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

Abstract

During last 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 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 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.

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

“…At tinc=0, the hydrodynamic size of the AGuIX UNSPs is similar in both types of media, illustrating their colloidal stability. Moreover, an absence of interactions with proteins in serum was noticed, as already reported in others papers [27,38,39]. Soon after dilution, a process of biodegradation occurs as asserted by the USNP size decrease.…”

“…The interface used for TDA consisted in a T-connector where the capillary outlet was inserted through and then connected to the ICP-MS. A sheath liquid (HNO3 1 mM) was added to the junction in order to compensate for the self-aspiration of the nebulizer and to allow quantification without matrix matching as described in [27]. TDA experiments were conducted with an applied mobilization pressure of 50 mbar.…”

“…TDA-ICP-MS has been successfully applied to determine an average size of the AGuIX USNPs [27]. However, a monomodal description of the AGuIX USNP is not sufficient to fully describe the degradation process that may occur in different media.…”

“…Hence, Fluorescence Correlation Spectroscopy was used for the characterization of ultrasmall fluorescent silica nanoparticles [26]. Recently we showed that Taylor Dispersion Analysis (TDA)-ICP-MS is particularly adapted for the measurement of mean hydrodynamic radii of metalcontaining particles in biological media [27]. The biodegradability of polysiloxane USNPs in diluted solutions was shown to lead to fragments composed of siloxanes of different compositions [28].…”

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

“…We recently showed that Taylor dispersion analysis hyphenation to inductively coupled plasma mass spectrometry (TDA-ICP-MS) is particularly adapted for metal-containing NP size measurements [21,22]. Furthermore, thanks to the selectivity of the technique to metals, TDA-ICP-MS allows size measurements to be performed in complex matrices, rich in proteins, whereas these measurements are often not possible by DLS.…”