Grupo de Sistemas Multivalentes para Nanomedicina (MS4N)
Instituto de Química Avanzada de Cataluña-Centro Superior de Investigaciones Científicas (IQAC-CSIC)
Chemical Multivalent Systems are molecules containing multiple functional groups disposed on spatial distributions that are directly associated to their skeleton/scaffold architecture. These functional groups can be modified, in a controlled manner, with diverse biomolecules, drugs or ligands. Due to this versatility, multivalent systems, and specially dendrimers, become chemical tools with great potential in areas as chemical biology and nanomedicine, such as drug delivery, diagnosis and biomaterials. Our group develop and explore the use of diverse types of chemical multivalent platforms (oligomers, dendrimers, polymers, micelles and lipid nanovesicles), being focused on dendrimers.
Design and synthesis of biocompatible DPTA-OEG based dendrimers and study their application study of their application on biomaterial functionalization, as gene-delivery systems, as imaging agents (MRI and fluorescence), among others.
Bivalent and multivalent ligand based on dendrimer platforms as pharmacological and therapeutic tools for the study of GPCR oligomerization, specifically A2AR, D2R, A1R and D1R oligomerization. Application to the development of a novel treatment for movement disorders, as Parkinson’s syndrome, spinal cord injury and restless legs syndrome
Targeted and non-targeted drug-delivery systems for mono and combination therapy for the treatment of advanced colorectal cancer and triple negative breast cancer. These systems are based on multivalent platforms, being some of them hybrids drug-dendrimer platform and micelles composed by these hybrids.
Miriam Royo Fernando Albericio
Daniel Pulido Gerardo Alexis Acosta
Fundings (last 5 years selection)
European Community Horizon 2020, NMBP-2016-2STAGE-HEALTH. “Smart multifunctional GLA-nanoformulation for Fabry disease” (SMART-4-FABRY). Proposal number: 720942-2 (2017-2020).
Ministerio de Economía y Competitividad, MINECO, Programa Estatal de I+D+i Orientada a los Retos de la Sociedad 2014. “Chemical tools to study their interaction with biological barriers and GPCR oligomers” (CHEMTOOLBOX). SAF2014-60138-R (2015-2019).
Fundació La Marató TV3 2013 focalizada en Cancer. “Personalized nanomedicine for triple negative breast cancer stem cells” (PENTRI). TV32013-133932 (2014-2017)
Ministerio de Economía y Competitividad, MINECO, Ayudas a Proyectos de Investigación Fundamental No Orientada 2011 “Multifunctional chemical entities: design, synthesis and therapeutic aplications” (MULTIFUN). SAF2011-30508-C02-01 (2012-2015).
Publications (last selection 5 years)
D. Pulido, V. Casadó-Anguera, L. Pérez-Benito, E. Moreno, A. Cordomí, A. Cortés, S. Ferré, L. Pardo, V. Casadó, M. Royo. Design of a true bivalent ligand with picomolar affinity for a G protein-coupled receptor homodimer. Journal of Medicinal Chemistry, 61, 9335-9346 (2018).
R. J. Seelbach, P. Fransen, M. Peroglio, D. Pulido, P. Lopez-Chicon, F. Duttenhoefer, S. Sauerbier, T. Freiman, P. Niemeyer, C. Semino, F. Albericio, M. Alini, M. Royo, A. Mata, D. Eglin. Multivalent dendrimers presenting spatially controlled clusters of binding epitopes in thermoresponsive hyaluronan hydrogels. Acta Biomaterialia, 10, 4340-4350 (2014).
P. Fransen, D.Pulido, C.Sevrin, C.Granfils, F.Albericio, M. Royo . High control, fast growth OEG-based dendron synthesis via a sequential process of copper free-diazo transfer and click chemistry. Macromolecules, 47, 2585–2591 (2014).
D. Pulido, F. Albericio, M. Royo. Controlling multivalency and multimodality: up to pentamodal dendritic platforms based on diethylenetriaminepentaacetic acid Cores. Organic Letters, 16, 1318−1321 (2014).
L. Simón-Gracia, D. Pulido, C. Sevrin, C. Grandfils, F. Albericio, M.Royo. Biocompatible, multifunctional, and well-defined OEG-based dendritic platforms for biomedical applications. Organic and Biomolecular Chemistry, 11, 4109-4121 (2013).
1.- Dr. Sergi Ferré, National Institute on Drug Abuse-National Institutes of Health (NIDA-NIH), Baltimore (EEUU)
2.- Dra. Olga Iranzo, Institut des Sciences Moleculaires de Marseille (ISM2-CNRS), Marsella (Francia)
3.- Dr. Tamblet Teesalu y Dra. Lorena Simón, University of Tartu, Tartu (Estonia).