Multi-Stimuli-Responsive Performance And Morphological Changes Of Radical-Functionalized Self-Assembled Micellar Nanoaggregates And Their Multi-Triggered Drug Release

Stimuli-responsive self-assembled nanostructures are of great interest as smart materials in different industries, but there are limitations to obtain such materials in radical-functionalized amphiphilic random copolymers owing to structural illness. Herein, a series of novel radical-functionalized poly(N-isopropyl methacrylamide-coacrylic acid)s (RF-p(NIPMAM-co-AA)s) amphiphilic random copolymers were synthesized and their selfassembled nanostructures were studied by electron spin resonance (ESR) with other analytical techniques. ESR spectroscopy and TEM revealed the formation of smart supramolecular nanoaggregates (SNAs), their multistimuli-responsiveness and morphological transitions in different external parameters (e.g. pH, temperature, reductant, polarity and viscosity), hence, ESR spectroscopy provides the dynamics of inter and/or intramolecular interactions of polymer chains dependent on nanomaterial's environments. At a more acidic medium, the colloidal nanoparticles were shown to disassemble due to the disproportionation of nitroxide radicals. The particles' morphology was observed to be a lower critical solution temperature (LCST) type, where multimicelle aggregates were formed upon increasing the temperature. The kinetically controlled redox-triggered disassembly was noticed upon the addition of different molar equivalents of vitamin C (VC) as a reducing agent. Interestingly, the morphological transitions were observed on changing the polarity of the medium, whereas THF and 1-octanol were used as nonpolar solvents. These observations are helpful to yield insight into the structure-property relationship of colloidal supramolecular nanosystems and could be used to design similar spontaneous and controlled self-assembled nanostructures by regulating the microenvironments. The biocompatibility of the assemblies was investigated by hemolysis assay. As a proof-of-concept demonstration, we utilized the nanoaggregates as an anticancer drug carrier in multi-triggered release systems.