期刊
JOURNAL OF PHARMACEUTICAL SCIENCES
卷 109, 期 8, 页码 2493-2500出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.xphs.2020.04.020
关键词
Mitochondria; Drug-resistant cancer; Liposomes; Mitochondrial delivery; In vivo delivery; MITO-Porter
资金
- Ministry of Education, Culture, Sports, Science and Technology, the Japanese Government (MEXT) [17H02094]
- Special Education and Research Expenses of the MEXT
- Kobayashi Foundation for Cancer Research
- Terumo Life Science Foundation
- Indonesia Endowment Fund for Education (LPDP), Ministry of Finance of the Republic of Indonesia
- Ministry of Research, Technology, and Higher Education of the Republic of Indonesia
- Grants-in-Aid for Scientific Research [17H02094] Funding Source: KAKEN
Mitochondrial delivery of an anticancer drug targeting cancer cells would eventually result in cell death. To achieve this, a drug delivery system targeting mitochondria is needed. We recently developed a MITOPorter, a liposome that delivers its cargo to mitochondria. We reported that such a MITO-Porter could deliver doxorubicin (DOX), an anticancer drug, to mitochondria in OS-RC-2 cells, a drug resistant cancer cell, resulting in inhibiting the cell growth, based in in vitro experiments. Herein, we report on validating the benefit of such a therapeutic strategy for treating drug resistant cancers by the in vivo targeting of mitochondria. We prepared a DOX-MITO-Porter, in which DOX was encapsulated in the MITO-Porter and optimized its retention in blood circulation. When the DOX-MITO-Porter was administered to mice bearing OS-RC-2 cells via tail vein injection, tumor size was significantly decreased, compared to DOX itself and to the DOX-encapsulated polyethylene glycol-modified liposome (DOX-PEG-LP). Intracellular observation confirmed that the DOX-MITO-Porter had accumulated in tumor mitochondria. It was also found a relationship between anti-tumor effect and the mitochondrial function, as indicated by the depolarization of mitochondrial membrane potential. This study provides support for the utility of an in vivo mitochondrial delivery system in drug resistant cancer therapies. (c) 2020 American Pharmacists Association (R). Published by Elsevier Inc. All rights reserved.
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