4.5 Article

Leukocyte-Mimetic Liposomes Penetrate Into Tumor Spheroids and Suppress Spheroid Growth by Encapsulated Doxorubicin

期刊

JOURNAL OF PHARMACEUTICAL SCIENCES
卷 110, 期 4, 页码 1701-1709

出版社

ELSEVIER SCIENCE INC
DOI: 10.1016/j.xphs.2020.10.049

关键词

Liposome; Leukocyte; Leukocyte-mimetic drug delivery system; Intermembrane protein transfer; Cancer; Tumor spheroid

资金

  1. Japan Society for the Promotion of Science (JSPS) [17H06906, 19K16336]
  2. Research Program for the Development of Intelligent Tokushima Artificial Exosome (iTEX) from Tokushima University
  3. Grants-in-Aid for Scientific Research [17H06906, 19K16336] Funding Source: KAKEN

向作者/读者索取更多资源

The study showed that leukocyte-mimetic liposomes containing leukocyte membrane proteins can effectively penetrate into tumor spheroids, inhibit tumor growth, and potentially serve as a drug delivery system for cancer treatment. Transferring leukocyte membrane proteins onto liposomes enhances their binding capacity with tumor cells, demonstrating the ability for efficient penetration into tumors.
As leukocytes can penetrate into deep regions of a tumor mass, leukocyte-mimetic liposomes (LM-Lipo) containing leukocyte membrane proteins are also expected to penetrate into tumors by exerting properties of those membrane proteins. The aim of the present study was to examine whether LM-Lipo, which were recently demonstrated to actively pass through inflamed endothelial layers, can penetrate into tumor spheroids, and to investigate the potential of LM-Lipo for use as an anticancer drug carrier. We prepared LM-Lipo via intermembrane protein transfer from human leukemia cells; transfer of leukocyte membrane proteins onto the liposomes was determined by Western blotting. LM-Lipo demonstrated a significantly high association with human lung cancer A549 cells compared with plain liposomes, which contributed to effective anti-proliferative action by encapsulated doxorubicin hydrochloride (DOX). Confocal microscopic images showed that LM-Lipo, but not plain liposomes, could efficiently penetrate into A549 tumor spheroids. Moreover, DOX-encapsulated LM-Lipo significantly suppressed tumor spheroid growth. Thus, leukocyte membrane proteins transferred onto LM-Lipo retained their unique function, which allowed for efficient penetration of the liposomes into tumor spheroids, similar to leukocytes. In conclusion, these results suggest that LM-Lipo could be a useful tumor-penetrating drug delivery system for cancer treatment. (C) 2020 American Pharmacists Association (R). Published by Elsevier Inc. All rights reserved.

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