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

Yuma Yamada, Reina Munechika, Satrialdi, Fumika Kubota, Yusuke Sato, Yu Sakurai, Hideyoshi Harashima

Research output: Contribution to journalArticlepeer-review

5 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)2493-2500
Number of pages8
JournalJournal of Pharmaceutical Sciences
Volume109
Issue number8
DOIs
Publication statusPublished - 2020 Aug
Externally publishedYes

Keywords

  • Drug-resistant cancer
  • In vivo delivery
  • Liposomes
  • MITO-Porter
  • Mitochondria
  • Mitochondrial delivery

ASJC Scopus subject areas

  • Pharmaceutical Science

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