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Disease-related metabolites affect protein-nanoparticle interactions


Once in biological fluids, the surface of nanoparticles (NPs) is rapidly covered with a layer of biomolecules (i.e., “protein corona”) whose composition strongly determines its biological identity, regulating interactions with biological entities including cells and the immune system, and consequently direct biological fate and pharmacokinetics of nanoparticles. We recently introduced the concept of “personalized protein corona” which refers to the formation of the different biological identity of the exact same type of NPs after being exposed to extract plasmas from individuals who have various type of diseases. As different diseases have distinct metabolome profile and metabolomes can interact with proteins, it is legitimate to hypothesize that metabolome profiles in plasma may have a capacity to, at least partially, drive the formation of personalized protein corona. To test this hypothesis, we employed a multi-scale approach composed of coarse-grained (CG) and all atom (AA) molecular dynamics (MD) simulations to probe the role of glucose and cholesterol (model metabolomes in diabetes and hypercholesterolemia patients) on the interaction of fibrinogen protein and polystyrene NP. Our results revealed that the glucose and cholesterol had the capacity to induce substantial changes on the binding site of fibrinogen to the surface of NPs. More specifically, the simulation results demonstrated that increasing the metabolite amount could change profiles of fibrinogen adsorption and replacement, what is known as Vroman effect, on the NP surface. In addition, we also found out that metabolites can substantially determine the immune triggering potency of the fibrinogen-NP complex. Our proof-of-concept outcomes further emphasize the need for the development of patient-specific NPs in a disease type-specific manner for high yielding and safe clinical applications.

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Publication details

The article was received on 21 Dec 2017, accepted on 08 Mar 2018 and first published on 08 Mar 2018

Article type: Paper
DOI: 10.1039/C7NR09502C
Citation: Nanoscale, 2018, Accepted Manuscript
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    Disease-related metabolites affect protein-nanoparticle interactions

    M. Tavakol, A. Montazeri, R. Naghdabadi, M. J. Hajipour, S. Zanganeh, G. Caracciolo and M. Mahmoudi, Nanoscale, 2018, Accepted Manuscript , DOI: 10.1039/C7NR09502C

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