Polymer Functionalization of Isolated Mitochondria for Cellular Transplantation and Metabolic Phenotype Alteration

Suhong Wu, Aijun Zhang, Shumin Li, Somik Chatterjee, Ruogu Qi, Victor Segura-Ibarra, Mauro Ferrari, Anisha Gupte, Elvin Blanco, Dale J. Hamilton

Research output: Contribution to journalArticle

7 Scopus citations

Abstract

Aberrant mitochondrial energy transfer underlies prevalent chronic health conditions, including cancer, cardiovascular, and neurodegenerative diseases. Mitochondrial transplantation represents an innovative strategy aimed at restoring favorable metabolic phenotypes in cells with dysfunctional energy metabolism. While promising, significant barriers to in vivo translation of this approach abound, including limited cellular uptake and recognition of mitochondria as foreign. The objective is to functionalize isolated mitochondria with a biocompatible polymer to enhance cellular transplantation and eventual in vivo applications. Herein, it is demonstrated that grafting of a polymer conjugate composed of dextran with triphenylphosphonium onto isolated mitochondria protects the organelles and facilitates cellular internalization compared with uncoated mitochondria. Importantly, mitochondrial transplantation into cancer and cardiovascular cells has profound effects on respiration, mediating a shift toward improved oxidative phosphorylation, and reduced glycolysis. These findings represent the first demonstration of polymer functionalization of isolated mitochondria, highlighting a viable strategy for enabling clinical applications of mitochondrial transplantation.

Original languageEnglish (US)
Article number1700530
Pages (from-to)1700530-n/a
JournalAdvanced Science
Volume5
Issue number3
DOIs
StatePublished - Mar 1 2018

Keywords

  • Bioenergetic switches
  • Cancer
  • Cardiac failure
  • Mitochondrial transplantation
  • Surface modification/decoration

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Chemical Engineering(all)
  • Materials Science(all)
  • Biochemistry, Genetics and Molecular Biology (miscellaneous)
  • Engineering(all)
  • Physics and Astronomy(all)

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