MULTIVALENT SYSTEMS FOR NANOMEDICINE
Group Leader: Miriam Royo
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 become chemical tools with great potential in areas as chemical biology and nanomedicine, such as drug delivery, diagnosis and biomaterials.
Our group explore the use of diverse types of chemical multivalent platforms (oligomers, dendrimers, polymers, micelles and lipid nanovesicles), in:
-the generation of multivalent ligands to study GPCR oligomerization; and
-the development of drug delivery systems for colorectal and breast cancer treatment, protein delivery systems for the treatment of lysosomal diseases and macromolecular compounds that have intrinsically therapeutic properties with application to central nervous system diseases.
We also explore the use of different targeting moieties (peptides, small molecules) or transporters to improve the accumulation of these delivery systems of therapeutic agents on specific cells, tissue or organs, or to facilitate the entry through biological barriers as blood brain barrier.
- Design and synthesis of biocompatible multivalent systems, as dendrimers, and the study of their applications in biomedicine and chemical biology.
- Bivalent and multivalent ligands as pharmacological tools for the study of GPCR oligomerization, specifically A2AR, D2R, A1R and D1R oligomerization. Explore their application on 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.
- Targeting moiety-cholesterol-PEG hybrids as components of lipid nanoparticles. Application to the development of a protein delivery system for Fabry’s disease.
- Transporter based on peptidomimetics or peptides with the ability to cross biological barriers, as cell membrane and blood brain barrier. Peptide and small molecule ligands as targeting moieties for different applications.
Scientific staff
Miriam Royo
Scientific Researcher
miriam.royo@iqac.csic.es
Lab people
Daniel Pulido
CIBER Researcher
daniel.pulido@iqac.csic.es
Edgar Cristóbal
Postdoctoral Researcher
edgar.cristobal@iqac.csic.es
Gerardo Acosta
CIBER Researcher
gerardo.acosta@iqac.csic.es
- Design of a true bivalent ligand with picomolar binding affinity for a G protein-coupled receptor homodimer.-
D. Pulido, V. Casadó-Anguera, L. Pérez-Benito, E. Moreno, A. Cordomi, L. López, A. Cortés, S. Ferré, L. Pardo, V. Casadó, M. Royo
Journal of Medicinal Chemistry (2018), 61, 9335-9346
- Environmental effects determine the structure of potential b-amino acid based foldamer-
F. Sussman, V. M. Sánchez-Pedregal, J. C. Estévez, R. Balo, J. Jiménez-Barbero, A. Ardá, A. Gimeno, M. Royo, M. C, Villaverde, R. J. Estévez
Chemistry European Journal (2018), 24, 10625-10629.
- Solid-phase synthesis of homodetic cyclic peptides form Fmoc-MeDbZ-resin-
M. Abdel, A.H. Shimaa, G. A. Acosta, M. Royo, A. El-Faham, B. G. de la Torre, F. Albericio
Tetrahedron Letters (2018), 59, 1779-1782.
- Stimuli-responsive functionalization strategies to spatially and temporally control surface properties: Michael vs Diels-Alder type additions.-
A.R. Kyvik, C. Luque-Corredera, D. Pulido, M. Royo, J. Veciana, J. Guasch, I. Ratera
Journal of Physical Chemistry B (2018), 122, 4481-4490.
- Development of surface modified biodegradable polymeric nanoparticles to deliver GSE24.2 peptide to cells: A promising approach for the treatment of defective telomerase disorders.-
S. P. Egusquiaguirre, C. Manguán-García, L. Pintado-Berninches, L. Iarriccio,D. Carbajo, F. Albericio, M. Royo, J. L. Pedraz, R. M. Hernández, R.Perona, M. Igartua
European Journal of Pharmaceutics and Biopharmaceutics (2015), 91, 91-102
- Facile solid-phase synthesis of head-side chain cyclothiodepsipeptides through a cyclative cleavage from MeDbz-resin-
G. A. Acosta, M. Royo, B. G. de la Torre, F. Albericio
Tetrahedron Letters (2017), 58, 2788-2791.
- Insulin-mimetic compound hexaquis (benzylammonium) decavanadate is antilipolytic in human fat cells-
C. Carpéné, S. Garcia-Vicente, M. Serrano, L. Marti, C. Belles, M. Royo, J. Galitzky, A. Zorzano, X. Testar.
World J. Diabetes (2017), 8, 143-153.
- Highly versatile polyelectrolyte complexes for improving the enzyme replacement therapy of lysosomal storage disorders-
M. Gianotti , I.Abasolo, M.Oliva, F. Andrade, N. García-Aranda, M. Melgarejo, D. Pulido, J.L. Corchero, Y. Fernández, A. Villaverde, M. Royo, M.F. García-Parajo, F. Sanz, S. Schwartz.
ACS Applied Materials & Interfaces (2016), 8, 25741-25752.
- α-Galactosidase A Loaded Nanoliposomes with Enhanced Enzymatic Activity and Intracellular Penetration-
I. Cabrera, I. Abasolo, J. L. Corchero, E. Elizondo, P. Rivera, S. Sala, M. Rivas, M. Melgarejo, D. Pulido, M. Royo, F. Albericio, A. Villaverde, M. F. García-Parajo, S. Schwartz Jr., N. Ventosa, J. Veciana
Advanced Healthcare Materials (2016), 5, 829-840.
- An immunochemical strategy based on peptidoglycan synthetic peptide epitopes to diagnose Staphylococcus aureus infections.-
C.Pastells, G. Acosta, N. Pascual, F. Albericio, M. Royo, M.-P. Marco
Analytica Chimica Acta (2015), 889, 203-211.
- Injectable hyaluronan hydrogels with peptide-binding dendrimers modulate the controlled release of BMP-2 and TGF-b1.-
R. J. Seelbach, P. Fransen, D. Pulido, M. D’Este, F. Duttenhoefer, S. Sauerbier, T. Freiman, P. Niemeyer, F. Albericio, M. Alini, M. Royo, A. Mata, D. Eglin
Macromolecular Bioscience (2015), 15, 1035-1044.
- A solid-phase combinatorial approach for indoloquinolizidinepeptides with high affinity at D1 and D2 dopamine receptors.-
A. Molero, M. Vendrell *, J. Bonaventura, J. Zachmann, L. López, L. Pardo, C. Lluis, Antoni Cortés, F. Albericio, V. Casadó, M. Royo
European Journal of Medicinal Chemistry (2015), 97-173-180.
- r1 and r1 relaxivities of dendrons based on a OEG-DTPA architecture: effect of Gd3+ placement and dendron functionalization-
P. Fransen, D. Pulido, L. Simon-Gracia, A. P. Candiota, C. Arus, F. Albericio, M. Royo*
Journal of Nanotechnology (2015), 1-9
- Gated mesoporous silica nanoparticles using a double-role circular peptide for the controlled and target-preferential release of doxorubicin in CXCR4-expressing lymphoma cells-
C. de la Torre, I. Casanova, G. Acosta, C. Coll, M. J. Moreno, F. Albericio, E. Aznar, R. Mangues*, M. Royo*, F.Sancenón, R. Martínez-Máñez*
Advanced Functional Materials (2015), 25, 687-695.
- Analogs of natural aminoacyl-tRNA synthetase inhibitors clear malaria in vivo-
E.M. Novoa, N. Camacho, A.Tor, B. Wilkinson, S. Moss, P. Marín-García, I. G. Azcárate, J. M. Bautista, A. C. Mirando, C.S. Francklyn, S. Varón, M. Royo, A. Cortés, L. Ribas de Pouplana
Proceedings of National Academy of Sciences USA (2014), 111, E5508-E5517
- Triazene as a powerful tool for solid-phase derivatization of phenylalanine containing peptides: Zygosporamide analogues as a proof of concept-
C. Torres-García, D.Pulido, F. Albericio, M. Royo*, Ernesto Nicolás*
Journal of Organic Chemistry (2014), 79,11409-11415.
- Multivalent dendrimers presenting spatially controlled clusters of binding epitopes in thermoresponsive hyaluronan hydrogels.-
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.
Acta Biomaterialia (2014), 10, 4340-4350.
- High control, fast growth OEG-based dendron synthesis via a sequential process of copper free-diazo transfer and click chemistry.-
P. Fransen, D.Pulido, C.Sevrin, C.Granfils, F.Albericio*, M. Royo*
Macromolecules (2014), 47, 2585–2591.
- Amphiphilic cationic carbosilane-PEG dendrimers: synthesis and applications in gene therapy.-
J. Sánchez-Nieves, P. Fransen, D.Pulido, R. Lorente, M. A. Muñoz-Fernández, F.Albericio, M. Royo*, R. Gómez*, F. Javier de la Mata*
European Journal of Medicinal Chemistry (2014), 31, 43-52.
- Controlling multivalency and multimodality: up to pentamodal dendritic platforms based on diethylenetriaminepentaacetic acid Cores.-
D.Pulido, F. Albericio,* M. Royo*
Organic Letters (2014), 16, 1318−1321.
