{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,9]],"date-time":"2026-03-09T23:02:53Z","timestamp":1773097373273,"version":"3.50.1"},"reference-count":93,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2025,10,3]],"date-time":"2025-10-03T00:00:00Z","timestamp":1759449600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Funda\u00e7\u00e3o para a Ci\u00eancia e Tecnologia","award":["UID\/Multi\/04349\/20"],"award-info":[{"award-number":["UID\/Multi\/04349\/20"]}]},{"name":"Funda\u00e7\u00e3o para a Ci\u00eancia e Tecnologia","award":["PTDC\/QUI-QIN\/32240\/2017"],"award-info":[{"award-number":["PTDC\/QUI-QIN\/32240\/2017"]}]},{"name":"Funda\u00e7\u00e3o para a Ci\u00eancia e Tecnologia","award":["UIDP\/04565\/2020"],"award-info":[{"award-number":["UIDP\/04565\/2020"]}]},{"name":"Funda\u00e7\u00e3o para a Ci\u00eancia e Tecnologia","award":["LA\/P\/0140\/2020"],"award-info":[{"award-number":["LA\/P\/0140\/2020"]}]},{"DOI":"10.13039\/501100002809","name":"Generalitat de Catalunya","doi-asserted-by":"publisher","award":["2021 SGR 442"],"award-info":[{"award-number":["2021 SGR 442"]}],"id":[{"id":"10.13039\/501100002809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100007076","name":"AIRC","doi-asserted-by":"publisher","award":["IG 2019-ID. 23267"],"award-info":[{"award-number":["IG 2019-ID. 23267"]}],"id":[{"id":"10.13039\/501100007076","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.mdpi.com"],"crossmark-restriction":true},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>Background: Ferrabis(dicarbollide) ([o-FESAN]\u2212) in combination with proton\u2013boron fusion therapy (PBFT) or boron neutron capture therapy (BNCT) are promising alternative radiation modalities for the treatment of breast cancer. The aim of this study was to explore the underlying effects of [o-FESAN]\u2212 radio enhancement on breast cancer cells in vitro and in vivo, and to perform comparative dosimetry calculations. Methods: The cellular effects on SKBR-3 and MDA-MB-231 breast cancer cells and MDA-MB-231 xenograft-bearing nude mice induced by carrier-free [o-FESAN]\u2212 after BNCT or PBFT were evaluated following recommended protocols. Monte Carlo (MC) dosimetry calculations were performed at the cellular scale for both radiation modalities. Results: Selective retention of [o-FESAN]\u2212 within the cytoplasm and nucleus of SKBR-3 and MDA-MB-231 breast cancer cells is demonstrated. Moreover, in vivo studies with MDA-MB-231 xenograft-bearing nude mice show appreciable accumulation of [o-FESAN]\u2212 in the tumor. Both radiation modalities induce loss of cellular viability and survival. Comparative dosimetry studies between proton and neutron irradiation agree with the viability data, showing a good correlation between absorbed dose vs. cellular effects. In the case of PBFT, cell structural changes are likely due to necrosis caused by the production of reactive oxygen species (ROS). To explain the radio enhancement effects in more detail, other mechanisms should be taken into consideration. Conclusions: Our results validate the effectiveness of both PBFT and BNCT therapeutic modalities, warranting further studies on carrier-free [o-FESAN]\u2212 as a candidate drug for potential clinical translation of radio enhancers in binary radiation therapies.<\/jats:p>","DOI":"10.3390\/ph18101491","type":"journal-article","created":{"date-parts":[[2025,10,3]],"date-time":"2025-10-03T15:26:54Z","timestamp":1759505214000},"page":"1491","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Assessment of Carrier-Free Metallacarboranes for Targeted Radiation Therapies PBFT and BNCT: Comparative Cellular Effects and Dosimetry Studies with [o-FESAN]\u2212 in Breast Cancer Cells"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0511-6665","authenticated-orcid":false,"given":"Salvatore","family":"Di Maria","sequence":"first","affiliation":[{"name":"Centro de Ci\u00eancias e Tecnologias Nucleares (C2TN), Instituto Superior T\u00e9cnico, Universidade de Lisboa, Estrada Nacional 10, 2695-066 Bobadela, Portugal"},{"name":"Departamento de Engenharia e Ci\u00eancias Nucleares (DECN), Instituto Superior T\u00e9cnico, Universidade de Lisboa, Estrada Nacional 10, 2695-066 Bobadela, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1836-2603","authenticated-orcid":false,"given":"Teresa","family":"Pinheiro","sequence":"additional","affiliation":[{"name":"Departamento de Engenharia e Ci\u00eancias Nucleares (DECN), Instituto Superior T\u00e9cnico, Universidade de Lisboa, Estrada Nacional 10, 2695-066 Bobadela, Portugal"},{"name":"Instituto de Bioengenharia e Bioci\u00eancias (iBB), Instituto Superior T\u00e9cnico, Universidade de Lisboa, Av. Rovisco Pais 1, 1049-001 Lisboa, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5369-5019","authenticated-orcid":false,"given":"Lu\u00eds Cerqueira","family":"Alves","sequence":"additional","affiliation":[{"name":"Centro de Ci\u00eancias e Tecnologias Nucleares (C2TN), Instituto Superior T\u00e9cnico, Universidade de Lisboa, Estrada Nacional 10, 2695-066 Bobadela, Portugal"},{"name":"Departamento de Engenharia e Ci\u00eancias Nucleares (DECN), Instituto Superior T\u00e9cnico, Universidade de Lisboa, Estrada Nacional 10, 2695-066 Bobadela, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2138-0658","authenticated-orcid":false,"given":"Valeria","family":"Bitonto","sequence":"additional","affiliation":[{"name":"Dipartimento di Biotecnologie Molecolari e Scienze per la Salute, Centro Imaging Molecolare, via Nizza 52, 10126 Torino, Italy"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2415-128X","authenticated-orcid":false,"given":"Nicoletta","family":"Protti","sequence":"additional","affiliation":[{"name":"Dipartimento di Biotecnologie Molecolari e Scienze per la Salute, Centro Imaging Molecolare, via Nizza 52, 10126 Torino, Italy"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2998-5424","authenticated-orcid":false,"given":"Simonetta Geninatti","family":"Crich","sequence":"additional","affiliation":[{"name":"Dipartimento di Biotecnologie Molecolari e Scienze per la Salute, Centro Imaging Molecolare, via Nizza 52, 10126 Torino, Italy"}]},{"given":"Kai","family":"Nishimura","sequence":"additional","affiliation":[{"name":"School of Life Science and Engineering, Institute of Science Tokyo, 4259 Nagatsuta-cho, Midori-ku, Yokohama 226-8501, Japan"}]},{"given":"Hiroyuki","family":"Nakamura","sequence":"additional","affiliation":[{"name":"Laboratory for Chemistry and Life Science, Institute of Integrated Research, Institute of Science Tokyo, 4259 Nagatsuta-cho, Midori-ku, Yokohama 226-8501, Japan"}]},{"given":"Ant\u00f3nio P.","family":"Matos","sequence":"additional","affiliation":[{"name":"Centro de Investiga\u00e7\u00e3o Interdisciplinar Egas Moniz, Campus Universit\u00e1rio, Quinta da Granja, Monte de Caparica, 2829-511 Caparica, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4195-5810","authenticated-orcid":false,"given":"Catarina I. G.","family":"Pinto","sequence":"additional","affiliation":[{"name":"Centro de Ci\u00eancias e Tecnologias Nucleares (C2TN), Instituto Superior T\u00e9cnico, Universidade de Lisboa, Estrada Nacional 10, 2695-066 Bobadela, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0646-1687","authenticated-orcid":false,"given":"Filipa","family":"Mendes","sequence":"additional","affiliation":[{"name":"Centro de Ci\u00eancias e Tecnologias Nucleares (C2TN), Instituto Superior T\u00e9cnico, Universidade de Lisboa, Estrada Nacional 10, 2695-066 Bobadela, Portugal"},{"name":"Departamento de Engenharia e Ci\u00eancias Nucleares (DECN), Instituto Superior T\u00e9cnico, Universidade de Lisboa, Estrada Nacional 10, 2695-066 Bobadela, Portugal"}]},{"given":"Francesc","family":"Teixidor","sequence":"additional","affiliation":[{"name":"Institut de Ci\u00e8ncia de Materials de Barcelona (CSIC), Campus Universitat Aut\u00f2nomade Barcelona (UAB), 08193 Bellaterra, Barcelona, Spain"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5000-0277","authenticated-orcid":false,"given":"Clara","family":"Vi\u00f1as","sequence":"additional","affiliation":[{"name":"Institut de Ci\u00e8ncia de Materials de Barcelona (CSIC), Campus Universitat Aut\u00f2nomade Barcelona (UAB), 08193 Bellaterra, Barcelona, Spain"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8440-5299","authenticated-orcid":false,"given":"Fernanda","family":"Marques","sequence":"additional","affiliation":[{"name":"Centro de Ci\u00eancias e Tecnologias Nucleares (C2TN), Instituto Superior T\u00e9cnico, Universidade de Lisboa, Estrada Nacional 10, 2695-066 Bobadela, Portugal"},{"name":"Departamento de Engenharia e Ci\u00eancias Nucleares (DECN), Instituto Superior T\u00e9cnico, Universidade de Lisboa, Estrada Nacional 10, 2695-066 Bobadela, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2025,10,3]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"193","DOI":"10.7150\/ijms.3635","article-title":"Cancer and radiation therapy: Current advances and future directions","volume":"9","author":"Baskar","year":"2012","journal-title":"Int. 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