ESTRO 2024 - Abstract Book

S5370

Radiobiology - Tumour biology

ESTRO 2024

1 Faculdade de Ciências da Universidadede Lisboa, Physics, Lisbon, Portugal. 2 Faculdade de Ciências, Universidade de Lisboa, Instituto Biofísica e Engenharia Biomédica, Lisbon, Portugal. 3 Faculty of Pharmacy, Universidade de Lisboa, iMed.ULisboa, Research Institute for Medicines, Lisbon, Portugal. 4 Champalimaud Foundation, Radiotherapy, Lisbon, Portugal. 5 Faculdade de Ciências, Universidade de Lisboa, Centro de Química Estrutural, Departamento de Química e Bioquímica, Lisbon, Portugal. 6 Instituto Superior Técnico, Universidade de Lisboa, C2TN – Centro de Ciências e Tecnologias Nucleares and DECN – Departamento de Engenharia e Ciências Nucleares, Lisbon, Portugal. 7 Faculdade de Ciências, Universidade de Lisboa, Centro de Estatística e Aplicações da Universidade de Lisboa, Lisbon, Portugal

Purpose/Objective:

Introduction: Pancreatic cancer is one of the most difficult oncologic diseases with no significant improvements in treatment outcome for the past 40 years. Presently, 5-year survival rates are about 9%. The concomitant delivery of Gold Nanoparticles (AuNPs) during Radiation Therapy (RT) may represent an opportunity to improve the response to treatment for this pathology. The present work consisted of an exploratory study aiming to evaluate the in vitro potential of AuNPs during RT towards human pancreatic adenocarcinoma cells.

Material/Methods:

Materials and Methods: In this study, functionalized AuNPs with hyaluronic, and oleic acids (HAOA-AuNPs), and AuNPs with bombesin (BBN-AuNPs) were used. Atomic Force Microscopy (AFM) was used to characterize AuNPs in terms of their mean size and morphology. Pancreatic tumour cells, BxPC-3, were seeded in 96-well plates with a concentration of 4×104 cells/mL and allowed to adhere for 24h. Complete medium was then discarded, and cells were incubated with AuNPs for 4 h to allow internalization. Non-internalized AuNPs were then discarded, and 100 μL of complete medium was added to each well. Tumour cells were irradiated, in the absence or presence of AuNPs at concentrations ranging from 50 to 400 μM in a linear accelerator at a 10 cm depth. A 6 MV X-rays beam with 20x20 cm2 field size at a dose rate of 600 MU/min was used with doses ranging from 2 to 5 Gy. Loss in cell viability induced by AuNP alone, RT alone, and the combined treatment was evaluated 24, 48 and 72 h after irradiation by MTT assay. Statistical analysis on cell viability was evaluated by two-way ANOVA followed by Tukey’s multiple comparisons test.

Results:

Results: AFM showed that HAOA-AuNPs and BBN-AuNPs are spherical with a mean size of 119±28 nm and 47±8 nm, respectively.

With RT alone, only for the 72 h post-irradiation time, a statistically significant reduction in cell viability from 17-32% was obtained for cells irradiated with doses ranging from 2 to 5 Gy compared to the control (cells not irradiated), (p ≤ 0.0001). Both the treatment with HAOA-AuNPs or BBN-AuNPs alone induced cytotoxicity in a dose-dependent manner. The results of MTT assay performed 72 h post-incubation with HAOA-AuNPs alone tested at 200 and 400 μM showed a reduction statistically significant in cell viability of approximately 20±4% and 35±4%, respectively, compared to the control (p < 0.0001). No significant difference was obtained between the treatment using HAOA-AuNPs at 50 μM and the control (p = 0.26). A reduction in cell viability of 25±3% and 37±3% compared to control was achieved 72 h after incubation with BBN-AuNPs at 50 and 200 μM, respectively (p < 0.0001).