C. THERANOSTIC: ON A CHIP DEVICES FOR PERSONALIZED MEDICINE AND NOVEL THERAPEUTHIC TOOLS
1) Molecular diagnostics.
Contact person:
Marco Cecchini
Here we develop lab on chip devices for ultrasensitive detection of biomarkers such as proteins or mini RNAs secreted by diseased cells. These devices use the optical readout of plasmonic resonance, or they measure the resonance of acoustic waves within a functionalized cavity. These studies include multi scale atomistic simulation of the sensor-ligand interaction synergically coupled to experiments, necessary for the optimization of the detectors. These devices couple advanced microfluidic architectures for sample handling and preparation and multiple sensing blocks based on optical (surface plasmon resonance-SPR devices) or electrical (surface acoustic wave-SAW resonators) read-out. Functionalization or the sensitive areas with highly specific probes determines the selective binding of biomarkers, with the shift of the SPR or SAW cavity resonance. These platforms enable real-time, ultrasensitive detection of multiple biomarkers in a variety of body fluids for biomedical applications, such as diagnostics and prognostics, point-of-care health monitoring and personalized treatment.
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Upper pannel: Confocal microscopy images of Schwann cells on flat, RLD and RHD nano-rippled polyethylene terephthalate (PET) stained for S100 (green) and nuclei (blue). Scale bar: 100 μm. Arrows indicate the nano-ripple direction. Lowe panel: SC morphological characterization: cell area and aspect ratio for the different substrates. Cell angular distribution for the different patterns.
C. Masciullo, R. Dell'Anna, I. Tonazzini, R. Böettger, G. Pepponi, and M. Cecchini, Hierarchical thermoplastic rippled nanostructures regulate Schwann cell adhesion, morphology and spatial organization, Nanoscale, 9, 14861 (2017)
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2) Modelling of surface interactions and molecular sensing.
Contact person:
Giorgia Brancolini
A crucial element for the development of sensors on-chip is the functionalization of the sensitive element through highly specific probes for the species to be detected. Our strategy for the design of molecular diagnostic devices is driven by computational models to describe the interaction between biomolecules and surfaces, and between probe and target molecule. The theoretical / computational activities dedicated to the study of protein-surface interactions include the derivation of Force Fields Parameters for differently functionalized surfaces (or nanoparticles). Due to their chemical inertness and unique optical properties the noble metals, gold and silver, are the most commonly used metals employed as probes or sensors in these techniques and they have been the subject of many computational studies in the group. Our multi-scale computational approach combines rigid docking and enhanced sampling molecular dynamics (e.g. T-TEMD) allowing the reduction of the number of possible initial orientations, the evaluation of the stability of each orientation with MD simulations and the observation of the dynamics of adsorption in detail for the description and prediction of the mutual interaction between a given protein and a given inorganic surface.
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Protein-NP simulations. A: Representative conformations of the N6 monomer in solution (top) and adsorbed on a surface representing a Cit-AuNP (bottom): computational outcome is compatible with NMR intensity reduction. B: Representative conformations of the D76N dimer in solution (top) and adsorbed on Cit-AuNP; adsorption leads to complete dissociation of the dimeric adducts present in solution. C: Conceptual scheme of the studied systems.
G. Brancolini, M. Maschio, C. Cantarutti, A. Corazza, F. Fogolari, S. Corni, G. Esposito, Citrate stabilized Gold Nanoparticles interfere with Amyloid Fibril formation: D76N and DN6 Variants, Nanoscale, 10, 4793 (2018)
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3) Antimicrobial Photodynamic Therapy (PDT).
Contact person:
Antonella Sgarbossa
This research line joins photonics and photobiology for the realization of innovative light sources to perform antibacterial photodynamic therapy (PDT) against Helicobacter pylori (Hp), one of the most diffused infective agents in humans at a worldwide level. To overcome the problem of antibiotic resistance, we propose the use of PDT based on the presence of Hp endogenous compounds (porphyrins): if appropriately excited by visible light, porphyrins initiate photo-reactions leading to the formation of reactive oxygen species (ROS) eventually causing bacterium death.
4) Enzyme replacement therapy for lysosomal storage disorders.
Contact person:
Marco Cecchini
Lysosomal storage diseases (LSDs) are a group of approximately 50 rare inherited metabolic disorders that result from defects in lysosomal function. In particular, galactosylceramidase (GALC) enzymatic deficiency leads to the accumulation of a cytotoxic sphingolipid (the galactosylsphingosine, or psychosine, PSY) in the central and peripheral nervous system, causing demyelination and premature death generally within 2 years from birth. Here, we are developing a nanotechnology based therapeutic approach based on nanovectors for actively transporting the functional enzyme into the nervous system cell lysosomes, to correct the deficiency and prevent the build-up of high PSY concentration in the brain. This approach, here introduced for this specific disease, is potentially compatible with a large spectrum of LSDs.