Synthesis Of Photo, Oxidation, Reduction Triple-Stimuli-Responsive Interface-Cross-Linked Polymer Micelles As Nanocarriers For Controlled Release

Stimuli-responsive chemical bonds have already been widely applied to construct nanomaterials, however, such materials rarely have great amounts of responsive groups and stable structures. Herein, a triple-stimuli-responsive interface-cross-linked (ICL) copolymer which is synthesized via Cu(I)-catalyzed azide-alkyne cycloaddition click polymerization and atom transfer radical polymerization (ATRP), is reported. N, N '-bis(bromoacetyl) cystamine is used for intramolecular crosslinking of the linear polymer chains. The omicron-nitrobenzyl groups, peroxalate ester bonds, disulfide bonds, and triazole units are regularly and repeatedly arranged in the hydrophobic blocks, therefore enabling the polymer a large amount of responsive chemical bonds. The polymer self-assembles into spherical micelles with uniform size in deionized water. Using hydrophobic dye Nile red (NR) as a model drug to evaluate the effect of release in vitro, the multi-stimuli-sensitive release properties of the ICL micelles are investigated in detail by means of UV-vis, transmission electron microscopy, dynamic light scattering, and fluorescence spectrophotometry, and the results indicate the ICL micelles can respond to the photo, oxidation, or reduction responsiveness either independently or synergistically. Furthermore, the cross-linked structure enhances the stability of the micelles and rarely impacts the total amount of drug release. The research may have applications in the field of drug delivery systems for cancer therapy.