Dual temperature- and magnetic-responsive PNIPAAm-based nanogels for tunable and drug release.
Dual-responsive magnetic nanogels based on poly(N-isopropylacrylamide) (PNIPAAm) and carboxymethyl dextran-modified magnetic nanoparticles (CM-Dex-MNPs) were synthesized and systematically investigated as thermo-magnetic drug delivery carriers. Unlike conventional approaches that regulate the lower critical solution temperature (LCST) through copolymerization with additional hydrophilic monomers, CM-Dex-MNPs were directly employed as multifunctional building blocks to simultaneously provide magnetic responsiveness and modulate the hydrophilicity of the PNIPAAm network. The successful formation of the nanogel system was confirmed by FTIR, 1H NMR, XPS, TEM, DLS, TGA, and SQUID analyses. Increasing CM-Dex-MNP content resulted in larger particle size, enhanced magnetic properties, and elevated LCST, demonstrating that thermo-responsive behavior could be effectively tailored through composition control. Hesperetin-loaded nanogels exhibited temperature-dependent drug release, while alternating magnetic field (AMF) stimulation further accelerated drug release. Release kinetics were analyzed using the Box-Lucas model, and the heating capability under AMF was quantified by the specific absorption rate (SAR), providing mechanistic insight into AMF-enhanced drug release. Furthermore, increasing magnetic nanoparticle content improved drug loading and encapsulation efficiencies and enhanced thermo-magnetic responsiveness. These findings demonstrate that regulating CM-Dex-MNP content provides a simple and effective strategy for simultaneously tuning LCST, magnetic properties, and drug release behavior, offering useful design principles for dual-responsive magnetic nanogel-based drug delivery systems.