Dose Rate Effects on the Selective Radiosensitization of Prostate Cells by GRPR-Targeted Gold Nanoparticles

Ana Marques; Ana Belchior; Francisco Silva; Fernanda Marques; Maria Paula Cabral Campello; Teresa Pinheiro; Pedro Santos; Luis Santos; António P. A. Matos; António Paulo; Fernanda Marques

Key information

Authors:

Ana Marques; Ana Belchior (Ana Lúcia Vital Belchior); Francisco Silva; Fernanda Marques (Fernanda Marujo Marques); Maria Paula Cabral Campello (Maria Paula Cordeiro Crespo Cabral Campello Aboim de Barros); Teresa Pinheiro; Pedro Santos (Pedro Manuel da Cunha Catalão Pires Santos); Luis Santos; António P. A. Matos; António Paulo (António Manuel Rocha Paulo); Fernanda Marques (Maria Teresa Ferreira Marques Pinheiro)

Published in

May 9, 2022

Abstract

For a while, gold nanoparticles (AuNPs) have been recognized as potential radiosensitizers in cancer radiation therapy, mainly due to their physical properties, making them appealing for medical applications. Nevertheless, the performance of AuNPs as radiosensitizers still raises important questions that need further investigation. Searching for selective prostate (PCa) radiosensitizing agents, we studied the radiosensitization capability of the target-specific AuNP-BBN in cancer versus non-cancerous prostate cells, including the evaluation of dose rate effects in comparison with non-targeted counterparts (AuNP-TDOTA). PCa cells were found to exhibit increased AuNP uptake when compared to non-tumoral ones, leading to a significant loss of cellular proliferation ability and complex DNA damage, evidenced by the occurrence of multiple micronucleus per binucleated cell, in the case of PC3 cells irradiated with 2 Gy of γ-rays, after incubation with AuNP-BBN. Remarkably, the treatment of the PC3 cells with AuNP-BBN led to a much stronger influence of the dose rate on the cellular survival upon γ-photon irradiation, as well as on their genomic instability. Overall, AuNP-BBN emerged in this study as a very promising nanotool for the efficient and selective radiosensitization of human prostate cancer PC3 cells, therefore deserving further preclinical evaluation in adequate animal models for prostate cancer radiotherapy.