News

II COURSE FOR THE PERFORMANCE OF FUNCTIONS A, B AND C IN RODENTS, LAGOMORPHES, CARNIVORES, PIGS AND SMALL RUMIANTS

JUMISC has organised the II Course for the performance of functions A, B and C in rodents, lagomorphes, carnivores, pigs and small rumiants which wil take place at JUMISC from 3 February to 20 March co-Directed by D. LUIS DÁVILA GÓMEZ, Scientific Director of NANBIOSIS U22. Animal housing and DR. FRANCISCO MIGUEL SÁNCHEZ MARGALLO (Deputy Scientific Director of NANBIOSIS)

The total duration of the course is 100 hours (58 theory and 42 practice)

This course has as specific objectives to provide information and expand existing knowledge in the following aspects:
-Specific legislation regarding animal experimentation .
-Ethical considerations and the principles of replacement, reduction and refinement.
-Biology, housing, handling and care of experimental animals.
-Occupational health and safety.
-Recognition of the state of health and disease of experimental animals.
-Implications of the microbiological status of animals in the experimental process.
-Anesthesia, analgesia and basic principles of surgery.
-Realization of specific procedures with experimental animals and their practical development.
-Bloodless methods of euthanasia of animals.

Programm and inscriptions here

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A new fluorescent probe for NO

Nitric oxide is a component of the pollutant nitrogen oxides (NOx) responsible of different environmental negative effects. However, due to its physiological effects, NO has been used in different therapeutic applications. Thus, the inhaled nitric oxide (iNO) is a selective pulmonary vasodilator that finds its best applications in pediatrics, by transiently improving oxygenation in respiratory failure and persistent pulmonary hypertension. The initial recommended concentration of iNO in these treatments is 20 ppm. Higher concentrations do not increase its effectiveness and are associated with a higher incidence of methemoglobinemia and formation of nitrogen dioxide. In consequence the control of iNO concentration is of great interest.

Silvia Rodríguez-Nuévalos, Margarita Parra. Samuel Ceballos, Salvador Gil and Ana M.Costero, researchers of CIBER-BBN, Politecnic University of Valencia and University of Valencia were interested in detecting nitric oxide by different protocols and decided to study the Aggregation Induced Emission (AIE) phenomena as a possible transduction mechanism for detecting nitric oxide, compatible with aqueous media.

To sum up, a new probe capable of selectively detecting nitric oxide was prepared and evaluated. The probe is a tetraphenylethylene derivative and the transduction mechanism is really based on the Aggregation Induced Emission (AIE) phenomena. The click reaction catalyzed by NO modifies the steric volume of the TPE substituents inducing clear changes in the fluorescence emission. A limit of detection of 15 ppm has been determined and the linearity range appears between 20 and 80 ppm suggesting that the probe could be useful to control the use of iNO. Other gases such as NO2, CO2, CO and SO2 do not induce appreciable changes in the measure range. The probe works properly in MeOH:H2O media.

NMR spectra were registered at the Unit 26 of ICTS “NANBIOSIS”: NMR: Biomedical Applications II of ICBER-BBN at the Universitat of Valencia led by Ramón Martínez Máñez and Salvador Gil Grau.

Article of reference:

Silvia Rodríguez-Nuévalos, Margarita Parra. Samuel Ceballos, Salvador Gil, Ana M.Costero. A nitric oxide induced “click” reaction to trigger the aggregation induced emission (AIE) phenomena of a tetraphenyl ethylene derivative: A new fluorescent probe for NO. JOURNAL OF PHOTOCHEMISTRY AND PHOTOBIOLOGY A-CHEMISTRY. Vol: 388. 2020 https://doi.org/10.1016/j.jphotochem.2019.112132

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Tumor Immunology and Cancer Immunotherapy Course

The IV course on Tumor Immunology and Cancer Immunotherapy will start on 6th Feb, 2020.

On April 2 at 7:00 pm Iñaki Ochoa will teach about “Basic research in cancer immunotherapy. Use of microfluidics in the study of cancer immunotherapy“.

Ignacio Ochoa is a Professor of the Department of Human Anatomy and Histology of the University of Zaragoza and researcher of the
AMB – Applied Mechanics and Bioengineering group and NANBIOSIS U13 Tissue & Scaffold Characterization Unit from CIBER-BBN and I3A-Zaragoza University

Classes will be held on Thursday, from 4:00 p.m. to 8:00 p.m., in the CIBA Lorente de Nó Assembly Hall (with an exception that is detailed in the program) starting on 6th Feb, 2020.

It is an ongoing training course. Price: 173 €. Includes Online Access to the book “Tumor Immunology and Cancer Immunotherapy” by Amazing Books 2018

Program and registration: https://eventos.unizar.es/44697/programme/curso-de-inmunologia-tumoral-e-inmunoterapia-del-cancer.html

https://seom.org/otros-servicios/agenda/333-iv-curso-de-inmunologia-tumoral-e-inmunoterapia-del-cancer

Request pre-registration form Alberto Anel anel@unizar.es

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New nanocarrier for bio-imaging and drug-delivery applications

Researchers of CIBER-BBN and NANBIOSIS-ICTS (U6 Biomaterial Processing and Nanostructuring Unit at ICMAB-CSIC and U18 Nanotoxicology Unit at Hospital de la Santa Creu i Sant Pau have developed a new nanocarrier for bio-imaging and drug-delivery applications

The new nanovesicle formulation is based on the quatsome architecture – which stands out due to the high colloidal stability and homogeneity in size – and has now been shown to be suitable for in vivo dosing.

Quatsomes are new non-liposomal lipid-based nanovesicles that have been developed by Nanomol group in recent years, and have been shown to be highly homogeneous and stable in different media for years. This colloidal stability involves important advantages for the development of pharmaceutical formulations and for guaranteeing the final product quality. Quatsomes are a promising nanocarrier for bio-imaging and drug-delivery applications, suitable for the encapsulation of both hydrophilic and hydrophobic molecules, easily functionalized with elements that favor the directionality towards therapeutic targets.

To facilitate their use in in vivo applications, Nanomol group has now developed a new Quatsome formulation, composed of cholesterol and myristalkonium chloride (MKC), the C14 homolog of benzalkonium chloride (BAK), the latter being extensively used as antimicrobial preservative in many ophthalmic and parenteral formulations on the EU and USA market. These novel MKC-Quatsomes have been synthesized in different media that are suitable for parenteral administration, in which they showed to be stable for at least 18 months. Moreover, vesicles remained stable in human serum for at least 24 hours.

In collaboration with the Oncogenesis and Antitumour Drug group of the Biomedical Research Institute of the Hospital de la Santa Creu i Sant Pau, these MKC-Quatsomes were tested in live mice bearing xenografted colorectal tumors. After intravenous injection of fluorescently labelled MKC-Quatsomes, biodistribution assays showed nanovesicle accumulation in tumors, liver, spleen, and kidneys, but not in any other organ. Importantly, MKC-Quatsomes were well-tolerated at the administered doses, and no histological alterations or toxicity was found in any of these organs. These new results suggest the applicability of quatsomes in therapeutic approaches that require systemic delivery.

NANOMOL group, Coordinator of NANBIOSIS U6 at ICMAB-CSIC and the Oncogenesis and Antitumor Drug group, coordinator NANBIOSIS U18 at Biomedical Research Institute (Hospital de la Santa Creu i Sant Pau) are members of Biomedical Research Networking center in Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN) and have a wide expertise and recognized excellence in the synthesis, processing and study of molecular and polymeric materials and the study of their biomedical properties. NANOMOL is also a member of the technology transfer network TECNIO. ‘

Article of reference:

MKC-Quatsomes. A stable nanovesicle platform for bio-imaging and drug-delivery applications co-authored by Guillem Vargas-Nadal et al., Nanomedicine: Nanotechnology, Biology and Medicine, 24 (2020) 102136. https://doi.org/10.1016/j.nano.2019.102136

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BASIC COURSE FOR UROLOGIS: INTRACORPOREAL SUTURING

CCMIJU has organised the II Urological Laparoscopy Course: Suture Management and Intracorporeal Knotting which wil take place at JUMISC from 3 to 5 February under the Direction of Álvaro Serrano Pascual (Urology Service Specialist at the San Carlos Clinical Hospital, Madrid) and Francisco Miguel Sánchez Margallo (Deputy Scientific Director of NANBIOSIS)

It is a basic course of Laparoscopic Urology where the techniques of Laparoscopic Radical and Partial Nephrectomy will be carried out. The objective of this course is for specialists in Urology to improve their skills in suture management and intracorporeal knotting.

Programm and inscriptions here

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A step forward in the field of organic free radicals acting as chiral emitters

Researchers of NANBIOSIS U6. Biomaterial Processing and Nanostructuring Unit have just published the article titled “An enantiopure propeller ‐ like trityl ‐ brominated radical: Bringing together a high racemization barrier and an efficient circularly polarized luminescent magnetic emitter” in the scientific magazine Chemistry A European Journal.
The urgent need to cope with the more and more specific requirements in electronic devices is nowadays behind the search for new multifunctional materials. In this work, a step forward has been done in the field of organic free radicals acting as chiral emitters. The recently developed brominated trityl derivative, namely TTBrM radical, shows a satisfactory luminescent dissymmetry factor (|glum(592 nm)| ≈ 0.7 x 10-3) despite its pure organic nature. However, in contrast to its chlorinated homologues, no hints of racemization were observed up to 60 ° C for more than two hours, due to the higher steric hindrance imposed by the bulky Br atoms. Moreover, improved derivatives can be envisaged from this compound thanks to the wide possibilities that Br atoms at para-positions offer for further functionalization.

To see the article:

Jaume Veciana, Paula Mayorga-Burrezo, Vicente G. Jiménez, Davide Blasi, Teodor Parella, Imma Ratera, Araceli G. Campaña. An enantiopure propeller‐like trityl‐brominated radical: Bringing together a high racemization barrier and an efficient circularly polarized luminescent magnetic emitter. Chem. Eur. J. 10.1002/chem.202000098. 9 January 2020

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A step forward for the design of multifunctional protein nanomaterials for cancer therapies

Researchers of NANBIOSIS Unit 1 and NANBIOSIS Unit 18, led by Prof Antoni Villaverde have published the article at the prestigious scintific magazine titled Collaborative membrane activity and receptor-dependent tumor cell targeting for precise nanoparticle delivery in CXCR4+ colorectal cancer

The researchers have shown that the combination of cell-penetrating and tumor cell-targeting peptides dramatically enhances precise tumor accumulation of protein-only nanoparticles intended for selective drug delivery, in mouse models of human colorectal cancer. This fact is a step forward for the rational design of multifunctional protein nanomaterials for improved cancer therapies.

Protein production has been partially performed by the ICTS NANBIOSIS U1, Protein Production Platform and the nanoparticle size analysis by the U6 of NANBIOSIS Biomaterial Processing and Nanostructuring Unit. Biodistribution studies were performed by the U18 of the ICTS NANBIOSIS, Nanotoxicology Unit.

Article of reference:

Rita Sala, LauraSánchez-García, Naroa Serna, María Virtudes Céspedes, Isolda Casanova, Mònica Roldán, Alejandro Sánchez Chardig, Ugutz Unzueta, Esther Vázquez, Ramón Mangues, Antonio Villaverde. Collaborative membrane activity and receptor-dependent tumor cell targeting for precise nanoparticle delivery in CXCR4+ colorectal cancer. Acta Biomaterialia, 99, Pages 426-432. 2019,

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Pilar Marco honored by the Spanish National Research Council (CSIC)

Maria Pilar Marco Colás has been honored by the Spanish National Research Council (CSIC) in appreciation for having complited 25 years of work at the CSIC, an intense period of 25 years at the service of Science, 11 of them as Scientific Director of Custom Antibody Service (CAbS), unit 2 of NANBIOSIS since its inclusion in the national ICTS map.

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Why the poor biodistribution so far reached by tumor-targeted medicines?

Cell-selective targeting is expected to enhance effectiveness and minimize side effects of cytotoxic agents. Functionalization of drugs or drug nanoconjugates with specific cell ligands allows receptor-mediated selective cell delivery. However, it is unclear whether the incorporation of an efficient ligand into a drug vehicle is sufficient to ensure proper biodistribution upon systemic administration, and also at which extent biophysical properties of the vehicle may contribute to the accumulation in target tissues during active targeting. To approach this issue, structural robustness of self-assembling, protein-only nanoparticles targeted to the tumoral marker CXCR4 is compromised by reducing the number of histidine residues (from six to five) in a histidine-based architectonic tag. Thus, the structure of the resulting nanoparticles, but not of building blocks, is weakened. Upon intravenous injection in animal models of human CXCR4+ colorectal cancer, the administered material loses the ability to accumulate in tumor tissue, where it is only transiently found. It instead deposits in kidney and liver. Therefore, precise cell-targeted delivery requires not only the incorporation of a proper ligand that promotes receptor-mediated internalization, but also, unexpectedly, its maintenance of a stable multimeric nanostructure that ensures high ligand exposure and long residence time in tumor tissue.

The concept presented by the authors of the present research might represent a convincing explanation of the poor biodistribution so far reached by tumor-targeted medicines, including antibody-drug conjugates. In addition to this, they offer a potential developmental roadmap for the improvement of these drugs, of high intrinsic therapeutic potential, to reach satisfactory efficiencies in the clinical context.

Hèctor López-Laguna, Rita Sala, Julieta M. Sánchez, Patricia Álamo, Ugutz Unzueta, Alejandro Sánchez-Chardi, Naroa Serna, Laura Sánchez-García, Eric Voltà-Durán, Ramón Mangues, Antonio Villaverde and Esther Vázquez. Nanostructure Empowers Active Tumor Targeting in Ligand-Based Molecular Delivery. Part. Part. Syst. Charact. 2019.

DOI: 10.1002/ppsc.201900304

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Artificial inclusion bodies for controlled drug release

Researchers from NANBIOSIS-CIBER-BBN have developed a new type of protein biomaterial that allows a continuous release over time of therapeutic proteins when administered subcutaneously in laboratory animals.

These results are the result of the stable scientific collaboration between the researchers of NANBIOSIS Units 1 Protein Production Platform (PPP)and 18 Nanotoxicology Unit, led by Toni Villaverde and Ramón Mangues at the Institute of Biotechnology and Biomedicine of the Autonomous University of Barcelona (IBB-UAB) and the Institut About the Hospital de Sant Pau and has had the participation of the Institute of Biological and Technological Research of the National University of Córdoba-CONICET, in Argentina

“These structures, of a few micrometers in diameter, contain functional proteins that are released in a manner similar to the release of human hormones in the endocrine system,” says Antonio Villaverde. Ramón Mangues explains that “the new biomaterial mimics a common bacterial product in biotechnological processes called ‘inclusion bodies’, of pharmacological interest, which in this artificial version offers a wide range of therapeutic possibilities in the field of oncology and in any other field clinic that requires sustained release over time.” Researchers have used common enzymes in biotechnology as a model and a nanostructured bacterial toxin that targets metastatic cells of human colorectal cancer, which has been tested in animal models. “In this way we have managed to generate both immobilized catalysts and a new long-acting anti-tumor drug,” said the researchers responsible for the research.

The developed artificial protein granules, which had previously been proposed as ‘nanopills’ (tablets of therapeutic material on a nanoscopic scale), mimic bacterial inclusion bodies and offer enormous clinical potential in the field of vaccinology and as release systems Drug controlled.

“We have seen that natural inclusion bodies, administered as medicines, can generate unwanted immune responses due to the inevitable contamination with bacterial materials,” the researchers comment. However, in the new work, the development of artificial inclusion bodies with secretion capacity “avoids many of the regulatory problems associated with the potential development of bacterial nanopills, and offers a cross platform for obtaining functional components in cosmetics and in clinic” they add.

This work points to artificial inclusion bodies as a new exploitable category of biomaterials for biotechnological applications with a more simple manufacturing and clinical applications.

Reference article:
Julieta M. Sánchez, Hèctor López ‐ Laguna, Patricia Álamo, Naroa Serna, Alejandro Sánchez ‐ Chardi, Verónica Nolan, Olivia Cano ‐ Garrido, Isolda Casanova, Ugutz Unzueta, Esther Vazquez, Ramon Mangues, Antonio Villaverde Artificial Inclusion Bodies for Clinical Development

https: //doi.org/10.1002/advs.201902420

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