The fluorination effect of fluoroamphiphiles in cytosolic protein delivery

Zhenjing Zhang, Wanwan Shen, Jing Ling, Yang Yan, Jingjing Hu and Yiyun Cheng ()
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Zhenjing Zhang: East China Normal University
Wanwan Shen: East China Normal University
Jing Ling: East China Normal University
Yang Yan: East China Normal University
Jingjing Hu: East China Normal University
Yiyun Cheng: East China Normal University

Nature Communications, 2018, vol. 9, issue 1, 1-8

Abstract: Abstract Direct delivery of proteins into cells avoids many drawbacks of gene delivery, and thus has emerging applications in biotherapy. However, it remains a challenging task owing to limited charges and relatively large size of proteins. Here, we report an efficient protein delivery system via the co-assembly of fluoroamphiphiles and proteins into nanoparticles. Fluorous substituents on the amphiphiles play essential roles in the formation of uniform nanoparticles, avoiding protein denaturation, efficient endocytosis, and maintaining low cytotoxicity. Structure-activity relationship studies reveal that longer fluorous chain length and higher fluorination degree contribute to more efficient protein delivery, but excess fluorophilicity on the polymer leads to the pre-assembly of fluoroamphiphiles into stable vesicles, and thus failed protein encapsulation and cytosolic delivery. This study highlights the advantage of fluoroamphiphiles over other existing strategies for intracellular protein delivery.

Date: 2018
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DOI: 10.1038/s41467-018-03779-8

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