Synergistic Enhancement of Cellular Uptake With CD44-Expressing Malignant Pleural Mesothelioma by Combining Cationic Liposome and Hyaluronic Acid–Lipid Conjugate

Yu Sakurai, Akari Kato, Yasuhiro Hida, Junichi Hamada, Nako Maishi, Kyoko Hida, Hideyoshi Harashima

Research output: Contribution to journalArticlepeer-review

5 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)3218-3224
Number of pages7
JournalJournal of Pharmaceutical Sciences
Volume108
Issue number10
DOIs
Publication statusPublished - 2019 Oct
Externally publishedYes

Keywords

  • CD44
  • hyaluronan
  • lipid nanoparticle
  • malignant pleural mesothelioma

ASJC Scopus subject areas

  • Pharmaceutical Science

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