New approach for assessing the potential toxicity of nanomaterials through the use of natural nanovesicles

Stefano FAIS, Istituto Superiore di Sanità

Growing evidence is showing that body fluids contain huge amounts of extracellular nanovesicles, or exosomes, (30-1000 nm) that are released from the great majority of human cells and organs in both normal and disease condition. Exosomes derive from the endosomal compartment of the cells and shuttle a wide array of molecules including proteins, lipids, nucleic acids and metabolites. Exosomes may interact with target cells with at least two defined mechanisms: ligand-to-receptor interaction and lipid-mediated fusion with cell plasmamembrane with the transfer of the exosome content within the interacting cell.

Exosomes have proven to exert different biological functions and recently their use as vehicle for therapeutic molecules is supported by an increasing number of preclinical studies. Due to their impressive molecule cargo exosomes are also largely investigated as disease biomarkers. Studies from our Lab. have shown that exosomes may be characterized and quantified in human body fluids through an immunocapture-based test, called EXOTEST. EXOTEST is under investigation as a potential new tool for diagnosis and prognosis of human cancers. More recently some evidence suggest that exosomes may deliver chemical drugs as well. Preliminary evidence obtained in our Lab. has shown that exosome may be uploaded with chemical drugs that may work at the same time as tracers and anti-tumor drugs, such as Acridine Orange (AO), with a potential use in theranostics of tumors.  On the basis of the skill our group has acquired on the clinical application of exosomes our tasks in this project will be:  (i) to test the possibility that exosomes released by normal human macrophages may deliver nanomaterials (e.g. titanium); (ii) that exosomes purified from the plasma of human subjects transplanted with nanoparticles-structured prosthesis will contain the nanomateriali under investigation. The results will be of great importance for the setting up of new approaches aimed at evaluating the risk due to the chronic exposure to nanomaterials.  The final purpose will be to provide a more reliable quantitative in vivo determination of nanomaterials in human body fluids to better define the exposure risk and the toxicology potential. Lastly, our study will provide new information on the preferential ways our body exploits to eliminate nanomaterials that are progressively released by the implanted prosthesis.

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