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Cytotoxicité de nanoparticules polymériques, vecteurs de médicaments

Abstract : Nanoparticles (NPS) are more and more used in medicine, in imaging and as vector for drugs. In this case, NPs are used to lessen the toxicity of the active product. However, a possible toxicity of these carriers is seldom taken into account. In the EA3452, low molecular weight heparin (LMWH)-based NPs have been devised a mix of two polymers, polycaprolactone (PCL) and Eudragit® RS (ERS). Preliminary works has shown that these NPs preparations, obtained by either nanopreciptation or double emulsion, are cytotoxic per se. on a rat macrophage cell line, NR8383 in a dose-dependent (15 - 40 µg/mL) and time-dependent (4 - 24 h) manner which was further investigated. Electron microscopy has shown that NPs enter the cell unitarily by endocytosis. They enter the mitochondria inducing a phenomenon of mitophagy but no pictures evocating apoptosis were observed. Then, we have investigated the metabolic pathways using microchip array and quantitative RT-PCR. The pathways conducting to autophagy are activated (e.g. gene atg1611) while there is no activation of the pathways conducing to apoptosis. The alteration of the morphology of the mitochondria was associated to an underexpression of opa1. Although these results were obtained with animal cell line, and should be confirmed with human macrophages, they show that NPs have biological effects that have to be evaluated before their use in human
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https://hal.univ-lorraine.fr/tel-01746286
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  • HAL Id : tel-01746286, version 1

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Housam Eidi. Cytotoxicité de nanoparticules polymériques, vecteurs de médicaments. Médecine humaine et pathologie. Université Henri Poincaré - Nancy 1, 2011. Français. ⟨NNT : 2011NAN10136⟩. ⟨tel-01746286⟩

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