Gold nanorods: synthesis, characterization, functionalization with radiopharmaceutical and in vitro testing for application in nuclear medicine

This research focuses on the development and validation of a nano-radiosensitization strategy using gold nanorods functionalized with the TAT peptide (AuNR-TAT) to enhance the efficacy of radiotherapy. The core objective was to exploit the high atomic number of gold to increase radiation absorption and induce localized biological damage through the emission of Auger electrons. The study successfully demonstrated that the AuNR-TAT system possesses high colloidal stability and low intrinsic toxicity, making it a safe candidate for clinical applications. A central part of the investigation involved the use of physical-chemical characterization to optimize the conjugated system and Transmission Electron Microscopy (TEM) to track the intracellular fate of the nanoconstructs. The analysis revealed that while the TAT peptide facilitates high cellular uptake, the nanorods are predominantly sequestered within endolysosomal vesicles in the perinuclear region rather than translocating into the nucleus. Radiobiological assays showed a significant increase in γ-H2AX foci following irradiation, indicating enhanced DNA damage. This finding suggests that the radiosensitization is mediated by an indirect mechanism: Auger electrons generated by irradiation of AuNRs in the cytoplasm produce reactive species that migrate into the nucleus to induce complex, clustered DNA breaks. In conclusion, this work indicates that nuclear proximity could be sufficient to promote radiobiological enhancement; however, these findings should be considered as preliminary and may represent a possible proof of concept for future targeted nano-radiotherapies.