The In Vivo Radiosensitizing Effect of Gold Nanoparticles Based MRI Contrast Agents

Abstract

Owing to the high atomic number (Z) of gold element, the gold nanoparticles appear as very promising radiosensitizing agents. This character can be exploited for improving the selectivity of radiotherapy. However, such an improvement is possible only if irradiation is performed when the gold content is high in the tumor and low in the surrounding healthy tissue. As a result, the beneficial action of irradiation (the eradication of the tumor) should occur while the deleterious side effects of radiotherapy should be limited by sparing the healthy tissue. The location of the radiosensitizers is therefore required to initiate the radiotherapy. Designing gold nanoparticles for monitoring their distribution by magnetic resonance imaging (MRI) is an asset due to the high resolution of MRI which permits the accurate location of particles and therefore the determination of the optimal time for the irradiation. We recently demonstrated that ultrasmall gold nanoparticles coated by gadolinium chelates (Au@DTDTPA-Gd) can be followed up by MRI after intravenous injection. Herein, Au@DTDTPA and Au@DTDTPA-Gd were prepared in order to evaluate their potential for radiosensitization. Comet assays and in vivo experiments suggest that these particles appear well suited for improving the selectivity of the radiotherapy. The dose which is used for inducing similar levels of DNA alteration is divided by two when cells are incubated with the gold nanoparticles prior to the irradiation. Moreover, the increase in the lifespan of tumor bearing rats is more important when the irradiation is performed after the injection of the gold nanoparticles. In the case of treatment of rats with a brain tumor (9L gliosarcoma, a radio-resistant tumor in a radiosensitive organ), the delay between the intravenous injection and the irradiation was determined by MRI.

Gold Nanoparticle Surface Functionalization: A Necessary Requirement in the Development of Novel Nanotherapeutics

“…Gold nanoparticles (GNPs) have been investigated as both diagnostic and therapeutic agents, utilised as potential delivery vectors, CT-contrast agents and therapeutics in their own right [5]. To date GNPs have featured in two clinical trials: CYT-6091, a GNP conjugated to polyethylene glycol (PEG) and recombinant human tumour necrosis factor alpha (rhTNF) [6], which possess both cytotoxic and immunomodulatory effects.…”

Platinum nanoparticles: an exquisite tool to overcome radioresistance

“…In a pioneering study, Hainfeld et al (2004) demonstrated that 1.9-nm gold NPs increase the effect of 250 kVp X-rays in the treatment of tumour-bearing mice. More recently, it has been shown that multimodal gold NPs improve not only the effect of ionizing radiation but also the performance of magnetic resonance imaging diagnosis (Miladi et al 2014). Other metallic compounds, such as platinum complexes and platinum NPs (PtNPs), have shown excellent properties to amplify radiation effects (Usami et al 2008; Charest et al 2010; Porcel et al 2012).…”

Thermosensitive Hydrogel Co-loaded with Gold Nanoparticles and Doxorubicin for Effective Chemoradiotherapy

“…Numerous radiosensitizers have long been investigated (3,(5)(6)(7), among which a significant effort is geared towards gold nanoparticles (AuNPs). As a high Z number (Z=79) element, AuNPs have been known to highly absorb X-rays and concentrate radiation absorption.…”

“…A recent study combined gadolinium and AuNPs for radiosensitization and magnetic resonance imaging (MRI)-based resolution, and its results showed improved radiosensitizing effect and reduced cytotoxicity (7). Another application strategy was studied by combination of AuNPs and Arg-Gly-Asp (RGD) peptides, of which the RGD was designed to antagonize the function of α(v)β(3) integrin and the AuNPs was used as a radiosensitizer (11).…”