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The dynamic nature of micelles make them difficult to evaluate in terms of toxicity using a canonic dose-response approach. In our study published in Nanoscale in collaboration with Eric Doris' group (CEA Saclay), poly(diacetylene)-poly(ethylene glycol) (PDA-PEG) micelles were synthesized with variable reticulation degrees, and their intracellular fate and toxicological response was investigated in vitro on macrophages. A differential pattern was observed and revealed that non-polymerized micelles accumulate in the cell membrane and induce cell membrane permeabilization, resulting in significant toxicity, whereas polymerized, stable micelles are internalized by cells but exert no or very low toxicity. These results show the low toxicity of PDA-PEG micelles and highlight an impact of supramolecular organisation in nanotoxicology at the cellular level.
Our activities in nanomedicine and nanotoxicology for the pulmonary route was documented by "Mediachimie".
Given that some nanoparticles are known to activate the immune system, these effects should be included as a new biocompatibility criterion for new biomaterials. In a study published in Nanotoxicology in collaboration with Prof. Saadia Kerdine-Römer, we investigated the effect of surface coating of biodegradable nanoparticles, relevant as drug nanocarriers, on the potential activation of dendritic cells. Our results show that although rapidly internalized, nanoparticles are not cytotoxic. Dendritic cells still showed phenotypes and cytokine secretion profiles consistent with maturation which resulted, at least in part, from the transient intracellular activation of mitogen-activated protein kinases (MAPKs). Interestingly, nanoparticle-specific stimulation patterns were observed since their surface properties had a sensible influence on the various parameters measured.
With Elias Fattal and Said Ismail, we edited an issue of Advanced Drug Delivery Reviews addressing aptamers for therapeutics, ranging from their chemistry to their clinical applications (mainly in anticancer chemotherapy), including the mechanism of their cellular trafficking, their use as nanocarriers' targeting ligands, and the theranostic applications.
Characterization of the physicochemical interactions between exenatide and two intestinal permeation enhancers: Sodium caprate (C-10) and salcaprozate sodium (SNAC)
Twarog C, Fattal E, Noiray M, Illel B, Brayden D, Taverna M, Hillaireau H*
Int J Pharm 2022, 626, 122131, 10.1016/j.ijpharm.2022.122131
Stability, pharmacokinetics, and biodistribution in mice of the EPAC1 inhibitor (R)- CE3F4 entrapped in liposomes and lipid nanocapsules
Toussaint B, Hillaireau H, Cailleau C, Ambroise Y, Fattal, E
Int J Pharm 2021, 610, 121213, 10.1016/j.ijpharm.2021.121213
Nanotoxicology at the particle/micelle frontier: influence of core-polymerization on the intracellular distribution, cytotoxicity and genotoxicity of polydiacetylene micelles
Costamagna F, Hillaireau H, Vergnaud J, Clarisse D, Jamgotchian L, Loreau O, Denis S, Gravel E, Doris E, Fattal E
Nanoscale 2020, 12:2452-2463, 10.1039/c9nr08714a
Immunotoxicity of poly(lactic-co-glycolic acid) nanoparticles: influence of surface properties on dendritic cell activation
Barillet S, Fattal E, Mura S, Tsapis N, Pallardy M, Hillaireau H* , Kerdine-Römer S*
Nanotoxicology 2019, 13(5):606-622, 10.1080/17435390.2018.1564078
Aptamer-guided nanomedicines for anticancer drug delivery
Alshaer W, Hillaireau H*, Fattal E
Adv Drug Deliv Rev 2018, 134:122-137, 10.1016/j.addr.2018.09.011
Aptamer-guided siRNA-loaded nanomedicines for systemic gene silencing in CD-44 expressing murine triple-negative breast cancer model
Alshaer W, Hillaireau H, Vergnaud J, Mura S, Deloménie C, Sauvage F, Ismail S, Fattal E
J Control Release 2018, 271:98-106, 10.1016/j.jconrel.2017.12.022
Compared in vivo toxicity in mice of lung delivered biodegradable and non biodegradable nanoparticles
Aragao-Santiago L, Hillaireau H*, Grabowski N, Mura S, Nascimento TL, Dufort S, Coll JL, Tsapis N, Fattal E
Nanotoxicology 2016, 10(3):292-302, 10.3109/17435390.2015.1054908
Stabilization and cellular delivery of chitosan-polyphosphate nanoparticles by incorporation of iron
Giacalone G, Hillaireau H, Capiau P, Chacun H, Reynaud F, Fattal E
J Control Release 2014, 194:211-219, 10.1016/j.jconrel.2014.08.022
Nanocarriers' entry into the cell: relevance to drug delivery
Hillaireau H, Couvreur P
Cell Mol Life Sci 2009, 66(17):2873-2896, 10.1007/s00018-009-0053-z
Hervé Hillaireau is Full Professor of Pharmaceutical Technology at Université Paris-Saclay. He teaches drug delivery at the Faculty of Pharmacy and his research at Institut Galien Paris-Saclay in Elias Fattal's group relates to particle and cell engineering for therapeutic purposes, in particular:
Hervé Hillaireau - 2018