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This study investigates the radiosensitizing potential of the metallacarborane Fe\/57Fe-ferrabisdicarbollide in SK-BR-3 and MDA-MB-231 breast cancer cells, using two distinct gamma-photon sources: high-dose 60Co (2.08 Gy) and low-dose 57Co (37.55 mGy, 57Fe M\u00f6ssbauer effect). Methods: We evaluated cell viability and survival in 2D monolayer and 3D spheroid cultures, as well as the mechanism of cell death (ROS production, apoptosis or necrosis). Computational dosimetry was used to calculate the average absorbed dose. Results: In 2D models, both radiation sources induced reduced viability and increased ROS, with distinct cell death patterns dependent on the source (apoptosis or necrosis). Comparing 2D and 3D MDA-MB-231 models revealed that spheroid survival was significantly more impaired. The low-dose 57Co source caused a significant radiosensitization in MDA-MB-231 spheroids, dramatically impacting viability and survival. This effect is attributed to the M\u00f6ssbauer effect, where the resonant absorption of 14.41 keV radiation by 57Fe leads to a massive, localized dose enhancement. The subsequent cascade of Auger and conversion electrons (local high LET) caused significantly greater cellular damage than sparse photon radiation. Conclusions: Fe\/57Fe-ferrabisdicarbollide demonstrates a potent radiosensitizing effect depending on the cell model and the radiation source used. Crucially, the observed radiosensitization allows for the development of a new, more efficient cancer radiotherapy approach that can achieve therapeutic efficacy using a significantly lower radiation dose to the patient. This paves the way for safer and better-tolerated cancer treatments.<\/jats:p>","DOI":"10.3390\/pharmaceutics18020214","type":"journal-article","created":{"date-parts":[[2026,2,9]],"date-time":"2026-02-09T09:41:02Z","timestamp":1770630062000},"page":"214","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Fe\/57Fe-Metallacarboranes with Radiosensitizing Potential in Breast Cancer Cell Models: Comparative Study Between High- (60Co) and Low-Energy (57Co) Gamma Radiation Sources"],"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, Bobadela, 2695-066 Loures, Portugal"},{"name":"Departamento de Engenharia e Ci\u00eancias Nucleares (DECN), Instituto Superior T\u00e9cnico, Universidade de Lisboa, Estrada Nacional 10, Bobadela, 2695-066 Loures, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5979-1810","authenticated-orcid":false,"given":"Diogo M.","family":"Engr\u00e1cia","sequence":"additional","affiliation":[{"name":"Centro de Ci\u00eancias e Tecnologias Nucleares (C2TN), Instituto Superior T\u00e9cnico, Universidade de Lisboa, Estrada Nacional 10, Bobadela, 2695-066 Loures, 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, Bobadela, 2695-066 Loures, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6171-4099","authenticated-orcid":false,"given":"Jo\u00e3o C.","family":"Waerenborgh","sequence":"additional","affiliation":[{"name":"Departamento de Engenharia e Ci\u00eancias Nucleares (DECN), Instituto Superior T\u00e9cnico, Universidade de Lisboa, Estrada Nacional 10, Bobadela, 2695-066 Loures, Portugal"},{"name":"Centro de F\u00edsica e Engenharia de Materiais Avan\u00e7ados (CeFEMA), Instituto Superior T\u00e9cnico, Universidade de Lisboa, Av. Rovisco Pais 1, 1049-001 Lisbon, Portugal"},{"name":"Laboratory of Physics for Materials and Emergent Technologies (LaPMET), Av. Rovisco Pais 1, 1049-001 Lisbon, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6536-9875","authenticated-orcid":false,"given":"Bruno J. C.","family":"Vieira","sequence":"additional","affiliation":[{"name":"Centro de Ci\u00eancias e Tecnologias Nucleares (C2TN), Instituto Superior T\u00e9cnico, Universidade de Lisboa, Estrada Nacional 10, Bobadela, 2695-066 Loures, Portugal"},{"name":"Departamento de Engenharia e Ci\u00eancias Nucleares (DECN), Instituto Superior T\u00e9cnico, Universidade de Lisboa, Estrada Nacional 10, Bobadela, 2695-066 Loures, Portugal"},{"name":"Centro de F\u00edsica e Engenharia de Materiais Avan\u00e7ados (CeFEMA), Instituto Superior T\u00e9cnico, Universidade de Lisboa, Av. Rovisco Pais 1, 1049-001 Lisbon, Portugal"},{"name":"Laboratory of Physics for Materials and Emergent Technologies (LaPMET), Av. Rovisco Pais 1, 1049-001 Lisbon, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3363-0098","authenticated-orcid":false,"given":"Pedro","family":"Santos","sequence":"additional","affiliation":[{"name":"Centro de Ci\u00eancias e Tecnologias Nucleares (C2TN), Instituto Superior T\u00e9cnico, Universidade de Lisboa, Estrada Nacional 10, Bobadela, 2695-066 Loures, Portugal"},{"name":"Departamento de Engenharia e Ci\u00eancias Nucleares (DECN), Instituto Superior T\u00e9cnico, Universidade de Lisboa, Estrada Nacional 10, Bobadela, 2695-066 Loures, 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, Bobadela, 2695-066 Loures, 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\/0000-0001-7427-722X","authenticated-orcid":false,"given":"Miquel","family":"Nuez-Mart\u00ednez","sequence":"additional","affiliation":[{"name":"Institut de Ci\u00e8ncia de Materials de Barcelona (ICMAB-CSIC), Campus U.A.B., Bellaterra, 08193 Barcelona, Spain"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9386-0349","authenticated-orcid":false,"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\/0000-0003-0646-1687","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, Bobadela, 2695-066 Loures, Portugal"},{"name":"Departamento de Engenharia e Ci\u00eancias Nucleares (DECN), Instituto Superior T\u00e9cnico, Universidade de Lisboa, Estrada Nacional 10, Bobadela, 2695-066 Loures, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3010-2417","authenticated-orcid":false,"given":"Francesc","family":"Teixidor","sequence":"additional","affiliation":[{"name":"Institut de Ci\u00e8ncia de Materials de Barcelona (ICMAB-CSIC), Campus U.A.B., Bellaterra, 08193 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 (ICMAB-CSIC), Campus U.A.B., Bellaterra, 08193 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, Bobadela, 2695-066 Loures, Portugal"},{"name":"Departamento de Engenharia e Ci\u00eancias Nucleares (DECN), Instituto Superior T\u00e9cnico, Universidade de Lisboa, Estrada Nacional 10, Bobadela, 2695-066 Loures, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2026,2,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"3279","DOI":"10.3390\/cancers3033279","article-title":"Assessment of the Evolution of Cancer Treatment Therapies","volume":"3","author":"Arruebo","year":"2011","journal-title":"Cancers"},{"key":"ref_2","first-page":"229","article-title":"Global Cancer Statistics 2022: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries","volume":"74","author":"Bray","year":"2024","journal-title":"CA Cancer J. 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