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How do surface properties of nanoparticles influence their diffusion in the extracellular matrix? A model study in Matrigel using polymer-grafted nanoparticles

Marine Le Goas 1 Fabienne Testard 2 Olivier Taché 2 Nabila Debou 1 Béatrice Cambien 3 Géraldine Carrot 1 Jean-Philippe Renault 2
1 LICSEN - Laboratoire Innovation en Chimie des Surfaces et NanoSciences
NIMBE UMR 3685 - Nanosciences et Innovation pour les Matériaux, la Biomédecine et l'Energie (ex SIS2M)
2 LIONS - Laboratoire Interdisciplinaire sur l'Organisation Nanométrique et Supramoléculaire
NIMBE UMR 3685 - Nanosciences et Innovation pour les Matériaux, la Biomédecine et l'Energie (ex SIS2M)
3 TIRO - UMR E4320 - Transporteurs en Imagerie et Radiothérapie en Oncologie
SHFJ - Service Hospitalier Frédéric Joliot, TIRO-MATOs - UMR E4320 : UMR E4320
Abstract : Diffusion of nanomedicines inside the extracellular matrix (ECM) has been identified as a key factor to achieve homogeneous distribution and therefore therapeutic efficacy. Here, we sought to determine the impact of nanoparticles surface properties on their ability to diffuse in the ECM. As model nano-objects, we used a library of gold nanoparticles grafted with a versatile polymethacrylate corona which enabled to modify the surface properties. To accurately recreate the features of native ECM, diffusion studies were carried out in a tumor-derived gel (Matrigel®). We developed two methods to evaluate the diffusion ability of NPs inside this model gel: an easy to implement one based on optical monitoring and another one using small-angle X-ray scattering (SAXS) measurements. Both enabled to determine the diffusion coefficients of NPs and compare the influence of their various surface properties, while the SAXS technique also allowed to monitor the NPs structure as they diffused inside the gel. Positive charges and hydrophobicity were found to particularly hinder diffusion, and the different results suggested on the whole the presence of NPs-matrix interactions, therefore underlying the importance of the ECM model. The accuracy of the tumor-derived gels used in this study was evidenced by in vivo experiments involving intratumoral injections of NPs on mice, which showed that diffusion patterns in the peripheral tumor tissues were quite similar to the ones obtained within the chosen ECM model.
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https://hal-cea.archives-ouvertes.fr/cea-02914945
Contributor : Serge Palacin <>
Submitted on : Thursday, August 13, 2020 - 8:33:21 AM
Last modification on : Monday, October 12, 2020 - 10:46:07 AM

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Marine Le Goas, Fabienne Testard, Olivier Taché, Nabila Debou, Béatrice Cambien, et al.. How do surface properties of nanoparticles influence their diffusion in the extracellular matrix? A model study in Matrigel using polymer-grafted nanoparticles. Langmuir, American Chemical Society, In press, 36, pp.10460-10470. ⟨10.1021/acs.langmuir.0c01624⟩. ⟨cea-02914945⟩

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