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Human 2D CHS SW1353 cells were treated with protons (linear energy transfer (LET): 1.6 and 12.6 keV\/\u00b5m) with and without IONPDOX. Cell survival was assayed using a clonogenic test, and genotoxicity was tested through the formation of micronuclei (MN) and \u03b3H2AX foci, respectively. Morphology together with spectral fingerprints of nuclei were measured using enhanced dark-field microscopy (EDFM) assembled with a hyperspectral imaging (HI) module and an axial scanning fluorescence module, as well as scanning electron microscopy (SEM) coupled with energy-dispersive X-Ray spectroscopy (EDX). Cell survival was also determined in 3D SW3153 spheroids following treatment with low-LET protons with\/without the IONPDOX compound. IONPDOX increased radiosensitivity following proton irradiation at both LETs in correlation with DNA damage expressed as MN or \u03b3H2AX. The IONPDOX\u2013low-LET proton combination caused a more lethal effect compared to IONPDOX\u2013high-LET protons. CHS cell biological alterations were reflected by the modifications in the hyperspectral images and spectral profiles, emphasizing new possible spectroscopic markers of cancer therapy effects. Our findings show that the proposed treatment combination has the potential to improve the management of CHS.<\/jats:p>","DOI":"10.3390\/ijms252111481","type":"journal-article","created":{"date-parts":[[2024,10,25]],"date-time":"2024-10-25T10:50:08Z","timestamp":1729853408000},"page":"11481","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Enhancing Proton Radiosensitivity of Chondrosarcoma Using Nanoparticle-Based Drug Delivery Approaches: A Comparative Study of High- and Low-Energy Protons"],"prefix":"10.3390","volume":"25","author":[{"given":"Mihaela","family":"Tudor","sequence":"first","affiliation":[{"name":"Department of Life and Environmental Physics, Horia Hulubei National Institute of Physics and Nuclear Engineering, Reactorului 30, P.O. Box MG-6, 077125 Magurele, Romania"},{"name":"Faculty of Biology, University of Bucharest, Splaiul Independentei 91-95, 050095 Bucharest, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Roxana Cristina","family":"Popescu","sequence":"additional","affiliation":[{"name":"Department of Life and Environmental Physics, Horia Hulubei National Institute of Physics and Nuclear Engineering, Reactorului 30, P.O. Box MG-6, 077125 Magurele, Romania"},{"name":"Department of Bioengineering and Biotechnology, Faculty of Medical Engineering, National University for Science and Technology Politehnica of Bucharest, Gheorghe Polizu Street, 1-7, 011061 Bucharest, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ionela N.","family":"Irimescu","sequence":"additional","affiliation":[{"name":"Applied Sciences Doctoral School, National University for Science and Technology Politehnica of Bucharest, 060042 Bucharest, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ann","family":"Rzyanina","sequence":"additional","affiliation":[{"name":"Laboratory of Nuclear Problems, Joint Institute for Nuclear Research, 6 Joliot-Curie Street, 141980 Dubna, Moscow Region, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7769-8289","authenticated-orcid":false,"given":"Nicolae","family":"Tarba","sequence":"additional","affiliation":[{"name":"Doctoral School of Computer Sciences, National University for Science and Technology Politehnica of Bucharest, 060042 Bucharest, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anca","family":"Dinischiotu","sequence":"additional","affiliation":[{"name":"Faculty of Biology, University of Bucharest, Splaiul Independentei 91-95, 050095 Bucharest, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-9006-217X","authenticated-orcid":false,"given":"Liviu","family":"Craciun","sequence":"additional","affiliation":[{"name":"Radiopharmaceutical Research Centre, Horia Hulubei National Institute of Physics and Nuclear Engineering, 077125 Magurele, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tiberiu Relu","family":"Esanu","sequence":"additional","affiliation":[{"name":"Radiopharmaceutical Research Centre, Horia Hulubei National Institute of Physics and Nuclear Engineering, 077125 Magurele, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eugeniu","family":"Vasile","sequence":"additional","affiliation":[{"name":"Faculty of Applied Physics, National University for Science and Technology Politehnica of Bucharest, 060042 Bucharest, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrei Theodor","family":"Hotnog","sequence":"additional","affiliation":[{"name":"Applied Nuclear Physics Department, Horia Hulubei National Institute of Physics and Nuclear Engineering, Reactorului 30, P.O. Box MG-6, 077125 Magurele, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1128-8153","authenticated-orcid":false,"given":"Mihai","family":"Radu","sequence":"additional","affiliation":[{"name":"Department of Life and Environmental Physics, Horia Hulubei National Institute of Physics and Nuclear Engineering, Reactorului 30, P.O. Box MG-6, 077125 Magurele, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gennady","family":"Mytsin","sequence":"additional","affiliation":[{"name":"Laboratory of Nuclear Problems, Joint Institute for Nuclear Research, 6 Joliot-Curie Street, 141980 Dubna, Moscow Region, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0337-8757","authenticated-orcid":false,"given":"Mona","family":"Mihailescu","sequence":"additional","affiliation":[{"name":"Holographic Imaging and Processing Laboratory, Physics Department, National University for Science and Technology Politehnica of Bucharest, 060042 Bucharest, Romania"},{"name":"Centre for Research in Fundamental Sciences Applied in Engineering, National University for Science and Technology Politehnica of Bucharest, 060042 Bucharest, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0145-5176","authenticated-orcid":false,"given":"Diana Iulia","family":"Savu","sequence":"additional","affiliation":[{"name":"Department of Life and Environmental Physics, Horia Hulubei National Institute of Physics and Nuclear Engineering, Reactorului 30, P.O. 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