Simultaneous photo-magnetic dual hyperthermia combined with radiotherapy enhanced by snowman‑shaped Janus nanoparticles in CT26 colon cancer model

• Snowman-shaped Janus nanoparticles enable targeted magnetic tumor delivery. • Combined photo-magnetic hyperthermia and radiotherapy significantly reduce colon tumor growth. • Nanoparticles enhance MRI imaging and show excellent biocompatibility. • Dual therapy elevates VEGF and Hsp70, improving treatment efficacy and survival. Colon cancer is the third most common malignant tumor worldwide with high mortality. This study developed snowman-shaped Janus nanoparticles (JNPs) (Fe 3 O 4 -Au@poly(NIPAAm-co-AAM-co-AA)) for targeted cancer therapy by combining photomagnetic hyperthermia and radiotherapy. JNPs were synthesized and characterized using TEM and SEM, confirming their size (85.3 ± 4.1 nm). Cytotoxicity on CT26 cells was evaluated via MTT assay. Cellular uptake, in vivo biodistribution, and potential hepatic damage were evaluated through ICP-OES and liver enzyme measurements. MRI was utilized to study tumor targeting, while temperature changes laser exposure, and alternating magnetic field (AMF) conditions were monitored using an IR camera. Western blotting assessed Hsp70, and VEGF protein expression. In addition, histological examination, tumor volume, and survival time in CT26 colon tumor-bearing mice were monitored to assess the antitumor efficacy of the JNPs. The JNPs demonstrated good hemocompatibility and effective magnetic tumor targeting in MRI studies. In vivo experiments showed significant tumor volume reduction and increased Hsp70 and VEGF expression in mice treated with the combination of JNPs, radiotherapy, and concurrent AMF and NIR hyperthermia (p < 0.0001). The JNPs are promising as multifunctional platforms for cancer therapy, demonstrating excellent biocompatibility, magnetic targeting, and enhanced hyperthermia and radiotherapy, which may improve treatment outcomes in targeted multimodal cancer therapies.