Multi-stimuli-responsive performance and morphological changes of radical-functionalized self-assembled micellar nanoaggregates and their multi-triggered drug release

Abstract

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- co -acrylic acid)s (RF-p(NIPMAM-co-AA)s) amphiphilic random copolymers were synthesized and their self-assembled 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 multi-stimuli-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 intra-molecular 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 multi-micelle 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. • Multi-stimuli-responsive performance of stable radical-functionalized nanoparticles has been reported. • Dynamical and structural information has been investigated by electron spin resonance spectroscopy. • Proof-of-concept demonstration was proved their multi-triggered application in anticancer drug delivery. • This design promotes a robust and simple synthesis of spontaneous and controlled stimuli-responsive nanosystems.