Mitochondrial Delivery of Doxorubicin Using MITO-Porter Kills Drug-Resistant Renal Cancer Cells via Mitochondrial Toxicity

Yuma Yamada, Reina Munechika, Eriko Kawamura, Yu Sakurai, Yusuke Sato, Hideyoshi Harashima

Research output: Contribution to journalArticlepeer-review

14 Citations (Scopus)

Abstract

Most anticancer drugs are intended to function in the nuclei of cancer cells. If an anticancer drug could be delivered to mitochondria, the source of cellular energy, this organelle would be destroyed, resulting in the arrest of the energy supply and the killing of the cancer cells. To achieve such an innovative strategy, a mitochondrial drug delivery system targeted to cancer cells will be required. We recently reported on the development of a MITO-Porter, a liposome for mitochondrial delivery. In this study, we validated the utility of such a cancer therapeutic strategy by delivering anticancer drugs directly to mitochondria. We succeeded in packaging doxorubicin (DOX) as a model cargo in MITO-Porter to produce a DOX-MITO-Porter. We evaluated cellular toxicity of OS-RC-2 cell, a type of DOX-resistant cancer cell, after delivering DOX to mitochondria using the MITO-Porter system. Cell viability was decreased by the DOX-MITO-Porter treatment, while cell viability was not decreased in the case of naked DOX and a conventional DOX liposomal formulation. We also found a relationship between cellular toxicity and mitochondrial toxicity. The use of a MITO-Porter system for mitochondrial delivery of a toxic agent represents a possible therapeutic strategy for treating drug-resistant cancers.

Original languageEnglish
Pages (from-to)2428-2437
Number of pages10
JournalJournal of Pharmaceutical Sciences
Volume106
Issue number9
DOIs
Publication statusPublished - 2017 Sep
Externally publishedYes

Keywords

  • cancer
  • drug delivery systems
  • liposomes
  • nanoparticles
  • nanotechnology

ASJC Scopus subject areas

  • Pharmaceutical Science

Fingerprint

Dive into the research topics of 'Mitochondrial Delivery of Doxorubicin Using MITO-Porter Kills Drug-Resistant Renal Cancer Cells via Mitochondrial Toxicity'. Together they form a unique fingerprint.

Cite this