Self-Assembly of Peptides into Spherical Nanoparticles for Delivery of Hydrophilic Moieties to the Cytosol

TY - JOUR

T1 - Self-Assembly of Peptides into Spherical Nanoparticles for Delivery of Hydrophilic Moieties to the Cytosol

AU - Collins, Louise

AU - Parker, Alan L.

AU - Gehman, John D.

AU - Eckley, Lorna

AU - Perugini, Matthew A.

AU - Separovic, Frances

AU - Fabre, John W.

PY - 2010/5/25

Y1 - 2010/5/25

N2 - We report a novel class of self-assembling peptide nanoparticles formed by mixing aqueous solutions of K-16 peptide and a 20 amino acid peptide of net charge -5 (GLFEALLELLESLWELLLEA). Particle formation is salt-dependent and yields perfectly spherical nanoparticles of similar to 120 to similar to 800 nm diameter, depending on buffer composition and temperature, with a stoichiometry of similar to 1:2.5 for the cationic and anionic peptides. The anionic peptide forms an cc-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 almost certainly represents the core component of these nanoparticles, held together by electrostatic with the unstructured K-16 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 K-16-linked pro-apoptosis peptide.

AB - We report a novel class of self-assembling peptide nanoparticles formed by mixing aqueous solutions of K-16 peptide and a 20 amino acid peptide of net charge -5 (GLFEALLELLESLWELLLEA). Particle formation is salt-dependent and yields perfectly spherical nanoparticles of similar to 120 to similar to 800 nm diameter, depending on buffer composition and temperature, with a stoichiometry of similar to 1:2.5 for the cationic and anionic peptides. The anionic peptide forms an cc-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 almost certainly represents the core component of these nanoparticles, held together by electrostatic with the unstructured K-16 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 K-16-linked pro-apoptosis peptide.

U2 - 10.1021/nn901414q

DO - 10.1021/nn901414q

M3 - Article

SN - 1936-086X

VL - 4

SP - 2856

EP - 2864

JO - ACS Nano

JF - ACS Nano

IS - 5

ER -