Thermo-responsive-polymeric-gates of poly(N-isopropylacrylamide)/N-(hydroxymethyl)acrylamide coated magnetic nanoparticles as a synergistic approach to cancer therapy: Drug release and kinetics models of chemothermal magnetic nanoparticles

The study presents a controlled nanoscale drug delivery system mediated by polymeric magnetic nanoparticles. Under an alternating magnetic field (AMF), the magnetic nanoparticles act as internal heating sources that increase the surrounding temperature, provoking polymer transitions and thereby releasing the entrapped drug. We explain the drug-release mechanism using different mathematical models including Higuchi, Korsmeyer–Peppas, Hixson–Crowell, and Kopcha. Our results indicate that doxorubicin (DOX) release follows the Hixson–Crowell model with R² = 0.99, revealing that the changes in the surface areas of the particles are the main driving force for drug release from poly(N-isopropylacrylamide)/N (hydroxymethyl) acrylamide coated SPIONs (SPNH/DOX) at 43 °C. However, at 37 °C, the drug release occurs by the diffusion mechanism. Moreover, in vitro cell culture assays including CCK-8, FACS, confocal and BIO-TEM images have confirmed cytotoxicity and cellular uptake of SPNH/DOX in CT26 cancer cells. Through a synergetic effect between chemotherapy triggered by AMF application and intracellular hyperthermia, significant tumoricidal effects were achieved in the initial 24 h after treatment.