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The fate of therapeutic nanoparticles in a model biological medium: interactions with serum albumin

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HAL Id: cea-02403841

https://hal-cea.archives-ouvertes.fr/cea-02403841

Submitted on 11 Dec 2019

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The fate of therapeutic nanoparticles in a model

biological medium: interactions with serum albumin

F. Gobeaux, J. Bizeau, F. Samson, L. Marichal, I Grillo, F. Wien, S

Yesylevsky, C. Ramseyer, M. Rouquette, S Lepêtre-Mouelhi, et al.

To cite this version:

F. Gobeaux, J. Bizeau, F. Samson, L. Marichal, I Grillo, et al.. The fate of therapeutic nanoparticles in a model biological medium: interactions with serum albumin. SFNano - C’nano, Dec 2019, Dijon, France. �cea-02403841�

(2)

Thematic Session:

nanomedicine

Keywords:

nanodrug, serum albumin, interaction, complexation, disassembly

The fate of therapeutic nanoparticles in a model biological medium:

interactions with serum albumin

F. Gobeaux1*, J. Bizeau1, F. Samson1, L. Marichal1,2, I. Grillo3, F. Wien4, S. O. Yesylevsky5,6,

C. Ramseyer6, M. Rouquette7, S. Lepêtre-Mouelhi7, D. Desmaële7, P. Couvreur7, P. Guenoun1,

J-P.Renault1, F. Testard1

1. LIONS - NIMBE CEA, CNRS, Université Paris-Saclay, CEA Saclay, 91191 Gif-sur-Yvette Cedex, France 2. I2BC, JOLIOT, DRF, CEA, CNRS, Université Paris-Saclay, Gif-sur-Yvette, France

3. Institut Laue Langevin, 71 avenue des martyrs, B.P. 156, 38042 Grenoble Cedex 9, France 4. SOLEIL Synchrotron, Saint Aubin, France

5. Department of Physics of Biological Systems, Institute of Physics of the National Academy of Sciences of Ukraine, Prospect Nauky 46, 03028 Kyiv, Ukraine

6. Laboratoire Chrono Environnement UMR CNRS 6249, Université de Bourgogne Franche-Comté, 16 route de Gray, 25030 Besançon Cedex, France.

7. Institut Galien Paris-Sud, UMR 8612, CNRS, Université Paris-Sud, Université Paris-Saclay, Faculté de Pharmacie, 5 rue Jean-Baptiste Clément, F-92296 Châtenay-Malabry Cedex, France.

In the field of nanomedicine, nanostructured nanoparticles (NPs) made of self-assembling prodrugs emerged in the recent years. In particular, the squalenoylation concept has been applied to several therapeutic agents with promising results.1,2 These nanoparticles allow a high encapsulation rate of the

active principle, the protection from quick degradation, and a good control of the targeting and release. Beyond the high potential of these NPs, there is still a need for a better understanding of their evolution in biological media. The colloidal stability of the NPs, their interaction with proteins and the impact of their internal nanostructure on their efficacy are essential questions to go towards a better understanding of the mechanism of their fate in the organism (nanoparticle disassembly, targeting etc…).

We chose to investigate these questions on the particular case of Squalene-Adenosine (SQAd) nanoparticles,3 whose neuroprotective effect has already been demonstrated in murine models and

model biological media.4 From the combination of multiple techniques (neutron and x-ray scattering,

cryogenic transmission electron microscopy, circular dichroism, fluorescence spectroscopy, isothermal titration calorimetry and DFT calculations) we have investigated the interactions between the SQAd NPs and the serum albumin, one of the main proteic components of blood plasma. We show that albumin affects the colloidal stability of the nanoparticles but also partially disassembles the nanoparticles by forming SQAd-albumin complexes. Albumin should thus play a crucial role in the transport of the prodrug, while the nanoparticles would act as a circulating reservoir in the blood stream.5

References: [1] Couvreur et al. Nano Lett. 2006, 6 (11), 2544–2548. [2] Couvreur et al. Small 2008, 4 (2), 247–253. [3] Rouquette M. et al, J Drug Target. 2019, DOI: 10.1080/1061186X.2019.1566340 [3] Gaudin et al. Nat. Nanotechnol. 2014, 9 (12), 1054–1062. [4] Gobeaux et al, submitted

This project (“Nanoprotection”) is supported by public funding supervised by the French National Agency Research (ANR) in the framework of the 'Investissements d'Avenir' program (Labex NanoSaclay, reference: ANR-10-LABX-0035).

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