In Situ Formation of Nanoparticles from Graft Copolypeptides Under Dispersion Polymerization Conditions

Abstract

A simple method is presented for preparing polypeptide nanoparticles using hydrophilic biosynthetic ε-poly(lysine) (εPL) as a reactive surfactant under dispersion polymerization conditions. In situ graft polymerization of benzyl-L-glutamic acid N-carboxyanhydride (BLG-NCA) triggers the self-assembly of amphiphilic copolymers into nanoparticles, which are colloidally stabilized by the remaining εPL amino groups at the particle surface. The average nanoparticle diameter can be controlled in the range of 40–120 nm by varying the initiator-to-NCA ratio, as demonstrated by the correlation between graft copolymer molecular weight (measured by size exclusion chromatography) and the z-average diameter (measured by dynamic light scattering). Secondary structure analysis indicates that the α-helical conformation of poly(benzyl-L-glutamate) (PBLG) grafts plays a role in both accelerating NCA polymerization and stabilizing the nanostructures. This approach is readily scalable to high concentrations and offers a straightforward route to peptidomimetic nanoparticles, entirely composed of amino acids, with promising potential for nanomedicine applications.