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Self-assembly of peptides into spherical nanoparticles for delivery of hydrophilic moieties to the cytosol

Collins, Louise, Parker, Alan L. ORCID:, Gehman, John D., Eckley, Lorna, Perugini, Matthew A., Separovic, Frances and Fabre, John W. 2010. Self-assembly of peptides into spherical nanoparticles for delivery of hydrophilic moieties to the cytosol. ACS Nano 4 (5) , pp. 2856-2864. 10.1021/nn901414q

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We report a novel class of self-assembling peptide nanoparticles formed by mixing aqueous solutions of K16 peptide and a 20 amino acid peptide of net charge −5 (GLFEALLELLESLWELLLEA). Particle formation is salt-dependent and yields perfectly spherical nanoparticles of 120 to 800 nm diameter, depending on buffer composition and temperature, with a stoichiometry of 1:2.5 for the cationic and anionic peptides. The anionic peptide forms an α-helix in aqueous solution, has all five glutamates on one side of the helix, and exists entirely as a discrete oligomer of 9−10 peptides. A rigid oligomer with 45−50 negative charges almost certainly represents the core component of these nanoparticles, held together by electrostatic interactions with the unstructured K16 peptide. Cells internalize these particles by an endocytic process, and free particles are frequently seen in the cytosol, presumably because of the acid-dependent fusogenic properties of the anionic peptide. Among other applications, these particles have potential for the targeted delivery of single or multiple therapeutic moieties directly to the cytosol, and we report the successful delivery of a K16-linked pro-apoptosis peptide.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
Subjects: Q Science > QH Natural history > QH426 Genetics
R Medicine > RM Therapeutics. Pharmacology
Uncontrolled Keywords: peptides; nanoparticles; fusogenic peptide; drug delivery
Publisher: American Chemical Society
ISSN: 1936-0851
Last Modified: 24 Oct 2022 10:09

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