Single particle ICP-MS: a tool for the characterization of gold nanoparticles in nanotheranostics applications†

Nanotheranostics aims to perform a premature and non-invasive diagnosis combined with therapy focused on the specific place where the disease is by using nanomaterials. To evaluate the ability to penetrate and retain the inorganic nanoparticles (NPs) in the cells, analytical techniques such as Single-Particle ICP-MS (SP-ICP-MS) are required to characterize these NPs. SP-ICP-MS provides not only the size distribution and concentration of NPs but also the concentration of the dissolved elements. In recent years, direct alkaline dilution of blood, serum, and urine is performed in clinical laboratories for routine analysis. This alkaline diluent is named clinical diluent and it is a mixture of ammonia, EDTA, 2-propanol, Triton X100, and purified water. In this work, a methodology to characterize AuNPs in blood and urine samples using SP-ICP-MS has been developed. Samples were directly diluted with clinical diluent before multi-quadrupole ICP-MS analysis. The effect of this clinical diluent on the behaviour and stability of AuNPs has been studied. Good stability of AuNPs was observed for both the particle size and particle concentration (<17% difference in 10 days). Moreover, analytical parameters of this method such as linearity, detection limit, accuracy, and precision in blood and urine samples were studied for both the particle size and particle concentration. Linearity was evaluated for particle size (from 10 to 100 nm) and particle concentration (from 5 × 10³ to 1 × 10⁴ NP per mL). Furthermore, recoveries between 88% and 103% for the NP concentration and between 100% and 110% for the nanoparticle size were obtained. Dissolved and gold nanoparticle detection limits have also been estimated.