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News U26

News U26

Three Nanbiosis units work in the development of new sensors for the better detection of the fungus P. jirovecii, responsible for Pneumocystis pneumonia

Researchers from the CIBER-BBN have succeeded in developing detection systems for Pneumocystis jirovecii, an atypical fungus responsible for very serious pneumonia in immunosuppressed patients. These results, published in the journal Nanomaterials, are the result of collaboration between the CIBER-BBN groups led by Laura Lechuga, Ramon Eritja and Ramón Martínez Máñez, and the CIBERESP group led by Enrique J. Calderón.

The researchers acknowledge the paricipation of three NANBIOSIS units of CIBER-BBN:

The detection of the fungus in patients, who may be asymptomatic carriers until they develop pneumonia, is currently carried out using the PCR technique, requiring several hours, adequate facilities and qualified personnel to detect it. Now, the application of Nanotechnology has allowed the development of more sensitive and efficient biosensors to detect specific sequences corresponding to pathogens responsible for infectious diseases in a shorter time and without the need for large infrastructures.

In this case, a specific sequence corresponding to the gene belonging to the ribosomal subunit (mtLSU rRNA) of the P. jirovecii fungus has been detected using hairpin-shaped capture probes. These specific probes, as pointed out by Dr. Aviñó, a researcher at CIBER-BBN at the IQAC-CSIC, “are more efficient and are capable of recognizing a specific genomic sequence of the fungus and forming very stable triplex structures that can be detected on different platforms. biosensor “.

Laura Lechuga’s team at ICN2, through the use of an optical biosensor based on SPR technology, has detected in real time and without the use of markers, P. jirovecii in bronchoalveolar lavages and nasopharyngeal aspirates with a detection limit of nM level and in just a few minutes.

Likewise, the group led by Ramón Martínez-Máñez, scientific director of CIBER-BBN and principal investigator of the IQMA-IDM group at the Universitat Politècnica de València, has used the strategy of molecular gates composed of an anodic albumin matrix to develop a sensor capable of to efficiently detect real P. jirovecii samples without previous amplification steps in as little as one hour.

“These advances in the diagnosis of PCP have great potential for the development of highly sensitive point-of-care devices using direct patient samples and applicable in a wide variety of settings,” says the CIBERESP group leader. Enrique J. Calderón from the Virgen del Rocío University Hospital in Seville.

The researchers also emphasize that these techniques are very selective and can discriminate patients with other respiratory diseases derived from other microorganisms, thus allowing a more reliable diagnosis of infectious diseases.

Articles of reference:

Calvo-Lozano, O., Aviñó, A., Friaza, V., Medina-Escuela, A., S Huertas, C., Calderón, E. J., Eritja, E., Lechuga, L. M. (2020). Fast and accurate pneumocystis pneumonia diagnosis in human samples using a label-free plasmonic biosensor. Nanomaterials, 10(6), 1246. https://doi.org/10.3390/nano10061246

Pla, L., Santiago-Felipe, S., Aviñó, A., Eritja, R., Ruiz-Gaitán, A., Pemán, J., Friaza, V., Calderón, E.J. Martínez-Máñez, R., Aznar E. (2020). Triplex hybridization-based nanosystem for the rapid screening of Pneumocystis pneumonia in clinical samples. Journal of Fungi, 6(4), 292. https://doi.org/10.3390/jof6040292

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The Nanomedicine Revolution

Yesterday, November, 25 took place, within the the program of the Ateneo of the EINA (School of Engineering and Architecture of Aragón), the online conference on “The Revolution of Nanomedicine” by Ramón Martínez Máñez.

The Conference chair, Jesús Martínez de la Fuente, Principal Investigator of the BIONANOSURF group of CIBER-BBN and the Institute of Nanoscience and Materials of Aragón, introduced the guest, Ramón Martínez Máñez, Scientific Director of CIBER-BBN, highlighting “his creativity in the use of his systems and how he combines them with different diagnostic release systems, combining organic chemistry, surface chemistry, applications in biotechnology and giving way to translation and transfer, his works are very unique

Ramón Martínez Máñez, Scientific Director NANBIOSIS unit 26 NMR: Biomedical Applications II, gave a very instructive talke about what is nanotechnology and how nanotechnology revolution has reached the medicine, with current examples of the application of nanomedicines, as well as in the medicine of the future.

After it, a very interesting debate took place in which different issues were discussed, especially in relation to nanomedicine applied to therapy, such as the barriers to generalize the use of nanoparticles in therapy, the current state of implantation of nanoformulated drugs in the market and the advancement of the use of some nanoparticles as polymers or liposomes compared to inorganic nanoparticles, the degree of development of nanoparticles under GLP certification or why cancer is the main target of nanomedicine with a great difference over other pathologies. The audience asked questions that led to the discussion of some more controversial points such as whether it is true that “Big Pharma” does not like nanoparticles, why there is a regulatory vacuum regarding their use and how to solve these problems.

Regarding the diagnosis applications, Ramón Martínez commented that “nanotechnology already has its way open, both in the development of nanoparticles and systems to amplify the signal, based on nanophotonics, resonant rings or other technologies at the nanometric level. The pandemic has highlighted the importance of having rapid detection systems for bio parameters, pathogens, bacteria … We have a lot of knowledge acquired in recent years in these systems and they are currently being developed in a more or less short time, we are truly close to revolutionizing the field of detection“.

Finally, in realtion with the nanomedicine of the future, the questions raised in the debate revolved mainly around nanobots and their state of development or the problems that are emerging in it or the possibility of uniting nanomedicine with artificial intelligence and possible applications.

The Ateneo is an activity of the EINA in collaboration with the Aragón Engineering Research Institute and SAMCA Chair of Technological Development of Aragon, both directed by Pablo Laguna, Scientific Director of Nanbiosis U27 High Performance Computing. Pablo Laguna closed the event thanking Ramón Martínez Máñez and Jesús Martínez de la Fuente for their participation and highlighting the high number of attendees at the conference.

The conference can be followed in Spanish in EINA youtoube channel: https://www.youtube.com/watch?v=Y_Fh1O1VuNU

Anouncing this Conference in the Ateneo EINA, Ramón Martínez Máñez was yesterday interviewed by Aragon Radio. In this case, the interview had the focuss in the “Nanomedicine against COVID” . The podcast can be listen in Spanish here: https://www.cartv.es/aragonradio/podcast/emision/nanomedicina-frente-a-la-covid

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How to delay vision loss in hereditary retinal dystrophies? Looking for the most effective and economical pharmacological nanotherapy

Researchers from the CIBER-BBN and NANBIOSIS are participating in a new project that aims to achieve the most effective, specific and economical pharmacological nanotherapy that allows delaying the death of retinal cells and subsequent loss of vision in hereditary retinal dystrophy. retinitis pigmentosa, regardless of the genetic defect causing the disease.

In this project, coordinated by the researcher Regina Rodrigo, the ONCE and the Prince Felipe Research Center (CIPF) of Valencia collaborate, together with researchers from the CIBER of Rare Diseases (CIBERER) and the Manises Hospital in Valencia. On behalf of the CIBER-BBN, the scientific director, Ramón Martínez Máñez, together with Elena Aznar from the IDM-UPV group of the Polytechnic University of València, José Luís Pedraz, Gustavo Puras and Idoia Gallego, from the group of the University of the Basque Country and Nanbiosis.

The NANBIOSIS participation in the project will be through the U10 Drug Formulation unit (from @CIBERBBN and @upvehu), led by NanoBioCell Group and Prof. José Luis Pedraz and U26 NMR: Biomedical Applications II , led by IDM-UPV-UV Group, led by Prof. Ramón Martínez Máñez. Elena Aznar, researcher of CIBER-BBN at IDM-UPV-UV explained “We use the unit to characterize the nanoparticles. Through a solid phase NMR confirms that the molecular gate has been correctly attached to the surface of the nanoparticles“.

Retinitis pigmentosa is a group of inherited retinal dystrophies characterized by progressive and irreversible loss of vision. Although it is considered a rare disease, it is the leading genetic cause of blindness in developed countries. So far there is no effective treatment, although there are various therapeutic approaches such as gene therapy, cell therapy, pharmacological therapy, optogenetics or electronic implants.

During the progression of the disease, an important inflammatory component has been observed that may contribute to its pathogenesis. In this sense, different anti-inflammatory strategies have been evaluated. The research group has successfully tested one of these strategies in preclinical models of retinitis pigmentosa. However, the implementation of this therapeutic strategy with nanocarriers as controlled release delivery systems would improve the mode of action of the administered drug, avoiding its degradation, increasing its half-life, stability or its availability in the retina. In this project, two types of nanocarriers will be used and their effect on the degenerative process in a murine model of retinitis pigmentosa will be evaluated.

  • PICTURE: Hematoxylin and eosin image showing that intravitreal blockade of the cytokine TNFα with Adalimumab-type monoclonal antibodies (ADA) reduces retinal degeneration, preventing the death of photoreceptors (RF) in the murine model of retinitis pigmentosa, rd10 mouse.
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New test trials to diagnose Covid 19: Ramon Martinez, Scientific Director of CIBER-BBN is interviewed by Spanish Television

Ramón Martinez, Scientific Director of CIBER-BBN and NANBIOSIS unit 26 NMR: Biomedical Applications II is interviewed by Spanish Television about the research he is coordinating at the Polytechnic University of Valencia to develop new tests as an alternative to PCR.

Dr. Elena Aznar CIBER researcher at IQMA-IDM-UPV group explains how work these test that allow to diagnose quickly, easily, reliably and cheaply if a person is or has been infected by the SARS-COV-2 virus. Ramón Martínez Máñez, leader of the project, reports on the point where the investigation is, as well as the difference of these tests with PCR or antigen tests. These tests implement a technology of the research group that has already been used for other pathogens and that they try to adapt to the COVID virus. “My impression – explains Dr. Martínez – is that the time will come when these tests can be sold in pharmacies and can be used by the users themselves. At the moment we have to see if they work in patient samples and then adapt it so that be a marketable kit by an interested company

The interview can be whatched here:

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COVID-19 detection system: a fast, cheap and easy to use alternative to PCR.

PCR (acronym in English for “Polymeric Chain Reaction”), is a type of diagnostic test for the detection of infectious diseases. The PCR diagnosis of COVID-19 used since the outbreak of the pandemic offers a high level of specificity and sensitivity but presents a certain degree of complexity, requiring specialized personnel and is expensive.

Researchers from Polytechnic University of Valencia (UPV), the Foundation for the Promotion of Health and Biomedical Research of the Valencian Community (FISABIO), the La Fe Health Research Institute (IIS La Fe) and the consortium Centro de Investigación Biomédica en Red de Bioengineering, Biomateriales y Nanomedicina (CIBER-BBN) has been working, during the pandemic. Within the framework of the Diacovid project, different tests have been carried out with a first prototype of a rapid point-of-care (POC) test, based on nanosystems with molecular gates, that would detect quickly, reliably and easily, SARS-CoV-2.

Ramón Martínez Máñez, Scientific Director of Nanbiosis U26 NMR: Biomedical Applications II explains the advantages of POC techniques as their ability to diagnose in sites with limited infrastructure, without specially qualified staf and without the requirement to transport the sample to a centralized facility. In addition, POC technologies are global detection tools for surveillance against possible new outbreaks in the future. Its use would allow the rapid implementation of containment measures, reduction of therapeutic response times, in situ detection and the use of a low sample volume.

Further information and News in UPV TV

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II Conference on Nanotoxicity. “Dosis sola facit venenum”

NANBIOSIS has participated in the organization of the on-line Conference on Nanotoxicity in collaboration with, CIBER-BBNNanomed Spain and Materplat, to debate about the efect of nanotoxicity of nanoparticles and nanotechnologies in health.

The session has been started by Ramon Martinez Mañez, Scientific Director of CIBER-BBN and NANBIOSIS U26 NMR: Biomedical Applications II.

Isabel Rodriguez (GAIKER Technlogy Center) has taking about tools for risk management of nanomatials differentiating between tools and strategies and explaining their experience in studies carried out.

Luis Rojo del Olmo investigador del Grupo de Biomateriales del Instituto de Ciencia y Tecnología de Polímeros del CSIC y del CIBER-BBN) has spoken about the physical-chemical characterization of micro and nanoplastics, explaining biodegradation and bioelimination techniques and their relationship with nanotoxicity.

Ariel Ramírez from the Nanotoxicology Unit of the Aragon Health Research Institute (IIS Aragón) has spoken about preclinical characterization of micro and nanoplastics.

Finally, Ciro Luis Salcines from the University of Cantabria spoke about the practical application of NanoPrevention and Nanotoxicology.

The talks have been followed by a round table of great scientific interest. Ernesto Caballero Garrido, from the Spanish Agency for Medicines and Health Products (AEMPS) has shown that sometimes the evaluation of “nano” goes through the evaluation of “macro”, as there is a lack of specific regulation, in this case the two additional aspects to be taken into account to determine nanotoxicity are accumulation and elimination.

Ramón Martínez Mañez closed the session thanking the organization of the Conference and inviting to continue with these Annual Conference on Nanotoxicity, a topic of great interest to the CIBER-BBN

The Conference was moderated by Teresa Sanchis, executive coordinator of Nanomed.

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Seminar on Molecular probes and gated materials in biomedical applications by Ramón Martínez, now in youtube

Last June 8, 2020,  Ramón Martínez Máñez, Scientific Director of CIBER-BBN and NANBIOSIS U26, gave an on line seminar, hosted by Jaume Veciana and Anna Roig will from ICMAB-CSIC on Molecular probes and gated materials in biomedical applications and communication between nanoparticles.

If you missed the seminar, you can see it now on YouTube:

More information at the ICMAB website.

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NANBIOSIS researchers featured in the 15th Edition of Spanish Researchers Ranking

The 15th edition of the Webometrics Ranking of World Universities has been published, ranking researchers in Spain as well as Spaniards doing research abroad. A total of 11 Directors of NANBIOSIS units appear on the most recent list, featured on the top 2000. The list is ordered by the h-index, a metric that calculates research impact based on a correlation of papers published and number of citations, and then by number of citations. The result is a list of whose’s publications have had more impact online.

NANBIOSIS researchers featured are Fernando Albericio (#207), scientific director of U3 Synthesis of Peptides Unit, Ramón Martínez Máñez (#342) U26 NMR: Biomedical Applications II, Jaume Veciana (#459) U6 Biomaterial Processing and Nanostructuring Unit, José Luis Pedraz (#906) U10 Drug Formulation unit, Jesús Santamaría (#912) U9 Synthesis of Nanoparticles Unit, Ramón Eritja (#1022) U29 Oligonucleotide Synthesis Platform (OSP), Pablo Laguna (#1153) U27 High Performance Computing, Antoni Villaverde (#1249) U1 Protein Production Platform (PPP), Laura Lechuga (#1511) U4 Biodeposition and Biodetection Unit M.Pilar Marco (#1517), U2 Custom Antibody Service (CAbS), and Josep Samitier (#1836) U7 Nanotechnology Unit.

This list reflects on the impact online publication can have as a tool to share knowledge. 

For further information: here

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Peptide‐Capped Mesoporous Nanoparticles: Toward a more Efficient Internalization of Alendronate.

Osteoporosis is an illness which appears when the osteoblast/osteoclast activities are unbalanced taking place bone resorption (caused by osteoclasts) in higher extension than bone formation (induced by osteoblasts). Alendronate is one of the most used drugs for osteoporosis treatment despite its scarce bioavailability. In an attempt to improve it, gated mesoporous silica nanoparticles, for the controlled release of alendronate, have been synthesized and characterized. These hybrid nanoparticles include labelled alendronate inside the porous, those porous are capped with a peptide designed to be selectively cleaved by cathepsin K enzyme (overexpressed in osteoclasts).

Two CIBER-BBN units of the ICTS NANBIOSIS were implied in the research: the peptide was prepared by U3 Synthesis of Peptides Unit and substances were characterized at U26 NMR: Biomedical Applications II Unit at University of Valencia.

The nanoparticles were internalized by RAW 264.7 macrophages (which could differentiate in osteoclasts) and were able to release its entrapped cargo in the presence of cathepsin K added in the macrophage lysates. From the set with aminopropyl functionalized silica, loaded with nitrobenzofurazan labelled alendronate and capped with the same peptide, 4.2% of the total alendronate amount in contact with the cells is liberated inside them and could produce its therapeutic effect.

Article of reference:

Elena Añón, Ana M. Costero, Pedro Amorós, Jamal El Haskouri, Ramón Martínez‐Mánez, Margarita Parra, Salvador Gil, Pablo Gaviña, M. Carmen Terencio, María Alfonso. Peptide-Capped. Mesoporous Nanoparticles: Toward a more Efficient Internalization of  Alendronate. Chemistry Europe, March 2020

https://doi.org/10.1002/slct.202000417

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New therapy for triple negative breast cancer is successfully tested in preclinical animals

Researchers CIBER-BBN and NANBIOSIS Unit 26, the Príncipe Felipe Research Center (CIPF), the Universitat Politècnica de València (UPV) and the Institut de Recerca Biomèdica (IRB) of Barcelona manage to inhibit tumor growth, reduce metastasis and decrease the toxicity of the antitumor drug Navitoclax in preclinical animal models of triple negative breast cancer (TNBC).

These types of TNBC tumors do not express any of the three receptors involved in most breast cancers (estrogen, progesterone, and HER2), so the most common treatments such as hormone therapy are not viable in these patients.

This new study, led by Mar Orzáez, principal investigator of the CIPF Peptides and Proteins Laboratory and Ramón Martínez Máñez, scientific director of CIBER-BBN, NANBIOSIS Unit 26, member of the CIPF-UPV Joint Unit in Mechanisms of disease and Nanomedicine and researcher at the Interuniversity Institute of Research on Molecular Recognition and Technological Development (IDM) at UPV, shows that a combined treatment of a senescence inducer and a senolytic nanoparticle, selectively removes senescent cells, delays tumor growth and reduces metastasis in a mouse model of aggressive breast cancer.

Until now, the application of senescence inducers represents a successful treatment strategy in patients with breast cancer, although the accumulation of senescent cells in the body can sometimes promote tumor recurrence.

Cell senescence or aging takes place in both physiological and pathological situations. When a cell goes into senescence, it stops dividing and releases substances that cause inflammation.

When an uncontrolled accumulation of these senescent cells occurs, the excess of inflammatory factors can end up damaging healthy cells, thereby contributing to aging, the appearance of pathologies such as diabetes, neurodegenerative diseases or promoting the development of tumors and promoting metastasis.

With this new approach, after the induction of senescence, the cells are eliminated by treatment with a senolytic nanoparticle, and a new therapeutic opportunity opens up to improve the results in patients with breast cancer and a new combined treatment is proposed that may be relevant to other senescence-inducing chemotherapeutic drugs.

The results, published in the Journal of Controlled Release (JCR), offer new therapeutic approaches to advance in later phases and clinical trials and allow different tumor types to be addressed.

Orzáez and Máñez have pointed out that “the induction of senescence in tumors represents an advance in the treatment of cancer, which may be even greater in combination with this type of senolytic treatments that eliminate senescent cells and help reduce metastasis.”

Manuel Serrano from the Institut de Recerca Biomèdica (IRB) in Barcelona has also collaborated in the study.

Article of reference:

Irene Galiana, Beatriz Lozano-Torres, Mónica Sancho, María Alfonso, Andrea Bernardos, Viviana Bisbal, Manuel Serrano, Ramón Martínez-Máñez, Mar Orzáez, Preclinical antitumor efficacy of senescence-inducing chemotherapy combined with a nanoSenolytic, Journal of Controlled Release, Volume 323 https://doi.org/10.1016/j.jconrel.2020.04.045

Sourse of information: CIBER-BBN

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