abstract prima parte 2016_11_16 - BtBsDay

BtBsDay 2016
2-01 Biodegradable Glyconanoparticles for Targeted Drug Delivery
Research Area: 2 - Industrial and Synthetic Biotechnology
Rana Edwards (1), Prof. Francesco Nicotra (2), Prof. Barbara La Ferla (3)
(1)(2)(3) NABBA Project- Dipartimento di Biotecnologie e Bioscienze- Università degli Studi MilanoBicocca, Piazza della Scienza, 2 20126 Milano.
[email protected]
Abstract
Biological barriers and site-targeting present some of today’s biggest challenges in drug delivery.
Recent studies have revealed a dramatic display of glycan genes, carbohydrate binding proteins,
and carbohydrate-mediated interactions overexpressed in pathological tissues such as tumor
microenvironments. Based on such findings, our research group focused its efforts on the
synthesis of non-toxic nanoparticles assembled using biodegradable copolymer PLGA [poly (lacticco-glycolic acid)] and conjugated directly with simple carbohydrates (Mannose, Galactose) for
targeted delivery. To test the multivalent effect, simple carbohydrates linked to dendrons are
synthesized and conjugated to PLGA copolymer to form glycan scaffolds. Nuclear magnetic
resonance spectroscopy (NMR) is used to characterize the covalent conjugation of the
carbohydrates/dendrons to the PLGA and their display on the surface of the assembled
nanoparticle. NMR experiments are also set up to test intermolecular interactions between
selected cancer cell lines displaying carbohydrate binding proteins and the assembled
glyconanoparticles for the analysis of carbohydrate-mediated interactions in tumor
microenvironments. Further tests on the selectivity of targeting, cellular uptake, toxicity, and the
pharmacokinetic/pharmacodynamic profile of the carriers will be conducted in-vitro on cancer
cell-lines as well as in-vivo using magnetic resonance imaging. The overall goal of the study is to
successfully assemble and characterize nanoparticles capable of targeting pathological
environments overexpressing carbohydrate receptors, and concluding whether the designed
nanocarrier system enhances the diagnostic and therapeutic properties of a selected encapsulated
drug.
This project has received funding from the European Union’s HORIZON 2020 Programme for
research, technological development and demonstration under grant agreement no. 642028
H2020-MSCA-ITN-2014