Display omitted •The SPNH/DOX nanoplatform presented controlled drug delivery with a chemo selective approach for chemotherapy.•The copolymer of (NIPAm)-(NHMA) served as temperature-sensitive polymeric carrier.•In-depth study of drug release mechanism using different mathematical equation models.•The synergistic anticancer efficacy of SPNH/DOX was boosted by the combined approach. 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.