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Synergistic Enhancement of Cellular Uptake With CD44-Expressing Malignant Pleural Mesothelioma by Combining Cationic Liposome and Hyaluronic Acid-Lipid Conjugate
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Title: | Synergistic Enhancement of Cellular Uptake With CD44-Expressing Malignant Pleural Mesothelioma by Combining Cationic Liposome and Hyaluronic Acid-Lipid Conjugate |
Authors: | Sakurai, Yu Browse this author | Kato, Akari Browse this author | Hida, Yasuhiro Browse this author | Hamada, Junichi Browse this author | Maishi, Nako Browse this author | Hida, Kyoko Browse this author | Harashima, Hideyoshi Browse this author →KAKEN DB |
Keywords: | lipid nanoparticle | hyaluronan | CD44 | malignant pleural mesothelioma |
Issue Date: | Oct-2019 |
Publisher: | Elsevier |
Journal Title: | Journal of Pharmaceutical Sciences |
Volume: | 108 |
Issue: | 10 |
Start Page: | 3218 |
End Page: | 3224 |
Publisher DOI: | 10.1016/j.xphs.2019.06.012 |
Abstract: | Malignant pleural mesothelioma (MPM) is a highly aggressive form of cancer, with a median survival of less than 1 year. It is well known that the hyaluronan (HA) receptor CD44 is highly expressed by MPM cells and is reported to be correlated with a poor prognosis. We herein report on the development of a new type if drug delivery system against CD44 that involves the use of lipid nanoparticles (LNPs) equipped with a new type of HA derivative. In this study, we evaluated HA-lipid conjugation (HAL) via the end of the HA molecule through reductive amination, a process that allowed the carboxylate group to remain intact. As a result, the HAL-modified LNP appears to be a potent nanoparticle for dealing with MPM. Surprisingly, the use of a combination of a cationic lipid and HAL had a synergistic effect on cellular uptake in MPM and consequently permitted an anti-cancer drug such as cis-diamminedichloro-platinum(II) (CDDP). Intrapleural injection of CDDP-loaded HAL-LNP (1.5 mg/kg as CDDP) per week significantly suppressed the progression of this type of cancer in an MPM orthotopic model. These results suggest that HAL-modified LNP represents a potent delivery system for MPM cells that express high levels of CD44. (c) 2019 American Pharmacists Association (R). Published by Elsevier Inc. All rights reserved. |
Rights: | ©2019. 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/2115/79675 |
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: 原島 秀吉
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