Facile Construction of Polyoxometalate-Polymer Hybrid Nanoparticles with pH/Redox Dual-Responsiveness.

Abstract

Responsive nanomaterials have emerged as promising candidates for advanced drug delivery systems (DDSs), offering the potential to precisely target disease sites and enhance treatment efficacy. To fulfil their potential, such materials need to be engineered to respond to specific variations in biological conditions. In this work, we present a series of pH/redox dual-responsive hybrid nanoparticles featuring an amphiphilic shell polymer and a pH-responsive core polymer. These nanoparticles incorporate a polyoxometalate (POM), specifically the cobalt(III)-substituted borotungstate ([BIIIW11O39CoIII]6-), loaded through coordination chemistry between the encapsulated CoIII ions of the POM and pyridyl functional groups on the core polymer. The resulting hybrid nanoparticles show potential for controlled release with excellent stability at physiological pH, and efficient particle disassembly in response to the combination of pH and redox stimuli. Disassembly is proposed to occur following a two step mechanism. Structural rearrangement of the nanoparticle occurs on acidification followed by destabilization of the coordination bond between the polyanion and the pyridyl functionality in the core polymer following reduction. This showcased the viability of the material design whereby the POM serves as a redox active structural cross-linker. These hybrid dual-responsive nanoparticles, featured superior colloidal stability under extracellular conditions and controllable disintegration in response to the dual stimuli of acidic pH and redox conditions, provide a novel platform for the controlled intracellular release of therapeutics.