Stimuli-sensitivity and dynamics in the self-assembly structure of TEMPO-containing nonamphiphilic nanoparticles and their triggering hydrophobic drug release

Understanding the dynamics of stimuli-sensitive self-assembled nanomaterials is crucial for their potential applications, however, it is relatively difficult to quantitatively probe the dynamics using conventional analytical techniques because of the low sensitivity and selectivity of these techniques. In this research, TEMPO-containing nonamphiphilic copolymers are synthesized and highly sensitive, selective and non-destructive electron spin resonance (ESR) spectroscopy is applied to study their dynamics in stimuli-sensitive self-assembled nano-structures in different microenvironments. ESR spectroscopy reveals the structural changes of the smart supra-molecular nanoparticles (SNPs) in their controlled assemblies by observing the molecular-level interactions. In order to obtain the dynamical evidence, several spectroscopic parameters such as rotational correlation time, hyperfine splitting constant, intensity increase/decrease and anisotropy parameters are determined from the ESR spectra. The stimuli-sensitivity and dynamics strongly depend on the SNPs' microenvironment correlated to several chemical and physiological parameters such as radical concentration, pH, redox agent, temperature, polarity and viscosity. The results provide quantitative insights into the interface of the supramolecular assemblies. The nanoparticles showed good biocompatibility confirmed by the hemolysis test and the MTT assay. Furthermore, proof-of-concept experiments were carried out to demonstrate the SNPs' stimuli-sensitive performance as a hydrophobic anticancer drug nanocarrier. This effort can be used to design other colloidal nanoplatforms for the potential application in cancer treatment.