Nanotechnology is one of the primary drivers of technology innovation, and it is one of the leading pillars of the six Key Enabling Technologies of Horizon 2020. Among the different application scopes of nanotechnology, its use in medicine has attracted considerable attention for its potential advances in healthcare, personalised medicine and to tackle complex issues such as the targeted and programmed delivery of drugs. The birth of nanomedicine required integration of different research field, such as nanoscience, physics, chemistry, modern pharmacy and clinical practice into a unique multidisciplinary research topic, all of which will be applied in the context of NanoCarb.
The scientific activities are organised with three Work Packages (WP):
WP1 - Nanomaterial and glycan synthesis and functionalisation
We aim to develop three sets of glyco-nanomaterials, where each of them will have the following characteristics:
- highly glycosylated NP (bottom-up approach) with sialic acid and synthetic glycans with increased negative charge for prolonged circulation time and lower degree of corona formation (stealth);
- Glyco-NPs coated with isolated and purified naturally occurring N-glycans;
- Glyco-NP with enhanced biological activity, i.e. targeting properties (coated with sialyl Lewis x (sLex) and mannose).
WP2 – Nanomaterial BioNano Interfaces
The objective is to validate the bioactivity of glycomaterials and to generate knowledge on the relation between structure and bioperformance by:
- applying proteomics, glycoprofiling and physical chemical methods to characterise the biomolecular corona formation;
- performing Systematic receptor binding studies with selected human lectins by means of Surface Plasmon Resonance, Fluorescence correlation spectroscopy, Differential Centrifugal Sedimentation and QCM on immobilised cells. The binding interaction will be assessed with and without blood proteins to evaluate the corona interference. Overall these results will provide important information for the design of strategies for glycan conjugation;
- transfering the acquired knowledge in WP2 to WP1 to optimize material design and to WP3 on application suitability.
WP3 – Nanomaterial testing in vitro and in vivo
Within this WP, we will evaluate glycomaterials in areas of nanomedine in order to develop novel types of nanomaterials by:
- defining the best suitable design of glycomaterials of having an increased circulation time, attenuated immunological recognition, increased targeting and of having a therapeutic effect;
- applying guided benchmarking of glycomaterials for selected application (in vitro assay and in vivo model of brain ischemic injury);
- fully characterised the NP transformation and behaviour in preclinical study on healthy and diseased animals.
Several diseases can be modulated by the interaction of the glycan and lectin receptors but limited therapeutic options are available as a systemic administration of the glycans will not ensure the targeting to the affected area. In particular, the interaction and the removal and scavenging of the mannose-binding proteins (MBL) and its scavenging ability will be investigated.