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Med. Biol."],"published-print":{"date-parts":[[2025,6,22]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>\n                  <jats:italic>Objective.<\/jats:italic> Glioblastoma multiforme (GBM) is the most diagnosed primary brain tumor in adults and remains associated with a poor prognosis due to its aggressive nature. As tumor recurrence is often observed after standard radiation treatment, the use of gold nanoparticles (AuNPs) to improve radiotherapy effectiveness has been proposed as an advanced treatment strategy for this condition. Toward this goal, we investigated the radiosensitizing potential of gastrin releasing peptide receptor (GRPR)-targeted gold nanoparticles (AuNP-BBN) carrying a bombesin peptide (BBN) in glioblastoma cells, when combined with <jats:italic>\u03b3<\/jats:italic> and x-ray radiation and in comparison with their non-targeted counterpart (AuNP-DOTA). <jats:italic>Approach.<\/jats:italic> Radiation response of U373 and U87 glioblastoma cells was studied upon exposure to Co-60 <jats:italic>\u03b3<\/jats:italic> radiation or 160 kVp x-rays and U373 cells were subjected to combined treatment with the AuNPs using the same radiation qualities. The radiobiological effects were assessed via cell viability, clonogenic survival and DNA damage assays, including the determination of the sensitization enhancement ratio (SER). To rationalize the experimental results, Monte Carlo (MC) simulations were performed based on realistic microscopy-based glioblastoma cell models. <jats:italic>Main results.<\/jats:italic> U373 and U87 cells proved to be more sensitive to x-rays than to <jats:italic>\u03b3<\/jats:italic> radiation. Incubation with AuNP-BBN caused a dose enhancement effect when combined with kilovoltage x-rays but not with Co-60 <jats:italic>\u03b3<\/jats:italic> radiation, resulting in reduced U373 cell viability, impaired proliferation and DNA damage. This outcome was not observed in cells treated with the non-targeted AuNP-DOTA, showing that the incorporation of the BBN was crucial for the radiosensitization of GRPR-positive GBM cells. MC simulated radiobiological outcomes were consistent with experimental findings. <jats:italic>Significance.<\/jats:italic> GRPR-targeted AuNP-BBN are promising nanotools for developing novel treatment strategies for GBM, acting as local and cell-specific radiotherapy enhancers. Their radiosensitizing effects were accurately predicted using an alternative MC simulation method based on realistic microscopy-based cell phantoms.<\/jats:p>","DOI":"10.1088\/1361-6560\/ade222","type":"journal-article","created":{"date-parts":[[2025,6,6]],"date-time":"2025-06-06T22:54:21Z","timestamp":1749250461000},"page":"125018","update-policy":"https:\/\/doi.org\/10.1088\/crossmark-policy","source":"Crossref","is-referenced-by-count":4,"title":["GRPR-targeted gold nanoparticles as selective radiotherapy enhancers in glioblastoma"],"prefix":"10.1088","volume":"70","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-6242-4720","authenticated-orcid":true,"given":"Ana Rita C","family":"Teixeira","sequence":"first","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0009-0003-8353-949X","authenticated-orcid":true,"given":"Joana","family":"Antunes","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4195-5810","authenticated-orcid":false,"given":"Catarina I G","family":"Pinto","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2017-3358","authenticated-orcid":true,"given":"Maria Paula Cabral","family":"Campello","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3363-0098","authenticated-orcid":true,"given":"Pedro","family":"Santos","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7497-4129","authenticated-orcid":true,"given":"C\u00e9lia M","family":"Gomes","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4145-854X","authenticated-orcid":true,"given":"Antero J","family":"Abrunhosa","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4359-493X","authenticated-orcid":false,"given":"Jorge M","family":"Sampaio","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9164-0913","authenticated-orcid":false,"given":"Ant\u00f3nio","family":"Paulo","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8054-4267","authenticated-orcid":true,"given":"Francisco","family":"Alves","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0646-1687","authenticated-orcid":true,"given":"Filipa","family":"Mendes","sequence":"additional","affiliation":[]}],"member":"266","published-online":{"date-parts":[[2025,6,20]]},"reference":[{"key":"pmbade222bib1","doi-asserted-by":"publisher","first-page":"250","DOI":"10.1016\/S0168-9002(03)01368-8","article-title":"GEANT4\u2014a simulation toolkit","volume":"506","author":"Agostinelli","year":"2003","journal-title":"Nucl. 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