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Polyarginine segments in block copolypeptides drive both vesicular assembly and intracellular delivery

Abstract

Polymeric vesicles are a relatively new class of nanoscale self-assembled materials that show great promise as robust encapsulants. Compared with liposomes, use of polymeric building blocks for membrane formation allows increased stability, stimuli responsiveness and chemical diversity, which may prove advantageous for drug-delivery applications 1. A major drawback of most polymeric vesicles is the lack of biofunctionality, which restricts their ability to interact with cells and tissues. We have prepared vesicles composed of polyarginine and polyleucine segments that are stable in media, can entrap water soluble species, and can be processed to different sizes and prepared in large quantities. The remarkable feature of these materials is that the polyarginine segments both direct structure for vesicle formation and provide functionality for efficient intracellular delivery of the vesicles. This unique synergy between nanoscale self-assembly and inherent peptide functionality provides a new approach for design of multifunctional materials for drug delivery.

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Figure 1: Formation and properties of R60L20 vesicles.
Figure 2: Transport of polypeptide vesicles across bulk membranes.
Figure 3: Transport of polypeptide vesicles into cells in vitro.

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Acknowledgements

This work was supported by a grant from the National Science Foundation (CHE-0415275) to T.J.D. and by a Sidney Kimmel Scholar Award to D.T.K.

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E.P.H. and V.Z.S.: experimental work and data analysis; T.J.D. and D.T.K.: project planning, data analysis and manuscript writing.

Corresponding author

Correspondence to Timothy J. Deming.

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The authors declare no competing financial interests.

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Supplementary Information

Supplementary information and figures S1-S3 (PDF 185 kb)

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Holowka, E., Sun, V., Kamei, D. et al. Polyarginine segments in block copolypeptides drive both vesicular assembly and intracellular delivery. Nature Mater 6, 52–57 (2007). https://doi.org/10.1038/nmat1794

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