Taylor Dispersion Analysis Coupled to Inductively Coupled Plasma-Mass Spectrometry for Ultrasmall Nanoparticle Size Measurement: From Drug Product to Biological Media Studies
Lucie Labied, Paul Rocchi, Tristan Doussineau, Jérôme Randon, Olivier Tillement, François Lux, Agnès Hagège
Abstract
During past decade, special focus has been laid on ultrasmall nanoparticles for nanomedicine and eventual clinical translation. To achieve such translation, a lot of challenges have to be solved. Among them, size determination is a particularly tricky one. In this aim, we have developed a simple hyphenation between Taylor dispersion analysis and inductively coupled plasma-mass spectrometry (ICP-MS). This method was proven to allow the determination of the hydrodynamic radius of metal-containing nanoparticles, even for sizes under 5 nm, with a relative standard deviation below 10% (with a 95% confidence interval) and at low concentrations. Moreover, its specificity provides the opportunity to perform measurements in complex biological media. This was applied to the characterization of an ultrasmall gadolinium-containing nanoparticle used as a theranostic agent in cancer diseases. Hydrodynamic radii measured in urine, cerebrospinal fluid, and undiluted serum demonstrated the absence of interaction between the particle and biological compounds such as proteins.