New therapeutic approaches are needed for the management of the highly chemo- and radioresistant chondrosarcoma (CHS). In this work, we used polyethylene glycol-encapsulated iron oxide nanoparticles for the intracellular delivery of the chemotherapeutic doxorubicin (IONPDOX) to augment the cytotoxic effects of carbon ions in comparison to photon radiation therapy. The in vitro biological effects were investigated in SW1353 chondrosarcoma cells focusing on the following parameters: cell survival using clonogenic test, detection of micronuclei (MN) by cytokinesis blocked micronucleus assay and morphology together with spectral fingerprints of nuclei using enhanced dark-field microscopy (EDFM) assembled with a hyperspectral imaging (HI) module. The combination of IONPDOX with ion carbon or photon irradiation increased the lethal effects of irradiation alone in correlation with the induction of MN. Alterations in the hyperspectral images and spectral profiles of nuclei reflected the CHS cell biological modifications following the treatments, highlighting possible new spectroscopic markers of cancer therapy effects. These outcomes showed that the proposed combined treatment is promising in improving CHS radiotherapy.
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