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Cationic amphiphilic polyproline helix P11LRR targets intracellular mitochondria

Authors
Journal
Journal of Controlled Release
0168-3659
Publisher
Elsevier
Publication Date
Volume
142
Issue
2
Identifiers
DOI: 10.1016/j.jconrel.2009.10.012
Keywords
  • Cell Penetrating Peptide
  • Mitochondria
  • Ros
  • Endocytosis
  • Membrane Translocation
Disciplines
  • Chemistry

Abstract

Abstract We demonstrate that P11LRR, a recently developed amphiphilic polyproline, cell penetrating agent, is able to locate inside the mitochondria of various cell lines when administrated at high concentrations. Mitochondrial targeting was verified by confocal fluorescence co-localization of P11LRR-fluorescein with Mitotracker Red. Elimination of mitochondrial membrane potential dramatically inhibits the localization of P11LRR to mitochondria. Concentration-dependency experiments suggest that cellular internalization of P11LRR occurs via two different pathways: endocytosis and direct transport. Results indicate that the latter pathway predominates at high concentrations of P11LRR, resulting in localization of the agent to the mitochondria. The membrane translocation pathway was further confirmed by two endocytosis inhibitors, cytochalasin D and phenylarsine oxide, and by modulation of plasma membrane potential. The potential of using P11LRR as a mitochondrial drug delivery vector was demonstrated through the delivery of a covalently linked small antioxidant, dimethyltyrosine (Dmt), which allowed for the reduction of chemically induced reactive oxygen species within the mitochondria.

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