Mitochondrial Delivery of an Anticancer Drug Via Systemic Administration Using a Mitochondrial Delivery System That Inhibits the Growth of Drug-Resistant Cancer Engrafted on Mice
Autor: | Yuma Yamada, Yusuke Sato, Yu Sakurai, Reina Munechika, Hideyoshi Harashima, Fumika Kubota, Satrialdi |
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Rok vydání: | 2019 |
Předmět: |
Pharmaceutical Science
Antineoplastic Agents 02 engineering and technology Drug resistance Mitochondrion Pharmacology Administration Cutaneous 030226 pharmacology & pharmacy 03 medical and health sciences Mice 0302 clinical medicine Drug Delivery Systems Neoplasms polycyclic compounds medicine Animals Doxorubicin Liposome Cell growth Chemistry technology industry and agriculture 021001 nanoscience & nanotechnology Mitochondria Cancer cell Drug delivery Liposomes Systemic administration 0210 nano-technology medicine.drug |
Zdroj: | Journal of pharmaceutical sciences. 109(8) |
ISSN: | 1520-6017 |
Popis: | 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 MITO-Porter, 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. |
Databáze: | OpenAIRE |
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