergism between a cell penetrating peptide and a pH-sensitive cationic lipid in efficient gene delivery based on double-coated nanoparticles |
| Authors: | Khalil, Ikramy A. Browse this author | | Kimura, Seigo Browse this author | | Sato, Yusuke Browse this author →KAKEN DB | | Harashima, Hideyoshi Browse this author →KAKEN DB |
| Keywords: | Gene delivery | | pDNA | | YSK05 | | R8 | | Nanoparticles |
| Issue Date: | 10-Apr-2018 |
| Publisher: | Elsevier |
| Journal Title: | Journal of controlled release |
| Volume: | 275 |
| Start Page: | 107 |
| End Page: | 116 |
| Publisher DOI: | 10.1016/j.jconrel.2018.02.016 |
| Abstract: | We report on the development of a highly efficient gene delivery system based on synergism between octaarginine (R8), a representative cell penetrating peptide, and YSK05, a recently developed pH-sensitive cationic lipid. Attaching a high density of R8 on the surface of YSK05 nanoparticles (NPs) that contained encapsulated plasmid DNA resulted in the formation of positively charged NPs with improved transfection efficiency. To avoid the development of a net positive charge, we controlled the density and topology of the R8 peptide through the use of a two-step coating methodology, in which the inner lipid coat was modified with a low density of R8 which was then covered with an outer neutral YSK05 lipid layer. Although used in low amounts, the R8 peptide improved cellular uptake and endosomal escape of the DNA encapsulated in YSK05 NPs, which resulted in a high transfection efficiency. The two-step coating design was essential for achieving a high degree of transfection, as evidenced by the low activity of NPs modified with the same amount of R8 in a regular single-coated design. In addition, a high transfection efficiency was not observed when R8 or YSK05 were used alone, which confirms the existence of a synergistic effect between both components. The results of this study indicate that cationic cell penetrating peptides have the ability to improve transfection activities without imparting a net positive charge when used in the proper amount and in conjunction with the appropriate design. This is expected to significantly increase the potential applications of these peptides as tools for augmenting the activity of lipid nanoparticles used in gene delivery. |
| Rights: | © 2018. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/ | | http://creativecommons.org/licenses/by-nc-nd/4.0/ |
| Type: | article (author version) |
| URI: | http://hdl.handle.net/2115/73482 |
| Appears in Collections: | 薬学研究院 (Faculty of Pharmaceutical Sciences) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)
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Submitter: Ikramy A. Khalil
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