14/06/2017

Seminar

12.00 pm, Seminar Room on the 1st Floor

Impact of the corona at the BioNano Interface

Dr. Marco Monopoli (RCSI, Ireland)

Nanoparticles (NP) are believed to radically change the way we treat diseases. Because of their small size, they can directly interact with biomolecules in an entirely different way and their behaviour in biology is still not fully understood. Once in biological fluids, NPs rapidly interact with biomolecules from the environment that firmly and rapidly adsorb to the NP surface forming the long-lived biomolecular corona.[1,2] The biomolecular corona gives a new identity to NP in the biological milieu as it has been shown to interact with cellular receptors directly. [3,4] The protein corona is derived from proteins in biological fluids, many of which are glycosylated.  We have now shown that the biomolecular corona has a strong glycosylation component and this class of biomolecules plays a dramatic role in the NP colloidal stability and firmly controls the NP biological fate. [5] In particular, in situ deglycosylation of the complex leads to partial removal of the glycans component which decreases the colloidal stability of the nanoparticle and lead to an increase of nanoparticle uptake of differentiated macrophages. Additionally, the deglycosylated corona-nanoparticles exhibit pro-inflammatory properties compared with the fully glycosylated form, suggesting the importance of glycosylation in the immunological interactions of nanoparticles. Understanding the relevance of the protein and glyco component of the corona is then of utmost importance to fully understand the interactions with cellular receptors, biocompatibility and immunological response. [5] [1] Monopoli MP, Aberg C, Salvati A, Dawson KA. Biomolecular coronas provide the biological identity of nanosized materials. Nature Nanotechnology. 2012;7:779-86 [2] Nel AE, Madler L, Velegol D,  Understanding biophysicochemical interactions at the nano–bio interface et al Nature Materials, 2009, 8, 543-557. [3] Salvati A, Pitek AS, Monopoli MP, Prapainop K, Bombelli FB, Hristov DR, Mahon E, Dawson KD. Transferrin-functionalized nanoparticles lose their targeting capabilities when a biomolecule corona adsorbs on the surface. Nat Nanotechnol. 2013;8:137-43. [4] Maiolo D, Bergese P, Mahon E, Dawson KA, Monopoli MP. Surfactant Titration of the Nanoparticle-Protein Corona. Analytical Chemistry. 2014; 86, 12055–12063 [5] Wan S, Kelly PM, Mahon E, Stockmann H, Rudd P, Caruso F, Dawson KA, Yan Y, Monopoli MP*. The "Sweet" Side of the Protein Corona: Effects of Glycosylation on Nanoparticle-Cell Interactions. ACS Nano. 2015

13/07/2017

Seminar

12.00 pm, Seminar Room on the 1st Floor

Bioresponsive Nanosized Probes for Functional MRI Applications

Priv.-Doz. Dr. Goran Angelovski. (Max Planck Institute for Biological Cybernetics MR Neuroimaging, Germany)

Bioresponsive or smart contrast agents (SCAs) can substantially improve specificity of magnetic resonance imaging (MRI) in studying processes on molecular and cellular level. These probes are capable of alternating the MR image contrast upon change in the local environment, thus reporting the occurrence of a particular physiological or pathological process. For instance, monitoring of concentration changes of ions or molecules that are involved in neuronal signaling can lead to development of new functional MRI (fMRI) methodology that allows investigation of brain activity in unprecedented fashion. To this end, we prepared and studied a series of paramagnetic and biocompatible SCAs that strongly respond to calcium ions and amino-acid neurotransmitters. Small-sized SCAs exhibited extraordinary properties in vitro, as well as in complex cellular model systems or ex vivo. Yet, we have also developed strategies to modify these SCAs and enable their coupling to diverse nanosized functional molecules. The resulting dendrimeric-, nanoparticle- or liposome-based SCAs strongly affect the MRI signal in presence of the target analyte and exhibit improved biokinetic properties. Furthermore, they possess potential for utilization in novel MRI methodologies that allow rapid monitoring of biological processes. The initial in vivo results with these SCAs are very encouraging, holding great promise for their use in molecular fMRI.