Radio-Enhancing Properties of Bimetallic Au:Pt Nanoparticles: Experimental and Theoretical Evidence

Abstract

The use of nanoparticles, in combination with ionizing radiation, is considered a promising method to improve the performance of radiation therapies. In this work, we engineered mono- and bimetallic core-shell gold–platinum nanoparticles (NPs) grafted with poly (ethylene glycol) (PEG). Their radio-enhancing properties were investigated using plasmids as bio-nanomolecular probes and gamma radiation. We found that the presence of bimetallic Au:Pt-PEG NPs increased by 90% the induction of double-strand breaks, the signature of nanosize biodamage, and the most difficult cell lesion to repair. The radio-enhancement of Au:Pt-PEG NPs were found three times higher than that of Au-PEG NPs. This effect was scavenged by 80% in the presence of dimethyl sulfoxide, demonstrating the major role of hydroxyl radicals in the damage induction. Geant4-DNA Monte Carlo simulations were used to elucidate the physical processes involved in the radio-enhancement. We predicted enhancement factors of 40% and 45% for the induction of nanosize damage, respectively, for mono- and bimetallic nanoparticles, which is attributed to secondary electron impact processes. This work contributed to a better understanding of the interplay between energy deposition and the induction of nanosize biomolecular damage, being Monte Carlo simulations a simple method to guide the synthesis of new radio-enhancing agents.

<p>Green One-Step Synthesis of Medical Nanoagents for Advanced Radiation Therapy</p>

“…85 In the presence of PtPEG NPs, the induction of nanosized damage was strongly amplified and it sharply decreased in the presence of DMSO (dotted lines). This is in agreement with previous studies performed with metal-based NPs activated by photons 26,84 or by incident ions. [27][28][29] The yields of nanosized damage in NPs free samples yield control ð Þand NPs loaded samples ðyield PtPEGNPs ) correspond to the slopes of the respective dose-response curves.…”

“…The bio-nanoprobe samples were prepared as described in our previous works with minor modifications. 26 Prior to irradiation, 500 ng of the pBR322 DNA plasmid (Sigma-Aldrich) diluted in a TE buffer solution (10 mmol.L −1 Tris-HCl (pH = 7.6) and 1 mmol.L −1 ethylenediaminetetraacetic acid (EDTA)) were incubated for 1 h with PtPEG NPs (Pt 2.42×10 −4 mol. L −1 ), or with the same amount of ultra-pure water (18.2 MΩ•cm at 25°C) in control samples.…”

“…We have actually shown that the core's size and shape, of the PEGylated metal-based NPs synthesized in pure water by our method using γ-rays, strongly depend on the chemicals nature, ie the metallic precursor (oxidation state and coordination) and stabilizer (functionality and chain length), their molar ratio and radiation dose. 26,27 In this work, the NPs obtained using an optimized PEG-OH:Pt II molar ratio of ca. 100 showed the greatest qualities such as; colloidal stability and size homogeneity.…”

“…Recently, antibody-functionalized gold and other HZ-NPs (eg Gd 2 O 3 NCs, Fe 2 O 3 NPs, Pt NDs and Bi NRs) were tested, using colon, lung and breast cancer cell models treated by protons (2150 MeV) and carbon ions (100 MeV/a.m.u, LET= 50 keV/μm). [23][24][25] Our group demonstrated that mono-and bimetallic gold, platinum as well as gadolinium-based nanoagents increase the induction of complex biodamage when photons ( 60 Co γ-rays), 26,27 proton (150 MeV) 28 or medical carbon beams (276 MeV/a.m. u) are used as ionizing radiations.…”

Advances of Non-Iron Metal Nanoparticles in Biomedicine

“…The bimetallic NPs are still under preclinical trials and, therefore, approved products are not available for clinical use. Interestingly, AuPt bimetallic NPs have been predicted for their success in therapeutic applications over monometallic NPs [26]. Very recently, AuRu NPs have been found effective against multi-drug resistant Gram-negative bacteria [27].…”