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2 results on '"This research was funded by the Spanish Ministry of Economy and Competitiveness (MINECO"'

1. Characterization and Therapeutic Effect of a pH Stimuli Responsive Polymeric Nanoformulation for Controlled Drug Release

Author

Maria Victoria Cano-Cortes, Rosario M. Sánchez-Martín, Jose Antonio Laz-Ruiz, Juan J. Díaz-Mochón, [Cano-Cortes,MV, Laz-Ruiz,JA, Diaz-Mochon,JJ, Sanchez-Martin,RM] GENYO, Centre for Genomics and Oncological Research, Pfizer/University of Granada/Andalusian Regional Government, PTS Granada, Granada, Spain. [Cano-Cortes,MV, Sanchez-Martin,RM] Department of Medicinal & Organic Chemistry, Excellence Research Unit of 'Chemistry Applied to Biomedicine and the Environment', Faculty of Pharmacy, University of Granada, Granada, Spain. [Cano-Cortes,MV, Sanchez-Martin,RM] Biosanitary Research Institute of Granada (ibs. GRANADA), University Hospital, Granada, Spain., and This research was funded by the Spanish Ministry of Economy and Competitiveness (MINECO), grant number BIO2016-80519 and the Health Institute Carlos III (ISCIII), grant number DTS18/00121 and the Andalusian Regional Government, grant number PAIDI-TC-PVT-PSETC-2.0.

Subjects
Drug, Polymers and Plastics, Cancer therapy, Concentración de iones de hidrógeno, media_common.quotation_subject, Covalent drug conjugation, Therapeutic nanodevice, 02 engineering and technology, Pharmacology, 01 natural sciences, Article, Polymeric nanoparticles, lcsh:QD241-441, Therapeutic index, lcsh:Organic chemistry, Anatomy::Cells::Cells, Cultured::Cell Line [Medical Subject Headings], Controlled drug deliver, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Toxicity Tests::Inhibitory Concentration 50 [Medical Subject Headings], Nanodevice, IC50, Phenomena and Processes::Chemical Phenomena::Hydrogen-Ion Concentration [Medical Subject Headings], covalent drug conjugation, Technology and Food and Beverages::Technology, Industry, and Agriculture::Manufactured Materials::Nanostructures::Nanoparticles [Medical Subject Headings], media_common, therapeutic nanodevice, Controlled drug delivery, Phenomena and Processes::Genetic Phenomena::Genetic Processes::DNA Damage [Medical Subject Headings], 010405 organic chemistry, Chemistry, Therapeutic effect, Chemicals and Drugs::Chemical Actions and Uses::Pharmacologic Actions::Therapeutic Uses::Antineoplastic Agents [Medical Subject Headings], Nanopartículas, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Therapeutics::Drug Therapy::Drug Delivery Systems::Delayed-Action Preparations [Medical Subject Headings], General Chemistry, 021001 nanoscience & nanotechnology, Controlled release, controlled drug delivery, In vitro, 0104 chemical sciences, polymeric nanoparticles, Cancer cell, Concentración 50 Inhibidora, cancer therapy, Chemicals and Drugs::Organic Chemicals::Alcohols::Glycols::Ethylene Glycols::Polyethylene Glycols [Medical Subject Headings], 0210 nano-technology
Abstract

Despite the large number of polymeric nanodelivery systems that have been recently developed, there is still room for improvement in terms of therapeutic efficiency. Most reported nanodevices for controlled release are based on drug encapsulation, which can lead to undesired drug leakage with a consequent reduction in efficacy and an increase in systemic toxicity. Herein, we present a strategy for covalent drug conjugation to the nanodevice to overcome this drawback. In particular, we characterize and evaluate an effective therapeutic polymeric PEGylated nanosystem for controlled pH-sensitive drug release on a breast cancer (MDA-MB-231) and two lung cancer (A549 and H520) cell lines. A significant reduction in the required drug dose to reach its half maximal inhibitory concentration (IC50 value) was achieved by conjugation of the drug to the nanoparticles, which leads to an improvement in the therapeutic index by increasing the efficiency. The genotoxic effect of this nanodevice in cancer cells was confirmed by nucleus histone H2AX specific immunostaining. In summary, we successfully characterized and validated a pH responsive therapeutic polymeric nanodevice in vitro for controlled anticancer drug release., Spanish Ministry of Economy and Competitiveness (MINECO) BIO2016-80519, Health Institute Carlos III (ISCIII) DTS18/00121, Andalusian Regional Government PAIDI-TC-PVT-PSETC-2.0

Published
2020

2. Ceramide chain length-dependent protein sorting into selective endoplasmic reticulum exit sites

Author

Stefano Vanni, Miyako Nakano, Misako Araki, Alejandro Cortes-Gomez, Sofia Rodriguez-Gallardo, Auxiliadora Aguilera-Romero, Valeria Zoni, Atsuko Ikeda, Sergio López, Susana Sabido-Bozo, Howard Riezman, Kazuo Kurokawa, Manuel Muñiz, Miho Waga, Kouichi Funato, Akihiko Nakano, Ana Maria Perez-Linero, Ministerio de Ciencia, Innovación y Universidades (España), Agencia Estatal de Investigación (España), Universidad de Sevilla, Japan Society for the Promotion of Science, Swiss National Science Foundation, Swiss National Supercomputing Centre, National Centres of Competence in Research (Switzerland), Ministerio de Educación, Cultura y Deporte (España), [Rodriguez-Gallardo,S, Sabido-Bozo,S, Cortes-Gomez,A, Aguilera-Romero,A, Perez-Linero,AM, Lopez,S, Muñiz,M] Department of Cell Biology, Faculty of Biology, University of Seville and Instituto de Biomedicina de Sevilla (IBiS), Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla, Seville, Spain. [Kurokawa,K, Waga,M, Nakano,A] Live Cell Super-Resolution Imaging Research Team, RIKEN Center for Advanced Photonics, Saitama, Japan. [Zoni,V, Vanni, S] Department of Biology, University of Fribourg, Fribourg, Switzerland. [Ikeda,A, Araki,M, Nakano,M, Funato,K] Graduate School of Integrated Sciences for Life, Hiroshima University, Hiroshima, Japan. [Riezman,H] NCCR Chemical Biology, Department of Biochemistry, University of Geneva, Geneva, Switzerland., This research was funded by the Spanish Ministry of Economy and Competitiveness (MINECO, grant number BFU2017-89700-P to M.M.), 'VI Own Research Plan' of the University of Seville (VIPPIT-2020-I.5 to M.M.), and Grants-in-Aid for Scientific Research from Japan Society for the Promotion of Science (JP25221103, JP17H06420, and JP18H05275 to A.N. and K. K., and JP19H02922 to M.N. and K.F.). S.V. and V.Z. acknowledge support from the Swiss National Science Foundation (grant no. 163966) and from the Swiss National Supercomputing Centre (CSCS) under project IDs s726 and s842. H.R. is supported by the Swiss National Science Foundation and the NCCR Chemical Biology (grants 184949 and 185898). This research was funded by the 'VI Own Research Plan 'of the University of Seville (VIPPIT-2020-I.5), 'V Own Research Plan' of the University of Seville (VPPI-US) contract (cofounded by the European Social Fund) to S.L., University of Seville fellowship to S.R.-G., Ministry of Education, Culture, and Sport (MECD) fellowship to S.S.-B., and contract from the University of Seville by the Youth Employment Initiative to A.C.-G., Universidad de Sevilla. Departamento de Biología Celular, Ministerio de Economía y Competitividad (MINECO). España, Swiss National Science Foundation (SNFS), and Swiss National Supercomputing Centre (CSCS)

Subjects
Vías secretorias, Endoplasmic Reticulum, medicine.disease_cause, Biochemistry, Chemicals and Drugs::Organic Chemicals::Amides::Ceramides [Medical Subject Headings], chemistry.chemical_compound, 0302 clinical medicine, Anatomy::Cells::Cellular Structures::Intracellular Space::Cytoplasm::Cytoplasmic Structures::Organelles::Endoplasmic Reticulum [Medical Subject Headings], Protein targeting, Research Articles, 0303 health sciences, Secretory Pathway, Multidisciplinary, Phenomena and Processes::Metabolic Phenomena::Metabolism::Biological Transport::Protein Transport [Medical Subject Headings], Chemistry, SciAdv r-articles, Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins [Medical Subject Headings], Compartmentalization (psychology), Lipids, Anatomy::Tissues::Membranes [Medical Subject Headings], Transmembrane protein, Cell biology, Protein Transport, Lípidos, Proteínas, Reticulum, Research Article, Anatomy::Animal Structures::Stomach, Ruminant::Reticulum [Medical Subject Headings], Ceramide, Cell signaling, Chemicals and Drugs::Lipids [Medical Subject Headings], Ceramides, Retículo endoplásmico, Chemicals and Drugs::Lipids::Glycolipids::Glycosylphosphatidylinositols [Medical Subject Headings], 03 medical and health sciences, Live cell imaging, medicine, Secretory pathway, 030304 developmental biology, Membranes, Endoplasmic reticulum, Glicosilfosfatidilinositoles, Proteins, Membrane Proteins, Membranas, Ceramidas, Glycosylphosphatidylinositol, Phenomena and Processes::Metabolic Phenomena::Metabolism::Biological Transport::Secretory Pathway [Medical Subject Headings], Phenomena and Processes::Physiological Phenomena::Physiological Processes::Homeostasis [Medical Subject Headings], 030217 neurology & neurosurgery
Abstract

Protein sorting in the secretory pathway is crucial to maintain cellular compartmentalization and homeostasis. In addition to coat-mediated sorting, the role of lipids in driving protein sorting during secretory transport is a longstanding fundamental question that still remains unanswered. Here, we conduct 3D simultaneous multicolor high-resolution live imaging to demonstrate in vivo that newly synthesized glycosylphosphatidylinositol-anchored proteins having a very long chain ceramide lipid moiety are clustered and sorted into specialized endoplasmic reticulum exit sites that are distinct from those used by transmembrane proteins. Furthermore, we show that the chain length of ceramide in the endoplasmic reticulum membrane is critical for this sorting selectivity. Our study provides the first direct in vivo evidence for lipid chain length-based protein cargo sorting into selective export sites of the secretory thway., This research was funded by the Spanish Ministry of Economy and Competitiveness (MINECO; grant number BFU2017-89700-P to M.M.), “VI Own Research Plan” of the University of Seville (VIPPIT-2020-I.5 to M.M.), and Grants-in-Aid for Scientific Research from Japan Society for the Promotion of Science (JP25221103, JP17H06420, and JP18H05275 to A.N. and K. K.; and JP19H02922 to M.N. and K.F.). S.V. and V.Z. acknowledge support from the Swiss National Science Foundation (grant no. 163966) and from the Swiss National Supercomputing Centre (CSCS) under project IDs s726 and s842. H.R. is supported by the Swiss National Science Foundation and the NCCR Chemical Biology (grants 184949 and 185898). This research was funded by the “VI Own Research Plan “of the University of Seville (VIPPIT-2020-I.5); “V Own Research Plan” of the University of Seville (VPPI-US) contract (cofounded by the European Social Fund) to S.L.; University of Seville fellowship to S.R.-G.; Ministry of Education, Culture, and Sport (MECD) fellowship to S.S.-B.; and contract from the University of Seville by the Youth Employment Initiative to A.C.-G.

Published
2020

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