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

Research output: Contribution to journalArticle

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

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

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Polymer Functionalization of Isolated Mitochondria for Cellular Transplantation and Metabolic Phenotype Alteration. / Wu, Suhong; Zhang, Aijun; Li, Shumin; Chatterjee, Somik; Qi, Ruogu; Segura-Ibarra, Victor; Ferrari, Mauro; Gupte, Anisha; Blanco, Elvin; Hamilton, Dale J.

In: Advanced Science, Vol. 5, No. 3, 1700530, 01.03.2018, p. 1700530-n/a.

Research output: Contribution to journalArticle

Harvard

Wu, S, Zhang, A, Li, S, Chatterjee, S, Qi, R, Segura-Ibarra, V, Ferrari, M, Gupte, A, Blanco, E & Hamilton, DJ 2018, 'Polymer Functionalization of Isolated Mitochondria for Cellular Transplantation and Metabolic Phenotype Alteration' Advanced Science, vol. 5, no. 3, 1700530, pp. 1700530-n/a. https://doi.org/10.1002/advs.201700530

APA

Wu, S., Zhang, A., Li, S., Chatterjee, S., Qi, R., Segura-Ibarra, V., ... Hamilton, D. J. (2018). Polymer Functionalization of Isolated Mitochondria for Cellular Transplantation and Metabolic Phenotype Alteration. Advanced Science, 5(3), 1700530-n/a. [1700530]. https://doi.org/10.1002/advs.201700530

Vancouver

Wu S, Zhang A, Li S, Chatterjee S, Qi R, Segura-Ibarra V et al. Polymer Functionalization of Isolated Mitochondria for Cellular Transplantation and Metabolic Phenotype Alteration. Advanced Science. 2018 Mar 1;5(3):1700530-n/a. 1700530. https://doi.org/10.1002/advs.201700530

Author

Wu, Suhong ; Zhang, Aijun ; Li, Shumin ; Chatterjee, Somik ; Qi, Ruogu ; Segura-Ibarra, Victor ; Ferrari, Mauro ; Gupte, Anisha ; Blanco, Elvin ; Hamilton, Dale J. / Polymer Functionalization of Isolated Mitochondria for Cellular Transplantation and Metabolic Phenotype Alteration. In: Advanced Science. 2018 ; Vol. 5, No. 3. pp. 1700530-n/a.

BibTeX

@article{785ce586a5ef454699acd9131065a452,
title = "Polymer Functionalization of Isolated Mitochondria for Cellular Transplantation and Metabolic Phenotype Alteration",
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.",
keywords = "Bioenergetic switches, Cancer, Cardiac failure, Mitochondrial transplantation, Surface modification/decoration",
author = "Suhong Wu and Aijun Zhang and Shumin Li and Somik Chatterjee and Ruogu Qi and Victor Segura-Ibarra and Mauro Ferrari and Anisha Gupte and Elvin Blanco and Hamilton, {Dale J.}",
note = "1700530",
year = "2018",
month = "3",
day = "1",
doi = "10.1002/advs.201700530",
language = "English (US)",
volume = "5",
pages = "1700530--n/a",
journal = "Advanced Science",
issn = "2198-3844",
publisher = "Wiley",
number = "3",

}

RIS

TY - JOUR

T1 - Polymer Functionalization of Isolated Mitochondria for Cellular Transplantation and Metabolic Phenotype Alteration

AU - Wu, Suhong

AU - Zhang, Aijun

AU - Li, Shumin

AU - Chatterjee, Somik

AU - Qi, Ruogu

AU - Segura-Ibarra, Victor

AU - Ferrari, Mauro

AU - Gupte, Anisha

AU - Blanco, Elvin

AU - Hamilton, Dale J.

N1 - 1700530

PY - 2018/3/1

Y1 - 2018/3/1

N2 - 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.

AB - 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.

KW - Bioenergetic switches

KW - Cancer

KW - Cardiac failure

KW - Mitochondrial transplantation

KW - Surface modification/decoration

UR - http://www.scopus.com/inward/record.url?scp=85039988513&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85039988513&partnerID=8YFLogxK

U2 - 10.1002/advs.201700530

DO - 10.1002/advs.201700530

M3 - Article

VL - 5

SP - 1700530-n/a

JO - Advanced Science

T2 - Advanced Science

JF - Advanced Science

SN - 2198-3844

IS - 3

M1 - 1700530

ER -

ID: 38830922