ESTRO 2024 - Abstract Book

S5426

Radiobiology - Tumour biology

ESTRO 2024

2751

Digital Poster

Study on the toxicity and efficacy of multifunctional self-degradable nanoparticles in radiotherapy

Clara Maria G de Faria 1,2 , Michael Bissoli 1 , Antonello Spinelli 3 , Riccardo Vago 2 , Vincenzo Amendola 1

1 University of Padua, Department of Chemical Sciences, Padua, Italy. 2 San Raffaele Scientific Institute, Urological Research Institute, Milan, Italy. 3 San Raffaele Scientific Institute, Experimental Imaging Center, Milan, Italy

Purpose/Objective:

Nanomedicine is a rapidly developing field due to its great potential to overcome long known challenges in the diagnosis, monitoring, control, prevention, and treatment of diseases. They can be designed as drug-delivery vehicles, contrast agents, and diagnostic devices, providing interesting features in the interaction with biomedical systems, such as the precise delivery of drugs. Gold and gold-iron alloy nanoparticles (NPs) are two examples of nanomaterials with favourable features for use in nanomedicine. Gold NPs, on one hand, have been studied extensively in the last decades due to its many advantages, but the concern about its persistence in organs for long times after administration is a challenge. However, its conjugation with iron can overcome this limitation by becoming a self degradable system. This feature was recently reported in gold-iron alloys obtained by laser ablation in liquid (LAL). In this study we investigated the potential of such systems as contrast agents for computed tomography (CT) and magnetic resonance imaging (MRI), its efficacy in enhancing radiation effects in tumours while maintaining a tolerable toxicity. Our goal is to provide more localised and precise dose deposition within tumours and greater sparing of adjacent normal tissues by image-guided radiation therapy and integration of MRI with treatment planning and its spontaneous size reduction and biodegradation in the physiological environment after use allows clearance from the body on the short/medium term.

Material/Methods:

The alloys were characterised in terms of their physico-chemical properties prior to the biological experiments. Formulations of different gold-iron proportions were tested (90/10, 25/75, 100/0) with different coatings. PC3 cell line was used as a prostate cancer model while fibroblasts were used as a normal cell line control. ROS experiments were performed using DCFDA assay, CellROX reagent (ThermoFisher, C10448). The antioxidant effect of catalase, DMSO and n-acetyl cysteine were investigated in the viability and clonogenic ability after radiotherapy. Radiation experiments were performed using an X-rays preclinical irradiator (SmART, Precision XRay) at 225 kV, with a current of 13mA.

Results:

Different nanoparticles were tested in prostate cancer and normal cells (fibroblasts and embryonic kidney cells) in terms of toxicity, radiosensitization efficacy, ROS production and DNA damage. In Figure 1 it is shown the toxicity of NPs at 48h/72h of incubation for the AuFe 25/75 and Au NPs in all three cell lines tested. We demonstrate that even at the highest concentration tested the toxicity of AuFe 25/75 is low in fibroblasts. Interestingly, it is higher in PC3 cancer cells, reaching about 40% at 300 ⲙ g/mL.