Taylor Dispersion Analysis Coupled to Inductively Coupled Plasma-Mass Spectrometry for Ultrasmall Nanoparticle Size Measurement: From Drug Product to Biological Media Studies.

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.

Probing the protein corona of gold/silica nanoparticles by Taylor dispersion analysis-ICP-MS.

Despite the tremendous interest for nanoparticles (NPs) in the biomedical field, their transfer to the clinics is still hampered, in particular due to the lack of knowledge of their behaviour in a biological environment. Indeed, the protein corona formed as soon as NPs enter the bloodstream can drastically affect their properties. The use of Taylor dispersion analysis-ICP-MS as an efficient technique dedicated to metal-containing NPs was proposed to examine these NP-protein interactions and determine protein corona thicknesses in biological fluids. This method was applied on core-shell gold/silica NPs in the presence of proteins at high concentrations and serum. Protein corona around 4 nm were measured. Moreover, the versatility of the method allowed assessing the reversible/irreversible character of the interactions.

Identification of Molecular Fragments in Equilibrium with Polysiloxane Ultrasmall Nanoparticles.

During recent decades, ultrasmall inorganic nanoparticles have attracted considerable interest due to their favorable biodistribution, pharmacokinetics and theranostic properties. In particular, AGuIX nanoparticles made of polysiloxane and gadolinium chelates were successfully translated to the clinics. In an aqueous medium, these nanoparticles are in dynamic equilibrium with polysiloxane fragments due to the hydrolysis of Si-O-Si bonds. Thanks to high-performance liquid chromatography coupled with electrospray ionization mass spectrometry, all these fragments were separated and identified.

Biodegradation of metal-based ultra-small nanoparticles: A combined approach using TDA-ICP-MS and CE-ICP-MS.

The knowledge of the fate of metal-containing nanoparticles in biological media in aqueous media is of utmost importance for the future use of these promising theranostic agents for clinical applications. A methodology based on the combination of TDA-ICP-MS and CE-ICP-MS was applied to study the degradation pathway of AGuIX, a phase 2 clinical ultrasmall gadolinium-containing nanoparticle. Nanoparticle size measurements and gadolinium speciation performed in different media (phosphate buffer, urine and serum) demonstrated an accelerated dissolution of AGuIX in serum, without any release of free gadolinium for each medium.