Roadmap to Clinical Use of Gold Nanoparticles for Radiation Sensitization

Abstract

The past decade has seen a dramatic increase in interest in the use of Gold Nanoparticles (GNPs) as radiation sensitizers for radiotherapy. This interest was initially driven by their strong absorption of ionizing radiation and the resulting ability to increase dose deposited within target volumes even at relatively low concentrations. These early observations are supported by extensive experimental validation, showing GNPs’ efficacy at sensitizing tumors in both in vitro and in vivo systems to a range of types of ionizing radiation, including kilovoltage and megavoltage X-rays as well as charged particles. Despite this experimental validation, there has been limited translation of GNP-mediated radiosensitization to a clinical setting. One of the key challenges in this area is the wide range of experimental systems that have been investigated, spanning a range of particle sizes, shapes and preparations. As a result, mechanisms of uptake and radiosensitization have remained difficult to clearly identify. This has proven a significant impediment to the identification of optimal GNP formulations which strike a balance among their radiosensitizing properties, their specificity to the tumors, their biocompatibility, and their imageability in vivo. This white paper reviews the current state of knowledge in each of the areas concerning the use of GNPs as radiosensitizers, and outlines the steps which will be required to advance GNP-enhanced radiation therapy from their current pre-clinical setting to clinical trials and eventual routine usage.

Docetaxel-titanate nanotubes enhance radiosensitivity in an androgen-independent prostate cancer model

“…This new study aims to improve the efficacy of RT even further using gold, which has a high atomic number (Z=79) and can thus amplify the photoelectric effect. 24 Obviously, the next step for the development of our gold-DTX-nanocarrier will be a new biodistribution study using later time kinetics to ensure that TiONts do not remain within healthy organs.…”

Pinhole X-ray fluorescence imaging of gadolinium and gold nanoparticles using polychromatic X-rays: a Monte Carlo study

“…[14][15][16][17][18][19][20][21] The mechanisms of the radiation sensitization effect and methodologies for characterizing such effects have also been investigated. [22][23][24] The low-energy electrons emitted from AuNPs locally deposit their energies in close proximity, which results in physical radiation dose enhancement effect. [22][23][24][25] In addition, the effects of…”

“…[22][23][24] The low-energy electrons emitted from AuNPs locally deposit their energies in close proximity, which results in physical radiation dose enhancement effect. [22][23][24][25] In addition, the effects of…”

“…22,[26][27][28][29][30][31] The dependency of radiation sensitization on the size, shape, and concentration of AuNPs has also been presented by several studies. 23,27,[32][33][34][35][36] In order to further develop the nanoparticle-enhanced radiation therapy, monitoring the biological effects and toxicity based on in vivo biodistributions and concentrations of the nanoparticles (NP) in the target and normal tissues must be carried out during preclinical studies. 23 However, due to the lack of an effective in vivo imaging tool, there has been a slow progress on further studies in this area.…”

“…23,27,[32][33][34][35][36] In order to further develop the nanoparticle-enhanced radiation therapy, monitoring the biological effects and toxicity based on in vivo biodistributions and concentrations of the nanoparticles (NP) in the target and normal tissues must be carried out during preclinical studies. 23 However, due to the lack of an effective in vivo imaging tool, there has been a slow progress on further studies in this area. 37 X-ray fluorescence (XRF) computed tomography (XFCT) is one of the promising imaging modalities for in vivo imaging.…”