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It has been shown that ATM enables the growth of mammalian adenocarcinoma stem cells, and therefore the potential benefits in cancer chemotherapy of a number of ATM inhibitors, such as KU-55933 (KU), are currently being investigated. We assayed the effects of utilizing a triphenylphosphonium-functionalized nanocarrier delivery system for KU on breast cancer cells grown either as a monolayer or in three-dimensional mammospheres. We observed that the encapsulated KU was effective against chemotherapy-resistant mammospheres of breast cancer cells, while having comparably lower cytotoxicity against adherent cells grown as monolayers. We also noted that the encapsulated KU sensitized the mammospheres to the anthracycline drug doxorubicin significantly, while having only a weak effect on adherent breast cancer cells. Our results suggest that triphenylphosphonium-functionalized drug delivery systems that contain encapsulated KU, or compounds with a similar impact, are a useful addition to chemotherapeutic treatment schemes that target proliferating cancers.<\/jats:p>","DOI":"10.3390\/cancers15051474","type":"journal-article","created":{"date-parts":[[2023,2,27]],"date-time":"2023-02-27T02:04:11Z","timestamp":1677463451000},"page":"1474","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["A Triphenylphosphonium-Functionalized Delivery System for an ATM Kinase Inhibitor That Ameliorates Doxorubicin Resistance in Breast Carcinoma Mammospheres"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3971-0398","authenticated-orcid":false,"given":"Venturina","family":"Stagni","sequence":"first","affiliation":[{"name":"Institute of Molecular Biology and Pathology, National Research Council (CNR), 00183 Rome, Italy"},{"name":"Laboratory of Cell Signaling, IRCCS, Fondazione Santa Lucia, 00179 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4271-4450","authenticated-orcid":false,"given":"Archontia","family":"Kaminari","sequence":"additional","affiliation":[{"name":"Institute of Nanoscience and Nanotechnology, NCSR \u2018\u2018Demokritos\u201d, 15310 Aghia Paraskevi, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudia","family":"Contadini","sequence":"additional","affiliation":[{"name":"Laboratory of Cell Signaling, IRCCS, Fondazione Santa Lucia, 00179 Rome, Italy"},{"name":"Department of Biology, University of Tor Vergata, 00133 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniela","family":"Baril\u00e0","sequence":"additional","affiliation":[{"name":"Laboratory of Cell Signaling, IRCCS, Fondazione Santa Lucia, 00179 Rome, Italy"},{"name":"Department of Biology, University of Tor Vergata, 00133 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4249-9802","authenticated-orcid":false,"given":"Rosario Luigi","family":"Sessa","sequence":"additional","affiliation":[{"name":"Institute of Molecular Biology and Pathology, National Research Council (CNR), 00183 Rome, Italy"},{"name":"Laboratory of Cell Signaling, IRCCS, Fondazione Santa Lucia, 00179 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9314-2520","authenticated-orcid":false,"given":"Zili","family":"Sideratou","sequence":"additional","affiliation":[{"name":"Institute of Nanoscience and Nanotechnology, NCSR \u2018\u2018Demokritos\u201d, 15310 Aghia Paraskevi, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6245-3863","authenticated-orcid":false,"given":"Spiros A.","family":"Vlahopoulos","sequence":"additional","affiliation":[{"name":"Horemeio Research Laboratory, First Department of Paediatrics, N.K.U.A, 11527 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dimitris","family":"Tsiourvas","sequence":"additional","affiliation":[{"name":"Institute of Nanoscience and Nanotechnology, NCSR \u2018\u2018Demokritos\u201d, 15310 Aghia Paraskevi, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,2,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"629266","DOI":"10.3389\/fphar.2020.629266","article-title":"DNA Repair Pathways in Cancer Therapy and Resistance","volume":"11","author":"Li","year":"2020","journal-title":"Front. 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