The Production of Polysarcosine‐Containing Nanoparticles by Ring‐Opening Polymerization‐Induced Self‐Assembly

Abstract

N‐carboxyanhydride ring‐opening polymerisation‐induced self‐assembly (NCA ROPISA) offers a convenient route for generating poly(amino acid)‐based nanoparticles in a single step, crucially avoiding the need for post‐polymerisation self‐assembly. Most examples of NCA ROPISA make use of a poly(ethylene glycol) hydrophilic stabilising block, however this non‐biodegradable, oil‐derived, polymer and may cause an immunological response in some individuals. Alternative water‐soluble polymers are therefore highly sought. We report the synthesis of wholly poly(amino acid)‐based nanoparticles, through the chain‐extension of a polysarcosine macroinitiator with L‐Phenylalanine‐NCA (L‐Phe‐NCA) and Alanine‐NCA (Ala‐NCA), via aqueous NCA ROPISA. The resulting polymeric structures comprise of predominantly anisotropic, rod‐like nanoparticles, with morphologies primarily influenced by the secondary structure of the hydrophobic poly(amino acid) that enables their formation.This article is protected by copyright. All rights reserved

Poly(l-proline)-Stabilized Polypeptide Nanostructures via Ring-Opening Polymerization-Induced Self-Assembly (ROPISA)

“…The hydrophobic PBLG or PZLL blocks are assumed to form the core while interacting through their secondary structures, for example, helix–helix or β-sheet interactions (Figure B–D). Specifically the formation of anisotropic and elongated nanoparticles from amphiphilic block copolymers containing PBLG has been reported in previous studies in agreement with the structures observed here. − ,, It is usually ascribed to antiparallel helix–helix alignment.…”

“…More desirable are nanostructures fully derived from amino acids for reasons of biocompatibility and degradability and as simplistic biomimetic models of natural proteins. Very recently Thornton et al and Bonduelle et al independently reported aqueous ROPISA using poly(sarcosine) and polyLPro as hydrophilic blocks. , In both cases, nanostructures were obtained in a two-step process initiating NCA chain extension from preformed macroinitiators using Schlenk line and glovebox procedures. The challenge for a fully NCA ROPISA process lies in the fact that all proteogenic amino acid NCAs are hydrophobic, if not intrinsically, then through side chain protection, while a successful PISA process relies on in situ generation of amphiphilicity.…”