2021 - Nanbiosis

New results evidence new biomarkers for early diagnosis of P. aeruginosa infections

Pseudomonas aeruginosa is a common multidrug-resistant pathogen that causes acute and chronic infections. However, P. aeruginosa, as many other bacterial species, has developed resistance to antibiotics being difficult to treat. For this reason diagnostic methods allowing detection at early stages of the infection are required and, therefore, efficient biomarkers of infection are very helpful. These fast diagnosis will help on the subsequent therapeutic treatment.

The Nb4D group of CIBER-BBN and IQAC-CSIC (led by M.-Pilar Marco) has recently conducted a research to develop a highly sensitive, specific and reliable immunochemical assay to detect pyocyanin (PYO), one of the most important virulence factors of Pseudomonas aeruginosa.

The assay uses a high-affinity monoclonal antibody produced by the unit 2 of the ICTS NANBIOSIS Custom Antibody Service (CAbS) (Dr. Núria Pascual).

The microplate-based ELISA developed is able to achieve a limit of detection (LoD) of 0.07 nM, which is much lower than the concentrations reported to be found in clinical samples (130 µM in sputa and 2.8 µM in ear secretions). The ELISA has allowed the investigation of the release kinetics of PYO and 1-OHphz (the main metabolite of PYO) of clinical isolates from P. aeruginosa-infected patients. Significant differences have been found between clinical isolates obtained from patients suffering an acute or a chronic infection (~6,000 nM vs. ~8 nM of PYO content, respectively).

The results found point to a real potential of PYO as a biomarker of P. aeruginosa infection and the possibility to use such virulence factor also as a biomarker for patient stratification and for an effective management of these kinds of infections.

Article of referece:

Rodriguez-Urretavizcaya, B., Pascual, N., Pastells, C., Martin-Gomez, M.-T., Vilaplana, Ll.*, Marco. M.-P. (2021). “Diagnosis and Stratification of Pseudomonas aeruginosa Infected Patients by Immunochemical Quantitative Determination of Pyocyanin From Clinical Bacterial Isolates.” Frontiers in Cellular and Infection Microbiology 11(1215). https://doi.org/10.1016/j.jmbbm.2021.104793

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Two great scientists and excellent people pioneers on Nucleic Acids Chemistry

Nucleic Acid Chemistry is an interdisciplinary discipline that combines organic chemistry, biochemistry, pharmacology, materials chemistry and biophysics. It started soon after the Watson–Crick model of DNA with the synthesis of the first dinucleotide, published in 1955. However, in the last decade, this field has blossomed, with the demonstration that Nucleic Acid Chemistry can provide innovative solutions to health problems such as vaccination, pathogen detection, and the treatment of metabolic or genetic diseases as well as providing important tools for the interrogation of cellular mechanisms.

Profesor Ramon Eritja, Scientific director of the Oligonucleotides Synthesis Platform U29 from ICTS NANBIOSIS will chair next January 13 a webinar on Frontiers in Nucleic Acid Chemistry, organized by the Journal Molecules in which some examples of the recent developments in Nucleic Acid Chemistry will be explained.

This webinar is dedicated to the memory of Prof. Enrique Pedroso one of pioneering researchers and leading Spanish scientist in Oligonucleotide and Peptide Synthesis who passed away in September of 2020. His contributions on the synthesis of modified oligonucleotides and especially oligonucleotide conjugates and cyclic oligonucleotides have opened new avenues in the search for novel applications of oligonucleotides. In addition, Enrique was deeply involved in the research and promotion of nucleic acid chemistry, as an active member of the IRT Society as well as organizing the Spanish Nucleosides Nucleotides and Nucleic Acids meetings (RANN).

During the preparation of the webinar we received the sad news of the decease of Prof. Ned Seeman from New York University who pioneered the field of DNA nanobiotechnology demonstrating that DNA is an excellent tool for the assembly of complex two and three-dimensional DNA lattices with important applications in several fields.

We remained sad for the loss of these great scientists and excellent persons.

Program and free registry for the webinar here

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The suitability of flexible graphene depth neuralprobes for in vivo electrophysiology research

A study published in “Nature Nanotechnology” shows that flexible brain probes made of graphene micro-transistors can be used to record pathological brain signals associated with epilepsy with excellent fidelity and high spatial resolution.

This research was led by the Catalan Institute of Nanoscience and Nanotechnology (ICN2), the Institute of Microelectronics of Barcelona (IMB-CNM-CSIC) and the University College London Queen Square Institute of Neurology (UK).

Barcelona, Wednesday 22 December 2021. The ability to record and map the full range of brain signals using electrophysiological probes will greatly advance our understanding of brain diseases and aid the clinical management of patients with diverse neurological disorders. However, current technologies are limited in their ability to accurately obtain with high spatial fidelity ultraslow brain signals. In a paper published today in Nature Nanotechnology, an international team of researchers report a flexible neural probe made of graphene-based field-effect transistors capable of recording the full spectrum of brain signals, including infraslow; and demonstrate the ability of these devices to detect with high fidelity electrographic signatures of the epileptic brain.

Epilepsy is the most common serious brain disorder worldwide, with up to 30% of people unable to control their seizures using traditional anti-epileptic drugs. For drug-refractory patients, epilepsy surgery may be a viable option. Surgical removal of the area of the brain where the seizures first start can result in seizure freedom; however, the success of surgery relies on accurately identifying the seizure onset zone (SOZ). Epileptic signals span over a wide range of frequencies –much larger than the band monitored in conventional EEG. Electrographic biomarkers of a SOZ include very fast oscillations as well as infraslow activity and direct-current (DC) shifts. The latter, in particular, can provide very relevant information associated with seizure onset but are seldom used due to the poor performance of current probes to record these types of slow brain signals. Application of this technology will allow researchers to investigate the role infraslow oscillations play in promoting susceptibility windows for the transition to seizure, as well as improving detection of clinically relevant electrophysiological biomarkers associated with epilepsy.

The graphene depth neural probe (gDNP) developed by the authors of this research consists of a millimetre-long linear array of micro-transistors imbedded in a micrometre-thin polymeric flexible substrate. The flexible gDNP devices were chronically implanted in small animal models of seizures and epilepsy. The implanted devices provided outstanding spatial resolution and very rich wide bandwidth recording of epileptic brain signals over weeks. In addition, extensive chronic biocompatibility tests confirmed no significant tissue damage and neuro-inflammation, attributed to the biocompatibility of the used materials, including graphene, and the flexible nature of the gDNP device.

Future clinical translation of this technology offers the possibility to identify and confine much more precisely the zones of the brain responsible for seizure onset before surgery, leading to less extensive resections and better outcomes. Ultimately, this technology can also be applied to improve our understanding of other neurological diseases associated with ultraslow brain signals, such as traumatic brain injury, stroke and migraine.

This study was led by ICREA Prof. Jose A Garrido, head of the ICN2 Advanced Electronic Materials and Devices Group, Dr Anton Guimerà-Brunet, from the Institute of Microelectronics of Barcelona (IMB-CNM-CSIC) & CIBER-BBN, and Dr Rob Wykes, from the University College London Queen Square Institute of Neurology (UK) & the Nanomedicine Lab of the University of Manchester (UK). First author of the paper is Dr Andrea Bonaccini Calia, a former member of Prof. Garrido’s group. This study was conducted in the frame of the EU project Graphene Flagship. It benefited from multidisciplinary collaborations and received valuable contributions from researchers at the Nanomedicine Lab of the University of Manchester (UK), the Universitat Autònoma de Barcelona (Spain), the CIBER-BBN with the participation of its ICTS NANBIOSIS and g.tec medical engineering GmbH (Austria).

NANBIOSIS U8. Micro – Nano Technology Unit has been used for the deposit of thin layers (Polyimide) for the manufacture of flexible devices (U8-S05) and for the growth and transfer of graphene (U8-S02) in flexible device disks.

Related animation

Reference article:

Andrea Bonaccini Calia, Eduard Masvidal-Codina, Trevor M. Smith, Nathan Schäfer, Daman Rathore, Elisa Rodríguez-Lucas, Xavi Illa, Jose M. De la Cruz, Elena Del Corro, Elisabet Prats-Alfonso, Damià Viana, Jessica Bousquet, Clement Hébert, Javier Martínez-Aguilar, Justin R. Sperling, Matthew Drummond, Arnab Halder, Abbie Dodd, Katharine Barr, Sinead Savage, Jordina Fornell, Jordi Sort, Christoph Guger, Rosa Villa, Kostas Kostarelos, Rob Wykes, Anton Guimerà-Brunet, and Jose A. Garrido, Full bandwidth electrophysiology of seizures and epileptiform activity enabled by flexible graphene micro-transistor depth neural probes. Nature Nanotechnology, 2021. DOI: https://dx.doi.org/10.1038/s41565-021-01041-9

For more information:

Institut Català de Nanociència i Nanotecnologia (ICN2)
Marketing and Communication Department
Àlex Argemí, Head of Marketing and Communication
alex.argemi@icn2.cat; +34 635 861 543

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1,800,000 euro for the improvement of NANBIOSIS laboratories

The final decision on the call for funding of Singular Scientific and Technical Infrastructures (ICTS) within the framework of the Recovery, Transformation and Resilience Plan in 2021 for has been published. These grants are intended to facilitate the execution of the Strategic Plans of the ICTSs included in the current National Map of ICTSs, through the execution of the investments provided for in their investment plans and declared of high priority by the Advisory Committee for Singular Infrastructures (CAIS).

Two applications were submitted to this call by NANBIOSIS: one by the CIBER node named “Towards a new generation of Infrastructure for the design, production and preclinical characterization of nanomedicines, biomaterials and biomedical systems in the units of the CIBER node of NANBIOSIS ” for the amount of € 2,522,128.02 of which € 1,785,706.36 have been granted, and another for the BIONAND node entitled “Update and improvement of the equipment of the BIONAND node of the NANBIOSIS distributed ICTS ”, for the amount of € 339,633.59, of which € 29,000 have been awarded.

These grants will allow the acquisition and improvement of the equipment and laboratories for the preclinical production and characterization of biomaterial nanomedicines and NANBIOSIS biomedical systems.

This call from the Ministry of Science and Innovation is funded with 37 million euros by the Recovery and Resilience Mechanism of the European Union. This is the first grant of aid for all ICTS in the last decade that is approved with funds from the General State Budget that finances 100% of the eligible costs and will allow the development and improvement of critical facilities for science and Spanish innovation. The Ministry of Science and Innovation has announced that in 2022 another call for 37 million euros will be published to finance actions of the new strategic plans of the ICTS 2021-2024.

The reinforcement of NANBIOSIS research capacities through these projects will result in a qualification of the research tissue at the national level necessary for the development of the next generation of advanced therapy drugs and diagnostic innovation linked to precision medicine and ensure the production of essential drugs.

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The Medicine of the Future needs the Nanomedicine Revolution. This is why

The medicine of the future is an increasingly tackled topic. In the context of global concern for the sustainability of the health system (chronic diseases, new disorders, aging population and financing problems), nanomedicine could promote more affordable and personalized health care and improve the quality of life of the patients.

Between innovative techniques already implemented and concepts that evoke science fiction (nanobots, fluorescent particles working as spies, tiny Trojan horses introduced into our body …), nanomedicine generates great expectations.

Nanomedicine, what is it exactly?

Nanomedicine is the application of nanotechnology to medicine, that is, the use of nanotechnologic systems for the prevention, diagnosis or treatment of diseases, due to the particular properties that materials present on a nanometric scale. (Yes, although it seems strange, the same material has totally different attributes and behaviours when “nano” amounts of it are manipulated, what is very important in medicine, since many of the processes of the human body take place on a nanometric scale).

The current state, thanks to the previous effort.

When in 1959 Richard Feynmand, (Nobel Prize in Physics in 1965), gave his speech “There is a lot of space down there”, he opened the door to research at the nano scale: from 1nm to 100nm, this is one-millionth of a millimeter (10^-9 meters); we are talking about the range of sizes resulting from dividing the diameter of a hair between 1,000 and 10,000, (or what a nail grows in a second).

Since the entry into the market of the first nanomedicine in 1995 (Doxil®, a drug encapsulated in liposomes for the treatment of cancer), nanoparticles or nanostructures have been developed for the controlled release of drugs in cancer and other pathologies, nanodevices have been created for disease diagnosis or nanomaterials have been designed for applications in regenerative medicine, and even messenger RNA vaccines for Covid-19, such as those from Pfizer and Moderna, are nanoformulated. Today there are on the market a hundred nanoformulated drugs all thanks to previous research and development of nanomaterials and nanoparticles over the last three decades.

The “Observatory of Trends in Medicine of the Future” promoted by the Roche Institute foundation has recently published a Report on Nanomedicine coordinated by Dr. Ramón Martínez Máñez, Professor of Inorganic Chemistry at the UPV and Scientific Director of the Centre for Networked Biomedical Research in Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN) in which Dr. José Becerra, Professor of Cell Biology at the University of Malaga and Principal Researcher at CIBER-BBN, BIONAND and IBIMA, Dr. Pilar Marco, Principal Investigator of the Nanobiotechnology group for the diagnosis (Nb4D) of the IQAC-CSIC and Coordinator of the Nanomedicine Research Program of the CIBER-BBN and Dr. María Jesús Vicent, Chief Researcher of the Therapeutic Polymers Laboratory and coordinator of the Advanced Therapies Area of the Príncipe Felipe Research Center have participated as experts. The report was presented at the IV Conference “Anticipating the Medicine of the Future” on November 30, 2021 where a debate was held by the above mentioned in which various topics related to nanomedicine were discussed, such as its applications and barriers.

Nanomedicine applications of today and tomorrow

Nanomedicine is completely transversal, multidisciplinary and dependent on other disciplines, so its applications are multiple and complementary to other branches of knowledge such as artificial intelligence, but the following fields stand out fundamentally.

The design of nanomaterials that improve biocompatibility or biomechanical properties is investigated and can be used for the manufacture of implants that allow replacing portions of diseased tissue and that can even be designed in a personalized way attending to the individual response of each patient, minimizing the risk of rejection by the patient in regenerative medicine.

Nanoparticles are used to build highly sensitive nanodiagnostic platforms, which provide comprehensive biological information easily, quickly and economically at an increasingly early stage. Pilar Marco visualizes a future where “the diagnosis could be our molecular fingerprint, so that the detection of changes in said fingerprint could lead to the detection of a disease before the patient presents symptoms. In turn, this will contribute to prediction and prognosis since, if a large amount of information is available, it can be crossed with genetic information”.

Nanomedicine makes it possible to improve the pharmacokinetics and pharmacodynamics of current drugs, so that they specifically deploy their activity in diseased cells and tissues in a controlled way over time and crossing any biological barrier, which is called controlled drug release. According to Ramón Martínez “Any disease can be susceptible to use these systems to deliver a drug in the appropriate organ or tissue with the reduction of drug doses and side effects.”

Finally, nanotechnology methods facilitate the fusion of diagnosis and therapy in the new medical field of theragnostic; diagnose and treat at the same time by understanding the biological response to treatments, that is, the administration of drugs whose molecules allow visualize how the drug is working.

Barriers faced by nanomedicine

In addition to the difficulties presented by nanomedicine in matters of regulation and industrial property, the aforementioned experts agree that one of the most important challenges is the standardization of manufacturing procedures and quality controls, investment is needed in infrastructures to fine-tune manufacturing and standardization systems (manufacturing of nanoparticles under GMP) and in collaboration with the private sector, which is crucial, to make nanomedicine reach the productive sector and society.

But there are also barriers in the research itself, and funding is needed to break them down. In nanomedicine research, cost / effectiveness analyses have to be focused on the long term. Professor José Becerra explains it very clearly: “Research topics become fashionable and it happens frequently that the years go by and administrations “get tired” of financing a certain field and this is a problem because if a tree is planted by a person who knows It takes ten years to bear fruit, this person has to take care of the tree, but if we give the tree care to someone who does not know about trees, probably this person will abandon the tree in five years … Scientific policies have to persevere in financing nano and accompany it with an improvement in the regulation of products and only then will companies invest in this area”.

At the end of the debate, Professor José Becerra celebrated that the Carlos III Health Institute opted, fifteen years ago, for the creation of a CIBER in Bioengineering, Biomaterials and Nanomedicine, as a tool for scientific policy, he also mentioned the NANBIOSIS platform created by CIBER-BBN, CCMIJU and BIONAND, recognized as ICTS by the Ministry and available for companies and researchers to produce and characterize bio and nanomaterials, and stated that “it is evident that it is not possible to advance in the transfer of knowledgy from nano to the clinic at the same rate as is done in other knowledge areas but to take care of this project is essential”.

The Nanomedicine Revolution

informe sobre nanomedicina

‘Point-of-care or PoC’ devices are able to directly detect the genetic material of the virus in just 30 minutes

A more effective nanomedicine has been developed for the treatment of Fabry rare disease

Nanomedicine: how to get drugs to the place where they have to act.

A new generation of devices for the rapid, cheap and easy diagnosis of candidemia

New Nanomedicines for the topical treatment of complex wounds

Sources of information:

Nanomedicine (European Nanotecnology Platform)

IV Jornada Anticipando la Medicina del Fututo

Nanomedicine Report

Nanomed Spain

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‘SAFE-N-MEDTECH’ and ‘PHOEHIX’ OITBs in CIBER-BBN and NANBIOSIS annual Conference.

National and international leading researchers met online last November 15 and 16 at the XV CIBER-BBN Annual Congress to discuss the latest advances in bioengineering, biomaterials and nanomedicine research, and promote further collaborations in the field.

This year’s CIBER-BBN Annual Conference included three plenary lectures given by internationally recognized experts in the fields of SARS-CoV-2 infection and vaccination, biomedical signal processing for sleep disorders, and regenerative medicine and biosensors. In addition to a selection of internal collaborations, valorization projects and collaboration projects with the CIBER of Oncology, the three programs of the Precision Medicine Infrastructure (IMPaCT) were presented.

NANBIOSIS ICTS contributed to the scientific program of the Conference with a session dedicated to the Open Innovation Test Beds (OITBs). More precisely, Dr. Ángel del Pozo, from Biokeralty presented the SAFE-N-MEDTECH OITB as an example of innovation booster for medical devices, while Dr. Emre Türeli, from MyBiotech GmbH, was invited to describe PHOENIX, a Pharmaceutical OITB for Enabling Nano-pharmaceutical Innovative Products.

Both OITBs’ scope is to cover the gap between research in nanomedicine and clinical practice. Their main objective is to provide the research community and the rest of stakeholders with a fully functional infrastructure for the testing, validation and upscaling of new nano-pharmaceuticals and medical devices through a single entry point.

NANBIOSIS is participating in SAFE-N-MEDTECH leading the corner stone work-package of preclinical validation of nano-enabled medical technologies and also contributing to their previous physico-chemical characterization. Besides that, it coordinates a Test Case about innovative nanostructured implants for bone repair, and participates in three more, all proposed by industrial partners of the project.

CIBER-BBN is participating in Phoenix OITB, as well, with the Unit 6 of NANBIOSIS ICTS (Biomaterials Processing and Nanostructuring Unit) at the Institute of Materials Science in Barcelona (ICMAB-CSIC) as well as the BioNanoSurf group at the Aragon Institute of Materials Science (INMA-CSIC).

These projects have received funding from the European Union’s Horizon 2020 Research and Innovation Programme under Grant Agreements No. 814607 (SAFE-N-MEDTECH) and No. 953183 (PHOENIX)

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Nanomedicine in the Medicine of the Future

Scientists of CIBER-BBN and NANBIOSIS ICTS have participated in the 4th Conference “Anticipating the Medicine of the Future”, which took place on November 30th, organized by the Roche Institute Foundation. The topics for this ediction had been identified by the Observatory of Trends in the Medicine of the Future: Pharmacogenomics, Nanomedicine and Epigenomic

The event counted with three roundtables for discussion in relation to the three topics. The second one, on Nanomedicine, was moderated by Joaquín Arenas, Director of the Research Institute of the 12 de Octubre University Hospital.

Ramón Martínez Máñez, Professor of Inorganic Chemistry at the Interuniversity Research Institute for Molecular Recognition and Technological Development (IDM) of the Polytechnic University of Valencia and Scientific Director of CIBER-BBN and Unit 26 of NANBIOSIS gave a talk entitled “Macro problems, nano solutions”. After that, the debate was openwith the participation of Maria Pilar Marco, Research Professor of the Spanish Council for Scientific Research (CSIC) and Coordinator of the Nanomedicine Research Program CIBER-BBN and Scientific Director of unit 2 of NANBIOSIS, CAbS, José Becerra, Emeritus Professor of of Cell Biology of the University of Malaga and Principal Investigator of CIBER-BBN, BIONAND and IBIMA and Maria Jesús Vicent, Coordinator of the Advanced Therapies Area of the Principe Felipe Research Center.

The Roundtable discussed the applications of nanomedicine in the Medicine of the Future and in Personalized Precision Medicine, as well as the challenges facing nanomedicine.

The Observatory of Trends in the Medicine of the Future, promoted by the Roche Institute Foundation, aims to generate and disseminate knowledge in areas of incipient knowledge related to Personalized Precision Medicine and that are part of the Medicine of the Future.

In this context, the fundation Instituto Roche has recently published a report on nanomedicine coordinated by Ramón Martínez in which José Becerra, María Pilar Marco and María Jesús Vicent have participated as experts.

Currently, nanoparticles or nanostructures are being applied for the controlled release of drugs in cancer and other pathologies and nanodevices for the diagnosis of diseases or the development of nanomaterials for applications in regenerative medicine. In the coming years, and with the translation into clinical practice of more and more developments based on these technologies, nanomedicine will contribute to the medicine of the future approaching the diagnosis and treatment of diseases earlier, more efficiently and in a more efficient and personalized way.