<br>分离线粒体的聚合物功能化用于细胞移植和代谢表型改变,Advanced Science

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分离线粒体的聚合物功能化用于细胞移植和代谢表型改变
Advanced Science ( IF 14.3 ) Pub Date : 2018-01-03 , DOI: 10.1002/advs.201700530
Suhong Wu ₁ , Aijun Zhang ₂ , Shumin Li ₂ , Somik Chatterjee ₂ , Ruogu Qi ₁ , Victor Segura-Ibarra ₁ , Mauro Ferrari _{1,

3} , Anisha Gupte _{2,

4} , Elvin Blanco ₁ , Dale J Hamilton _{2,

3,

5}

Affiliation

异常的线粒体能量转移是常见慢性健康状况的基础，包括癌症、心血管和神经退行性疾病。线粒体移植代表了一种创新策略，旨在恢复能量代谢功能失调的细胞中有利的代谢表型。尽管前景广阔，但这种方法在体内翻译的重大障碍比比皆是，包括有限的细胞摄取和将线粒体识别为外来物。目的是用生物相容性聚合物对分离的线粒体进行功能化，以增强细胞移植和最终的体内应用。本文证明，与未包被的线粒体相比，将由葡聚糖与三苯基鏻组成的聚合物缀合物接枝到分离的线粒体上可以保护细胞器并促进细胞内化。重要的是，线粒体移植到癌症和心血管细胞中对呼吸具有深远的影响，介导向改善氧化磷酸化和减少糖酵解的转变。这些发现首次证明了分离线粒体的聚合物功能化，强调了实现线粒体移植临床应用的可行策略。

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

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.

更新日期：2018-01-03

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