Deciphering the interactions between therapeutic lipidic nanoassemblies and serum components The complete mastery of the in vivo fate FIGURE 1 of nanodrugs is essential to ensure patient safety. However, in vivo studies are expensive and the complexity of the living organism does not always enables to monitor more in-depth molecular interactions. In this study, we have investigated in detail the in vitro fate of innovative lipidic nanoassemblies in biologic fluids and more precisely the interactions between those nanoassemblies and albumin, the most abundant proteic component of the blood serum. Despite a high degree of interest amongst researchers to design innovative nanosystems, only few have reached the market due to important gaps in their translation to clinic. Indeed, their behaviour in the body is still difficult to predict and in vivo tests are very expensive. There is thus a considerable interest to develop predictivein vitro tests to assess the fate RESULTS of nanoparticles in biological medium. Indeed, beyond the “traditional” pharmaceutical assessment of drug safety and The morphology and the colloidal stability of the SQAd nanoparticle efficacy, a thorough physico-chemical characterization of thesuspension was assessed by combining cryogenic transmission nanodrugs is necessary [2]. electron microscopy (cryoTEM) and small angle neutron scattering In this study, we have investigated the fate of squalene- (SANS, performed at the Institut Laüe Langevin in Grenoble). The adenosine nanoparticles (SQAd NPs), a nanodrug designed by presence of BSA (either alone or in Fetal Bovine Serum) with the a team of researchers at the Institut Galien Paris-Sud. This newSQAd nanoparticles induces a decrease of their size, suggesting formulation of adenosine was shown to enable the prolonged their disassembly (FIGURE 2). Surprisingly, while salts provoke circulation of the nucleoside in the bloodstream, thus providingaggregation of the nanoparticles leading to precipitation of the neuroprotection in mouse stroke and rat spinal cord injury suspension, the addition of proteins in the very same presence models [3]. Briefly, the adenosine was chemically conjugated of salts stabilizes the nanoparticles. to squalene, a biocompatible lipid precursor of cholesterol and the resulting bioconjugates were able to form nanoassemblies FIGURE 2 in aqueous solutions using “nanoprecipitation” technique. (FIGURE 1, top) [4]. These resulting SQAd NPs were then incubated with bovine serum albumin (BSA) and have been characterized with complementary techniques in order to analyse the interactions on each partner’s side: from the perspective of the nanoparticles, from that of the proteins but also from that of the SQAd bioconjugate monomer (FIGURE 1, bottom). Finally, we measured the thermodynamic quantities of the overall system and performed numeric simulations. 48