M.A. Fortin, M. Bouchard, M. Laprise-Pelletier, S. Turgeon
Keywords: plasma electrochemistry, dielectric barrier discharge, gold nanoparticles, radioactive nanoparticles, brachytherapy
Summary:Abstract: Gold nanoparticles (Au NPs) are increasingly considered for use as radioactive sources (198Au) for prostate brachytherapy procedures -. The range of the 198Au β-particle (0.96 MeV, ~ 11 mm in soft tissue, ~ 1100 cell diameters) is sufficiently long to provide cross-fire effects of a radiation dose delivered to cells within the prostate gland, and short enough to minimize the dose to healthy peripheral tissues. However, the efficient technological transfer of 198Au NPs into clinical procedures requires the development of novel, more efficient, safer, and more compact Au NP synthesis methods. Indeed, 198Au NPs (half-life: 2.7 days) should ideally be synthesized on site (directly in the hospitals) and upon request. The preparation of NPs with current techniques comes with several manipulation steps (ligand exchange, solvent exchange, purification procedures), which represent critical radioprotection challenges. Here we report on the development of an automated plasma reactor used to synthesize 198Au-NPs based on plasma-liquid electrochemistry (Fig. 1) . In this reactor, an argon plasma is generated at the surface of an aqueous solution containing gold salts (AuCl4-) and surfactant molecules. This method yields a continuous production of stable Au NP suspensions directly in water. In only 45 minutes, a 50 mL solution containing 1 mM of AuCl4- can be reduced into NPs with a reduction yield of 99.3 ± 0.7 %. The size of the particles is tuned by using controlled amounts of dextran, a biocompatible molecule widely used in vascular injection media. A comprehensive radioactive 198Au NPs synthesis was performed and the fractions, measured by single photon emission computed tomography (SPECT). NPs were analysed in high-resolution TEM, UV-Vis, XPS and dynamic light scattering (hydrodynamic size, Figure 2). Whereas NP synthesis efficiency rates of 22% were noted in the few minutes following synthesis, NP ripening occur at room temperature, that leads to very high conversion yields within 16 hours (96%). Finally, an integrated UV-visible spectrometer is used to monitor Au NPs growth kinetics and final size, as well as the Au NP ripening effect (Figure 3: the treated chloroauric solution was left in the UV-vis spectrometer for several hours). Overall, plasma electrochemistry could enable the efficient, on-site and upon request production of 198Au NPs for a next generation of brachytherapy procedures. References:  M. K. Khan et al, Nanomedicine Nanotechnol. Biol. Med., vol. 4, no. 1, pp. 57–69, 2008.  R. Shukla et al, Proc. Natl. Acad. Sci., vol. 109, no. 31, pp. 12426–12431, 2012.  M.-A. Fortin et al, Dielectric barrier discharge plasma method and apparatus for synthesizing metal nanoparticles; PCT2015/CA051326.