Human Serum Albumin in the Presence of AGuIX Nanoagents: Structure Stabilisation without Direct Interaction

Abstract

<jats:p>The gadolinium-based nanoagent named AGuIX® is a unique radiosensitizer and contrast agent which improves the performance of radiotherapy and medical imaging. Currently tested in clinical trials, AGuIX® is administrated to patients via intravenous injection. The presence of nanoparticles in the blood stream may induce harmful effects due to undesired interactions with blood components. Thus, there is an emerging need to understand the impact of these nanoagents when meeting blood proteins. In this work, the influence of nanoagents on the structure and stability of the most abundant blood protein, human serum albumin, is presented. Synchrotron radiation circular dichroism showed that AGuIX® does not bind to the protein, even at the high ratio of 45 nanoparticles per protein at 3 mg/L. However, it increases the stability of the albumin. Isothermal thermodynamic calorimetry and fluorescence emission spectroscopy demonstrated that the effect is due to preferential hydration processes. Thus, this study confirms that intravenous injection of AGuIX® presents limited risks of perturbing the blood stream. In a wider view, the methodology developed in this work may be applied to rapidly evaluate the impact and risk of other nano-products that could come into contact with the bloodstream.</jats:p>

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

“…Interestingly, the absence of size decrease may indicate that dissolution of the particle, if any, did not occur within a short time period (<15 min). These results also support the fact that serum proteins did not interact with the USNP, as already assumed from synchrotron radiation circular dichroism on mixtures of AGuIX and HSA …”

“…These results also support the fact that serum proteins did not interact with the USNP, as already assumed from Synchrotron radiation circular dichroism on mixtures of AGuIX® and HSA. 30 Most importantly, this analytical procedure was demonstrated to be successfully applied for hydrodynamic radius determination in various complex media, where the classical DLS and TDA-UV lack specificity (see SI, Figures S7 and S8). Hence, the use of a ICP-MS detector coupled to TDA opens new perspectives since it could be easily extended not only to other classes of metallic and hybrid USNPs to determine their behavior in biological media, but also to large biomolecules, such as specifically labelled antibodies.…”

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.…”

Identification of Molecular Fragments in Equilibrium with Polysiloxane Ultrasmall Nanoparticles

“…One of the limitations of the study is the use of an aqueous medium that cannot completely mimic the more complex interactions that may arrive in a biological medium but a precedent biodegradation study performed in phosphate buffer and serum has shown a very similar electrophoretic profile for the molecular fragments in both media [ 19 ]. Moreover, AGuIX presents very limited interactions with proteins, such as human serum albumin [ 24 ], confirmed by their very fast renal elimination [ 15 , 16 ]. Altogether, these results indicate that the fragments identified in this study will certainly also be representative of the biological medium.…”