Synthesis of temperature, pH, light and dual-redox quintuple-stimuli-responsive shell-crosslinked polymeric...

Herein, we prepared a novel quintuple-stimuli-responsive shell-crosslinked (SCL) nanocontainer in respond to temperature, pH, light, and oxidation or reduction species. The well-defined amphiphilic diblock copolymer poly(2-methacryloyloxyethyl ferrocenecarboxylate)-(5-propargylether-2-nitrobenzyl bromoisobutyrate)-poly(dimethylaminoethyl methacrylate) (PMAEFc-ONB-PDMAEMA) was synthesized via atom transfer radical polymerization (ATRP) and click chemistry. The diblock copolymer self-assembled into spherical micelles with a uniform size in aqueous media as non-crosslinked (NCL) micelles, and then the micelles were crosslinked by N,N'-bis(bromoacetyl) cystamine (BBAC) through quaternization reaction between the nitrogen of DMAEMA and the bromine of BBAC to receive the SCL micelles which shrunk at higher temperature, swelled at acidic pH or a low concentration of hydrogen peroxide (H₂O₂), decrosslinked by a small amount of DL-dithiothreitol (DTT), and were disrupted with DTT and UV light. The multi-stimuli-sensitive properties of the SCL micelles were characterized in detail by dynamic light scattering (DLS), transmission electron microscopy (TEM), fluorescence spectra, and UV-Vis spectra. Owing to the protective effect of the crosslinked network, light response behaviors of the NCL and SCL micelles were different. In contrast to the single stimulus, the combined stimuli could trigger and regulate the release of hydrophobic drug model more effectively and precisely from the SCL micelles. The obtained multi-stimuli-responsive nanocontainers may lead to a new generation of controlled release in the fields of nanotechnology and biotechnology.