Official website: nanobiofaces.imi.hr
Project duration: 1.1. 2018. – 31.12. 2019.
Croatian project coordinator: Dr. sc. Ivana Vinković Vrček, Institute for Medical Research and Occupational Health, Zagreb, Croatia
German project coordinator: Dr. sc. Wolfgang Fritzsche, Leibniz Institute of Photonic Technology (IPHT), Germany
Granted by: DAAD-MZOS granting scheme
Institute for Medical Research and Occupational Health, Zagreb, Croatia
Abstract: Any innovations in diagnosis, therapy and disease prevention hold out the promise of major benefits to patients and, in the long term, to whole healthcare systems. Application of nanotechnology in medicine has already created substantial improvement of therapeutics, diagnostics and regenerative medicine. Nanoparticles (NPs) have an enormous potential in the medical arena as delivery vehicles, fluorescent labels, contrast agents, antimicrobial coatings, etc. At the nanosize, the surface-to-volume ratios become huge resulting in an unexpected mechanical properties and catalytic activity of NPs leading to the substantially different physico-chemical characteristics of NPs compared to macro- or micron-sized materials. Also, the similarity in size between NPs and natural biomolecules translates into an increased potential for NPs to interfere with biological systems/processes like cell membranes, biochemical pathways in cells, or even the genetic code itself. However, the current state of the art lacks fundamental understanding of the fate and transportation of NPs within human body, the ability to detect them, and the understanding of how specific exposures affect human health limits risk assessment of novel nanoproducts. The largest source of uncertainty for NPs is related to the dynamic physicochemical interactions, kinetics and thermodynamic equilibrium at the nano–bio interface. It is impossible to inevitably describe all events at this interface, but additional information on the more specific interplay of NPs with bioactive components of living cells and tissue compartments are of the highest relevance for prospective evolution of nanomedicine. In order to understand these phenomena, characterization techniques able to study this dynamics are required. It would be helpful in order to understand the influence of certain parameters (like particle composition, surface functionalization, size/shape etc) to study different particles in one experiment. This multiplexed apporach is not possible today. The proposed project aims to develop a multiplexed platform to monitor the biomolecular corona formation dynamics on an whole array of different NPs simultaneously in one experiment, using a plasmonic nanoparticle array with spectroscopic readout. Therefore, NPs of different composition/size/functionalization will be immobilized in a spot array on a glass substrate in a flow-through cell, and an imaging spectrometer readout is utilized. Dedicated microfluidic setup (flow-through cell) including computer controlled pumps will be integrated into the spectrometer setup. Assay protocolos will be set up in order to follow the protein adsorption on each of the NP spots individually. Deevelopment of his platform will allow (a) to reveal the kinetics of protein adsorption and the dependencies of various parameters, (b) to evaluate the stability and transformations of different NPs in relevant biological matrices (water, buffer media, cell culture media, human blood plasma) which can alter their chemical and/or structural nature, (c) to determine the binding activities and competitiveness of specific proteins on surfaces of NPs in relevant biological matrices, (d)- to elucidate the mechanisms of protein corona formation at the nano-bio interface. Performance of described multiplexed platform will be tested in a multi-method approach – combining sophisticated methods including fluorescence spectroscopy, mass spectrometry, electron microscopy and circular dichroism technique. As a major outcome, project will provide substantial knowledge on consequences of nano-bio interactions for the medical applications of nanomaterials.