RESEARCH

Nanoparticles, Quo Vadis ? Long term Fate in the body

The lifecycle of nanoparticles (NPs) in the body and potentially associated health risks raise serious concerns and logical scares. Evaluating the fate of inorganic or organic NPs help predicting the outcomes related to particles environmental exposure as well as understanding the behavior of particles that have been intentionally injected for medical purposes. Nanotoxicology aims to assess the biochemical effects caused by NPs through exposure/response assays. Reversing the point of view, the transformations inflicted by the biological environment to nanomaterials are still poorly investigated. Decreasing the size to the nanoscale endows the material with new properties but also enhances the particle’s reactivity to the local environment. NPs processing in living organisms include biotransformation, degradation, bio-assimilation, elimination or simply persistence, a variety of processes orchestrated by complex and dynamic interactions with the various biological media crossed by NPs along their odyssey in the organism. Biological interactions continuously reconfigure NPs identity and properties and initiate various mechanisms such as particle aggregation, opsonization or enzymatic attack and degradation. The main difficulty is thus to characterize in situ the complex interactions between nanoparticles and the biological milieu. The exposure to NPs raises questions on their intracellular processing, persistence and residence time within the organs. What kind of mechanisms could be employed by the cell to process NPs? When particles degrade, could the body eliminate or recycle NPs degradation products? Do we have some innate mechanisms that could protect us from potential deleterious effects generated by NPs or their degradation products? Are there some pathways of NP remediation ensured by endogenous proteins?

Our group investigates these issues for diverse types of nanoparticles ranging from the magnetic NPs with different shapes, coatings and compositions (e.g. iron oxide nanospheres, nanocubes, nanoflowers, or cobalt ferrite NPs) to gold nanoparticles, hybrid gold-iron oxide nanostructures as well as carbon nanostructures (carbon nanotubes, carbon-iron oxide hybrids).

We are developing multiscale methodologies (from whole animal to atomic scale) to study the NPs’ life-cycle and long term fate in the body. Particularly we are focusing on the time evolution of physical properties (e.g. magnetic ones), structural properties and on the NPs’ interactions with biocomponents (e.g. ferritin protein) involved in their intracellular processing. While the biotransformation of metal nanoparticles could be monitored up to one year after injection in mice, a key methodological breakthrough was achieved with the possibility to observe the degradation pathway of carbon nanotubes in real time and at the nanoscale by developing electron microscopy in liquid.

Highlights

  • News Université Paris Diderot

Degradation of a carbon nanotube filled with iron oxide nanoparticles induced by reactive oxygen species (ROS) monitored in situ by liquid-cell transmission electron microscopy. Such analysis enables to understand the role of oxidative stress mediated by macrophages in the degradation of carbon nanomaterials.

http://www.univ-paris-diderot.fr/sc/site.php?bc=recherche&np=pageActu&ref=7841

Review papers

  • Biotransformation of magnetic nanoparticles in the body. Kolosnjaj-Tabi J, Lartigue L, Javed, Luciani N, Pellegrino T, Wilhelm C, Alloyeau D, Gazeau F Nanotoday, 11:280-284 (2016)
  • In vivo degeneration and fate of inorganic nanoparticles. N Feliu, D Docter, M Heine, P del Pino, S Ashraf, J Kolosnjaj-Tabi, P Macchiarini, P Nielsen, D Alloyeau*, F Gazeau*, R Stauber*, W. J. Parak* Chemical Society Review 45:2440-2457 (2016)
    http://pubs.rsc.org/en/content/articlepdf/2016/cs/c5cs00699f

NPs exocytosis and intercellular transfer

  • Reactivity of the monocyte/macrophage system to superparamagnetic anionic nanoparticles. Luciani N, Gazeau F, Wilhelm C. Journal of Materials Chemistry. 2009 19(35) 6373-6380
  • The role of cell-released microvesicles in the intercellular transfer of magnetic nanoparticles in the monocyte/macrophage system. Luciani N, Wilhelm C, Gazeau F Biomaterials. 2010 Sep;31(27):7061-9
  • Cellular transfer of magnetic nanoparticles via cell microvesicles: impact for cell tracking by Magnetic Resonance Imaging. Silva AKA, Luciani N, Kolosnjaj-Tabi J, Wilhelm C, Gazeau F. Pharmaceutical Research, 29(5) 1392-1403 (2012)
  • Intercellular carbon nanotube translocation assessed by flow cytometry imaging. Marangon I, Boggetto N, Ménard-Moyon C, Venturelli E, Béoutis ML, Péchoux C, Luciani N, Wilhelm C, Bianco A, Gazeau F. Nano Letters 12(9):4830-7 (2012)
    Highlight in http://www.cnrs.fr/insis/recherche/actualites/transfer-intercellulaire.htm

In vivo biotransformation and degradation of iron oxide NPs

  • Degradability of superparamagnetic nanoparticles in a model of intracellular environment : follow-up of magnetic, structural and chemical properties.Lévy M, Lagarde F, Maraloiu VA, Blanchin MG, Gendron F, Wilhelm C and Gazeau F Nanotechnology. 2010 Oct 1;21(39):395103. Epub 2010 Sep 6
  • Long term in vivo biotransformation of iron-oxide nanoparticles. Lévy M, Luciani N, Alloyeau D, Elgrabli D, Deveaux V, Pechoux C, Chat S, Wang G, Vats N, Gendron F, Factor C, Lotersztajn S, Luciani A, Wilhelm C and Gazeau F Biomaterials. 2011 Jun;32(16):3988-99
  • Modeling magnetic nanoparticle dipole-dipole interactions inside living cells. M. Levy, Gazeau F, Bacri JC, Wilhelm C, Devaud M. Phys Rev B, 2011, 84, 075480-070754
  • Nanomagnetism reveals the intracellular clustering of nanoparticles in the organism. Lévy M, Wilhelm C, Luciani N, Deveaux V, Gendron F, Luciani A, Devaud M and Gazeau F Nanoscale, 2011 Oct 5;3(10):4402-10
  • Nanomagnetic sensing of blood plasma proteins interactions with iron oxide nanoparticles: Impact on macrophage uptake. L Lartigue, C Wilhelm, J Servais, C Factor, A Dencausse, JC Bacri, N Luciani and F Gazeau. ACS Nano. 6(3):2665-78 (2012)

In vivo biodegradation of iron oxide nanocubes and nanoflowers: role of particle coating and architecture

  • Biodegradation of Iron Oxide Nanocubes: High Resolution In Situ Monitoring. Lartigue L, Alloyeau D, Kolosnjaj-Tabi J, Javed Y, Guardia P, Pellegrino T, Wilhelm C, Gazeau F. ACS Nano 7 : 3939-52 (2013)
  • Biodegradation mechanisms of iron oxide monocrystalline nanoflowers and tunable shield effect of gold coating. Javed Y, Lartigue L, Hugounenq P, Vuong QL, Gossuin Y, Bazzi R, Wilhelm C, Ricolleau C, Gazeau F*, Alloyeau D.* Small. 10(16):3325-37 (2014)

Biodegradation mechanism of iron oxide monocrystalline nanoflowers and tunable shield effect of gold coating. By following the magnetic and structural transformations of multicore maghemite nanoflowers in a medium mimicking intracellular lysosomal environment, we have unraveled the mechanisms involved in the critical alterations of their hyperthermic power and their Magnetic Resonance imaging contrast effect. To overcome this harmful influence of cellular medium on the effectiveness of iron oxide-based nanomaterials, we demonstrate that the inert activity of gold nanoshells can be exploited to modulate their degradability (from Javed et al, Small. 10(16):3325-37 (2014))

The one year fate of hybrid gold/iron oxide nanostructures

  • The One Year Fate of Iron Oxide Coated Gold Nanoparticles in Mice. Kolosnjaj-Tabi J, Javed Y, Lartigue L, Volatron J, Elgrabli D, Marangon I, Pugliese G, Caron B, Figuerola A, Luciani N, Pellegrino T, Alloyeau D, Gazeau F. ACS Nano. 9(8):7925-39 (2015)

Biodegradation of iron-oxide coated gold nanoparticles in mice. Iron oxide nanocrystals are locally degraded in lysosomes of splenic and hepatic macrophages while leaving the gold particles intact. After few months in the body, degradation of the gold nanoparticles is observed as well (from Kolosnjaj-Tabi J et al ACS Nano. 9(8):7925-39 (2015)).




Liquid electron microscopy and biodegradation of carbon nanotubes

  • Unravelling Kinetic and Thermodynamic Effects on the Growth of Gold Nanoplates by Liquid Transmission Electron Microscopy. Alloyeau D, Dachraoui W, Javed Y, Belkahla H, Wang G, Lecoq H, Ammar S, Ersen O, Wisnet A, Gazeau F, Ricolleau C. Nano Lett. 15(4):2574-81 (2015)
  • Carbon Nanotube Degradation in Macrophages: Live Nanoscale Monitoring and Understanding of Biological Pathway. Elgrabli D, Dachraoui W, Ménard-Moyon C, Liu XJ, Bégin D, Bégin-Colin S, Bianco A, Gazeau F, Alloyeau D. ACS Nano, 9(10):10113-24 (2015)

Role of endogeneous protein in the bioprocessing of nanoparticles

  • Ferritin Protein Regulates the Degradation of Iron Oxide Nanoparticles . J. Volatron, F. Carn, J. Kolosnjaj-Tabi, Y. Javed, Q. L. Vuong, Y. Gossuin, C. Ménager, N. Luciani, G. Charon, M. Hémadi, D. Alloyeau*, F. Gazeau*, Small, to appear

Team