Synthesis of redox-responsive core–shell nanoparticles: insights into core-crosslinking efficiency

Abstract

Core-crosslinked micelles have become an important class of materials for biomedical applications. However, there has been little work attempting to quantify the efficiency of the core crosslinking reaction, instead residual polymers are usually removed by dialysis. In this work we have prepared core crosslinked micelles based on poly(2-ethyl-2-oxazoline)-block-poly(n-butyl acrylate-co-D,L-homocysteine thiolactone acrylamide). Core crosslinking was examined by the addition of six different di- and triamines and nucleophilic ring-opening of the thiolactone ring. By using size exclusion chromatography (SEC) we were able to quantify the amount of crosslinked micelle and free block copolymer and were able to optimize the crosslinking conditions in terms of temperature, reaction time and crosslinker equivalents to obtain up to 80% core-crosslinked micelles. Subsequently, micelles that were crosslinked with cystamine were degraded in the presence of dithiothreitol (DTT) and resulted in degradation times of 1.5 h to 5 h and depended strongly on the composition of the hydrophobic core as shown by dynamic light scattering (DLS) and size exclusion chromatography (SEC). Cytotoxicity assays of the core-crosslinked micelles and block copolymer precursors were performed with COS7 cells and revealed high cell viabilities up to 0.1 mg mL−1.