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Hyaluronic acid controls the uptake pathway and intracellular trafficking of an octaarginine-modified gene vector in CD44 positive- and CD44 negative-cells.
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| Title: | Hyaluronic acid controls the uptake pathway and intracellular trafficking of an octaarginine-modified gene vector in CD44 positive- and CD44 negative-cells. |
| Authors: | Yamada, Yuma Browse this author →KAKEN DB | | Hashida, Masahiro Browse this author | | Harashima, Hideyoshi Browse this author →KAKEN DB |
| Keywords: | Hyaluronan | | CD44 mediated pathway | | Cell-penetrating peptide (CCP) | | Octaarginine | | Micropinocytosis | | Intracellular trafficking | | Gene expression | | Drug delivery system | | Non-viral vector | | Liposome |
| Issue Date: | Jun-2015 |
| Publisher: | Elsevier |
| Journal Title: | Biomaterials |
| Volume: | 52 |
| Start Page: | 189 |
| End Page: | 198 |
| Publisher DOI: | 10.1016/j.biomaterials.2015.02.027 |
| PMID: | 25818425 |
| Abstract: | The cellular uptake pathway for a gene vector is an important factor in transgene expression. We previously constructed an original gene vector, multifunctional envelope-type nano device (MEND). The use of octaarginine (R8), a cell-penetrating peptide dramatically enhanced the transfection activity of the MEND since efficient cellular uptake via macropinocytosis, while the R8 should overcome its poor cell selectivity. Here we prepared an R8-MEND equipped with GALA (a peptide for endosomal escape) (R8/GALA-MEND) coated with hyaluronic acid (HA) (HA-R8/GALA-MEND), a natural ligand for cancer cells overexpressing CD44. We investigated the cellular uptake pathway of the HA-R8/GALA-MEND and the R8/GALA-MEND using HCT116 cells overexpressing CD44. Both carriers were taken up by cells mainly via macropinocytosis, whereas only the HA-R8/GALA-MEND was partially internalized into cells via a CD44-mediated pathway. Investigation of transgene expression showed that the HA-R8/GALA-MEND had a high transfection activity in HCT116 cells via both macropinocytotic and CD44-mediated pathways. On the other hand, the value for the HA-R8/GALA-MEND was significantly decreased compared with the value for the R8/GALA-MEND in NIH3T3 cells (CD44-negative cells). These findings indicate that the HA-coating controls the intracellular pathway for R8-modified nanocarriers, and that a CD44-mediated pathway is an important route for transgene expression. |
| Rights: | © 2015, Elsevier. 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/2115/66348 |
| 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: 山田 勇磨
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