Abstract
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.
Highlights
For the past decades, nanoparticles (NPs) composed of high-Z elements have been proposed to improve cancer treatments using radiation therapies [1]
Laera et al observed that the thermodynamic stability and the secondary structure of blood proteins may vary in the presence of NPs [32]
Fluorescence quenching of serum albumins by AGuIX® was associated with a dynamic process
Summary
Nanoparticles (NPs) composed of high-Z elements have been proposed to improve cancer treatments using radiation therapies [1]. Laera et al observed that the thermodynamic stability and the secondary structure of blood proteins may vary in the presence of NPs [32] They found that gold nanoparticles (AuNPs) with hydrodynamic diameter ~34 nm do not impact the structure of human serum albumin (HSA) [32]. We present a study of AGuIX® interacting with HSA This protein is the most abundant in the blood plasma [35] but it plays an important role in the regulation of the osmotic pressure and pH, as well as the transport of compounds such as fatty acids, metal ions, pharmaceuticals and metabolites. The molar ratios of nanoagents to HSA (AGuIX®:HSA) ranged from 5 to 45 NPs per protein (5:1 to 45:1) This mimics injections of 150 to 1000 mg/kg of AGuIX® corresponding to concentrations used in clinic. A slight modification of the peak intensity was observed at 192 nm
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have