RT Journal Article T1 Impact of gold nanoparticle size and coating on radiosensitization and generation of reactive oxygen species in cancer therapy A1 Loscertales, E. A1 López-Méndez, R. A1 Mateo, J. A1 Fraile Prieto, Luis Mario A1 Udías Moinelo, José Manuel A1 Espinosa, A. A1 España, S. AB Radiation therapy is a common cancer treatment but often damages surrounding healthy tissues, leading to unwanted side effects. Despite technological advancements aimed at improving targeting, minimizing exposure to normal cells remains a major challenge. High-Z nanoparticles, such as gold nanoparticles (AuNPs), are being explored as nano-radiosensitizers to enhance cancer treatment through physical, biological, and chemical mechanisms. This study focuses on evaluating the chemical and biological radiosensitizing effects of AuNPs exposed to ionizing radiation (0–50 Gy), specifically their production of reactive oxygen species (ROS) and their impact on cancer cells. ROS generated by AuNPs of varying sizes and coatings were quantified using fluorescence probes for hydroxyl radicals (HO·) and singlet oxygen (1O2). The radiosensitizing effects on MDA-MB-231 cancer cells were assessed via clonogenic assays. Our results show a clear dependence of ROS production on AuNP size. Interestingly, PEG-capped AuNPs did not significantly enhance HO· production but greatly increased 1O2 production, suggesting that multiple reactive species contribute to the radiosensitization process. Clonogenic assays confirmed that PEG-capped AuNPs produced stronger radiosensitizing effects than citrate-capped AuNPs, with smaller AuNPs providing more pronounced biological effects. This study underscores the importance of conducting both chemical and biological evaluations to fully understand the radiosensitization efficacy of AuNPs. PB Royal Society of Chemistry YR 2025 FD 2025-01-09 LK https://hdl.handle.net/20.500.14352/122639 UL https://hdl.handle.net/20.500.14352/122639 LA eng NO 1 E. Loscertales, R. López-Méndez, J. Mateo, L. M. Fraile, J. M. Udias, A. Espinosa and S. España, Nanoscale Adv., 2025, 7, 1204–1214. NO "This work was funded by Spanish MCIN/AEI/10.13039/501100011033 under NANORADIOTHER project (PID2021-127033OB-C22, PID2021-127033OB-C21) and CNS2023-144689 project, as well as by Comunidad de Madrid under ASAP-CM project (S2022/BMD-7434). S. España is supported by the Ministerio de Ciencia, Innovación y Universidades under Ayudas Ramón y Cajal RYC2018-024495-I. R. López-Méndez acknowledges MICINN for FPI grant PRE2020-96246. The CNIC is supported by the Instituto de Salud Carlos III (ISCIII), the MCIN and the Pro CNIC Foundation, and is a Severo Ochoa Center of Excellence (grant CEX2020-001041-S funded by MICIN/AEI/10.13039/501100011033). IMDEA Nanociencia acknowledges the “Severo Ochoa” program for Centres of Excellence in R&D (CEX2020-001039-S)." NO Ministerio de Ciencia, Innovación y Universidades (España) NO Comunidad de Madrid NO Instituto de Salud Carlos III DS Docta Complutense RD 3 ago 2025