The research interests of Barbara La Ferla's group at the Department of Biotechnology and Biosciences of the University of Milano-Bicocca is mainly focused on organic/medicinal chemistry with an emphasis on glycomimetics as new pharmacological lead compounds, and glyco-nanoparticles as novel medical devices for drug delivery. Projects are developed in a multidisciplinary environment, and in collaboration with biochemist, biologist and pharmacologist.
-Development of polymeric targeted drug delivery/diagnostic systems
-New 3D matrices for cell tissue engeneering
-Medicinal chemistry: development of new therapeutic agents (enzymatic inhibitors/modulators)/molecular tools for the treatment of different pathologies among which cancer, inflammatory diseases, neurodegenerative diseases, rare pathologies such as lysosomal storage diseases.
-Food supplements: development of probiotic delivery systems.
Study of the Role of the Hexosamine Biosynthetic Pathway in Cancer by means of Chemical Molecular Tools (coll. Prof. Chiaradonna BTBS)
Design and synthesis of molecular tools as modulators of the hexosamine biosynthetic pathway. In particular we focus on the inhibition of AGM1. In this project we design and synthesize glycomimetics analogues of N-acetylglucosamine-6-phosphate, the natural substrate of the enzyme AGM1. We have already identified a potent lead compound able to reduce tumor growth in vivo and are working on second generation derivatives of the lead.
Synthesis of new iminosugars as pharmacological chaperones for the treatment of mucopolysaccharidosis, and of multivalent iminosugar systems for other LSD (prof. Vito Ferro, Brisbane, Australia, Prof Tanja Wrodnigg, Graz, Austria)
Design and synthesis of iminosugars analogues of L-iduronic acid as possible pharmacological chaperones for the rescue of L-iduronidase (IDUA).
Cellulose Nanocrystals (CNCs): cellulose based nanoparticles (coll. Dr. Luca Zoia (DISAT), Prof. Patrizia Di Gennaro (BTBS), Dr. Paolo Bigini (Mario negri Institute
We are developing CNCs are drug delivery systems able to target bones, as antibacterial agents.
PLGA Nanoparticles surface decorated with Glyco-and Glycodendrimer for targeted drug delivery (Coll Prof. Paola Allavena Istituto di ricerca Humanitas).
Nowadays, surface functionalized nanoparticles (NPs) are gaining great importance in the biomedical field due to the emerging role of nanomedicine. Nanotechnology is orienteering towards the development of nano-medical devices as drug delivery and diagnostic systems with improved properties and reduced side effects if compared to traditional medicine. PLGA NPs presenting carbohydrate surface decoration for specific tissue targeting; cytotoxic drug encapsulation and fluorescently labelled. The present work consists on the preparation of biocompatible, surface decorated and drug loaded PLGA-NPs for tumor targeting and treatment.
ANTIAMILOIDOGENIC COMPOUNDS for Alzheimer's Disease (FP VII PROGRAM: CP-IP 212043-2 NAD)
In the research group we developed Glycofused tricyclic compounds as ligands able to interact with amyloid beta-peptides and to interfere with their aggregation into plaques, which represent one of the hallmarks of Alzheimer's Disease
C-GLYCOSIDES AS ANTIINFLAMMATORY AGENTS
Come dansyl with me!
A small library of naphthyl gluco derivatives was synthesised from methyl α‐D‐glucopyranoside without protection/deprotection steps. One library member, dansyl C‐glucoside 5, showed an extraordinary anti‐inflammatory activity, protecting 100 % of mice from sepsis at a dose of 25 μg kg−1.
ARSENICAL C-GLYCOSIDES AS ANTITUMORAL AGENTS
C‐Glucoside derivatives covalently linked to the arsenic atom in different oxidation states have been synthesized. The C‐glucoside conjugated to the phenyldithioarsolan group, showed promising antiproliferative activity on human neuroblastoma cells (SK‐N‐BE).
-“PLGA based nanoparticles for the monocyte-mediated anti-tumor drug delivery system”. P Allavena, A Palmioli, R. Avigni, M. Sironi, B. La Ferla*, A. Maeda* Journal of Biomedical Nanotechnology 2019 in press.
-“Glycofunctionalization of Poly(lactic-co-glycolic acid) Polymers: Building Blocks for the Generation of Defined Sugar-Coated Nanoparticles”. A Palmioli, B. La Ferla*. Organic Letters 2018, 20(12), 3509-3512.
-"Cellulose Nano Crystals as Effective Inhibitors of host cell bacteria adhesion”. G. D’Orazio, L. Munizza, J. Zampolli, M. Forcella, L. Zoia, P. Fusi, P. Di Gennaro, B. La Ferla.* J. Material Chem. B., 2017, 5, 7018-7020.
-“Inhibition of the Hexosamine Biosynthetic Pathway by targeting PGM3 causes breast cancer growth arrest and apoptosis.” F. Ricciardiello, G. Votta, R. Palorini, I. Raccagni, L. Brunelli, A. Paiotta, F. Tinelli, G. D'Orazio, S. Valtorta, L. De Gioia, R. Pastorelli, R. M. Moresco, B. La Ferla, F. Chiaradonna. Cell death and disease, 2018, 9(3), 377.
Design and synthesis of small molecules (not commercially available). Functionalised carbohydrates for derivatization of targeting devices - biomaterials – nanoparticles. Development of conjugation and bioconjugation systems. Identification and characterization of organic impurities