Polymer Functionalization of Isolated Mitochondria for Cellular Transplantation and Metabolic Phenotype Alteration. Issue 3 (3rd January 2018)

• Record Type: Journal Article
• Authors: Wu, Suhong; Zhang, Aijun; Li, Shumin; Chatterjee, Somik; Qi, Ruogu; Segura‐Ibarra, Victor; Ferrari, Mauro; Gupte, Anisha; Blanco, Elvin; Hamilton, Dale J.
• Is Part Of: Advanced science. Volume 5:Issue 3(2018)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2018-01-03
• Subjects: bioenergetic switches -- cancer -- cardiac failure -- mitochondrial transplantation -- surface modification/decoration; Science -- Periodicals; 505
• DOI: 10.1002/advs.201700530
• Languages: English
• ISSNs: 2198-3844

Abstract

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. Abstract : Metabolic impairment is a hallmark of various diseases. Herein, it is aimed to polymerically functionalize the surface of isolated mitochondria to facilitate transplantation into metabolically compromised cells. These results demonstrate that coating mitochondria enhanced their preservation ex vivo, increased their internalization within cancer and cardiac cells, and induced a superior shift in the metabolic phenotype of these cells compared with uncoated mitochondria.