Impact of gold nanoparticle size and coating on radiosensitization and generation of reactive oxygen species in cancer therapy

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 <i>via</i> 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.