Development and structural analysis of dual-thermo-responsive self-assembled zwitterionic micelles

Abstract

Multi-stimuli-responsive materials may dominate next-generation drug delivery systems. Herein, dual-thermo-responsive micelles were prepared by introducing cholesterol chloroformate to facilitate the spontaneous self-assembly of graft polymers prepared by combining two charged polymers, poly-sulfobetaine and carboxylated ε-poly-L-lysine. This polymerization was controlled by reversible addition fragmentation chain transfer polymerization. Turbidimetry measurements and temperature-dependent ¹H NMR spectroscopy were used to investigate the phase transition behaviors; transmission electron microscopy and atomic force microscopy were used to determine the morphology of the micelles. The dependence of self-assembled structures on temperature was investigated through ultra-small-angle X-ray scattering (USAXS). The micelles formed spherical shapes in water which was confirmed by TEM and AFM. Interestingly, different, temperature-dependent micelle size change behaviors were observed through dynamic light scattering, Ultraviolet-visible (UV-Vis) spectroscopy, and USAXS; this might be due to the concentration-dependent hierarchical phase transition. This study provides crucial information on the mesoscopic structure of the micelles, and will enable greater control over their transition temperatures for numerous biomaterial applications.