Selective Enzymatic Degradation of Self-Assembled Particles from Amphiphilic Block Copolymers Obtained by the Combination of N-Carboxyanhydride and Nitroxide-Mediated Polymerization
journal contributionposted on 10.10.2011, 00:00 by Gijs J. M. Habraken, Marloes Peeters, Paul D. Thornton, Cor E. Koning, Andreas Heise
Combining controlled radical polymerizations and a controlled polypeptide synthetic technique, such as N-carboxyanhydride (NCA) ring-opening polymerization, enables the generation of well-defined block copolymers to be easily accessible. Here we combine NCA polymerization with the nitroxide-mediated radical polymerization of poly(n-butyl acrylate) (PBA) and polystyrene (PS), using a TIPNO and SG1-based bifunctional initiator to create a hybrid block copolymer. The polypeptide block consists of (block) copolymers of poly(l-glutamic acid) embedded with various quantities of l-alanine. The formed superstructures (vesicles and micelles) of the block copolymers possessed varying degrees of enzyme responsiveness when exposed to elastase and thermolysin, resulting in controlled enzymatic degradation dictated by the polypeptide composition. The PBA containing block copolymers possessing 50% l-alanine in the polypeptide block showed a high degradation response compared to polymers containing lower l-alanine quantities. The particles stabilized by copolypeptides with l-alanine near the hydrophobic block showed full degradation within 4 days. Particles containing polystyrene blocks revealed no appreciable degradation under the same conditions, highlighting the specificity of the system and the importance of synthetic polymer selection. However, when the degradation temperature was increased to 70 °C, degradation could be achieved due to the higher block copolymer exchange between the particle and the solution. A number of novel biohybrid structures are disclosed that show promise as enzyme-responsive materials with potential use as payload release vehicles, following their controlled degradation by specific, target, enzymes.