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Self-assembling asymmetric peptide-dendrimer micelles – a platform for effective and versatile in vitro nucleic acid delivery

Kokil, G.R., Veedu, R.N., Le, B.T., Ramm, G.A. and Parekh, H.S. (2018) Self-assembling asymmetric peptide-dendrimer micelles – a platform for effective and versatile in vitro nucleic acid delivery. Scientific Reports, 8 (1).

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Abstract

Despite advancements in the development of high generation cationic-dendrimer systems for delivery of nucleic acid-based therapeutics, commercially available chemical agents suffer from major drawbacks such as cytotoxicity while being laborious and costly to synthesize. To overcome the aforementioned limitations, low-generation cationic peptide asymmetric dendrimers with side arm lipid (cholic and decanoic acid) conjugation were designed, synthesized and systematically screened for their ability to self-assemble into micelles using dynamic light scattering. Cytotoxicity profiling revealed that our entire asymmetric peptide dendrimer library when trialled alone, or as asymmetric dendrimer micelle-nucleic acid complexes, were non-cytotoxic across a broad concentration range. Further, the delivery efficiency of asymmetric peptide dendrimers in H-4-II-E (rat hepatoma), H2K (mdx mouse myoblast), and DAOY (human medulloblastoma) cells demonstrated that cholic acid-conjugated asymmetric dendrimers possess far superior delivery efficiency when compared to the commercial standards, Lipofectamine 2000 or Lipofectin®.

Item Type: Journal Article
Murdoch Affiliation(s): Centre for Comparative Genomics
Publisher: Springer Nature
Copyright: © 2018 The Author(s)
URI: http://researchrepository.murdoch.edu.au/id/eprint/40616
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