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Nanoparticles to eradicate Cancer Stem Cells

Colorectal cancer (CRC) has a high prevalence worldwide and resistance to conventional chemotherapies and tumor relapse are usually related with a population of cells with malignant properties – Cancer Stem Cells (CSC).

Scientists of CIBER-BBN and VHIR have led a research with the goal not only to treat the primary CRC, but also eradicate CSC. For both purposes, the use of nanoparticles (NP) is a useful strategy. These “bullets” carrying a drug in its core, are able to reach tumor tissue due to its small size. Cancer cells, and in particular CSC, present at their surface receptors that could be specifically recognized by molecules used to decorate NP, driven the drug of interest to these cells. In this work we developed a type of NP decorated with an antibody fragment that specifically recognize the receptor CD44v6, which is overexpressed in CSC and was previously demonstrated to be present in patients with metastasis and poor-prognosis. Moreover, researchers have encapsulated Niclosamide (NCS), a drug that demonstrated efficacy against breast CSC, inside their NP.  NP increased the efficacy of NCS and​ accumulated in the tumors reducing its systemic exposure and increasing safety. Most importantly, the developed system significantly reduce circulating tumor cells, precursors of metastasis, reducing CSC malignancy.

This system has the potential to create a new therapeutic approach that could bring a new hope for CRC treatment and prevention of cancer relapse.​

The work has been developed at the group of CIBBIM-Nanomedine_Drug Deliver & Targeting of Vall d’Hebron Institute of Research (VHIR) and CIBER-BBN, in collaboration with Bruno Sarmento (University of Porto, Portugal) and Marika Nestor (Uppsala University, Sweden) that helped to developed the NP and the targeting antibody, respectively. In vivo assays on the safety and efficacy of the NPs were conducted thanks to the contribution of the FVPR/U20 of ICTS-Nanbiosis. ​

Article of reference

Fernanda Andrade, Diana Rafael, Mireia Vilar-Hernández, Sara Montero, Francesc Martínez-Trucharte, Joaquin Seras-Franzoso, Zamira V.Díaz-Riascos, Ana Boullosa, Natalia García-Aranda, Patricia Cámara-Sánchez, Diego Arango, Marika Nestor, bane Abasolo, Bruno Sarmento, Simó SchwartzPolymeric micelles targeted against CD44v6 receptor increase niclosamide efficacy against colorectal cancer stem cells and reduce circulating tumor cells in vivo Journal of Controlled Release Volume 331, 10 March 2021, Pages 198-212 https://doi.org/10.1016/j.jconrel.2021.01.022

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Design and engineering of tumor-targeted, dual-acting cytotoxic nanoparticles

In the frame of the collaboration of three units of NANBIOSIS, researchers of CIBER-BBN Groups proposed a strategy to simultaneously deliver anticancer drug pairs, composed by a tumor-targeted protein nanoparticle and an antiproliferative drug, with specific activ-ity for the same type of cancer.

These three units are:

The results on the investigation have been published in an article entitled “Design and engineering of tumor-targeted, dual-acting cytotoxic nanoparticles”· by Acta Biomaterialia

The researchers have explored the possibility to conjugate tumor-targeted cytotoxic nanoparticles and conventional antitumoral drugs in single pharmacological entities using CXCR4-targeted self-assembling protein nanoparticles based on two potent microbial toxins, the exotoxin A from Pseudomonas aeruginosa and the diphtheria toxin from Corynebacterium diphtheriae, to which oligo-floxuridine and monomethyl auristatin E respec- tively have been chemically coupled.

The resulting multifunctional hybrid nanoconjugates, with a hydro- dynamic size of around 50 nm, are stable and internalize target cells with a biological impact. Although the chemical conjugation minimizes the cytotoxic activity of the protein partner in the complexes, the concept of drug combination proposed is fully feasible and highly promising when considering multiple drug treatments aimed to higher effectiveness or when facing the therapy of cancers with acquired resistance to classical drugs.

Thus, these results open a wide spectrum of opportunities in nanomedical oncology.

Article of reference:

Eric Voltà-Durán, Naroa Serna, Laura Sánchez-García, Anna Aviñó, Julieta M. Sánchez, Hèctor López-Laguna, Olivia Cano Garrido, Isolda Casanova, Ramón Mangues, Ramon Eritja, Esther Vázquez, Antonio Villaverde, Ugutz Unzueta Design and engineering of tumor-targeted, dual-acting cytotoxic nanoparticles. Acta Biomaterialia, Volume 119, 1 January 2021, Pages 312-322), 57746-57756 https://doi.org/10.1016/j.actbio.2020.11.018 

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12th Workshop on Magnetic Resonance Spectroscopy and Imaging (MRI/MRS) Applied to Laboratory Animals

We are glad to inform that registration is now open for the 12th Workshop on Magnetic Resonance Spectroscopy and Imaging (MRI/MRS) Applied to Laboratory Animals, organized by the Biochemistry and Molecular Biology Department (UAB) and the Nuclear Magnetic Resonance Facility, which is also part of the NANBIOSIS ICTS U25 NMR: Biomedical Applications I. Workshop will take place February 15-18th, 2021.
This course combines a comprehensive series of lectures on the technology of Magnetic resonance spectroscopy and imaging (MRS/MRI) with hands-on laboratory sessions to provide practical demonstrations of key concepts and procedures for preclinical studies.
Whether you are considering MRI as a research tool in your lab or just would like to learn more about MRI, this workshop addresses practical aspects of experimental MRI with laboratory animals and provide valuable hands-on experience on a 7 Tesla Bruker BioSpec spectrometer.

Online registration:
(http://sermn.uab.cat/wiki/doku.php?id=formulari_curs_mri_mrs)

For more detailed information, please go to:
http://sermn.uab.cat/2021/01/12th-workshop-mrs-mri-small-animals/

Please note that a limited number of attendants is currently allowed (maximum 4). Anticipated reservation is strongly recommended.

See the workshop brochure 

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New spin off of VHIR “BSURE Medical” led by Simó Schwartz (NANBIOSIS U20)

Dr. Simó Schwartz, Scientific Director of NANBIOSIS U20 and head of the “Drug Delivery and Targeting group” of CIBER-BBN and VHIR, toghether with Dr. Jaume Alijotas (VHIR), have promoted the creation of the Spin-off ·BSURE Medical· for the devlopment of products and services for the diagnosis, prevention and consultation of aspects related to treatments with all types of bioimplants.

One of the objectives of the Drug Delivery and Targeting group is to carry out preclinical studies to determine the effects and toxicities of drug delivery systems, cell therapies and biomaterials. Studies chace been carried out through the Nanbiosis unit U20, of which the CIBBIM-Nanomedicine platform for functional validation and preclinical studies (FVPR) is a part. The group’s interest in studying the immune-related adverse effects caused by different biomaterials, allowed the identification and validation in two clinical studies of the predictive use of specific genetic biomarkers associated with severe late responses caused by injectable biomaterials, the basis of the new company BSure Medical.

Dr. Jaume Alijotas and Simó Shwartz have led the development of a procedure that makes it possible to determine, reliably and easily the risk of suffering serious late-onset immune, local, regional or systemic adverse effects (edema, angioedema, induration of skin, multiple inflammatory nodules, panniculitis, even granulomatous or autoimmune diseases…) after implantation of an injectable biomaterial, such as dermal or subcutaneous fillers. This risk is strongly associated with the presence of certain antigen profiles in a biological sample of the individual, which allows them to be easily identified from the analysis of blood or saliva samples.

The technology is patented and has been validated in two independent clinical trials coordinated by the Systemic Autoimmune Diseases Unit of the Vall d’Hebron University Hospital in Barcelona and by the Dermatology Department of the Erasmus Medical Center, Rotterdam and the Department of Plastic Surgery, VU University Medical Center, Amsterdam. The VHIR has granted BSURE a license to use and exploit it exclusively and worldwide. The patent has already been granted in Europe, Brazil and Japan

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Encapsulation of BSA/alginate water–in–water emulsions by polyelectrolyte complexation

Researchers of NANBIOSIS U12. Nanostructured liquid characterization unit from CIBER-BBN and IQAC-CSIC have recently published an article entitled Encapsulation of BSA/alginate water–in–water emulsions by polyelectrolyte complexation in the scientific journal Food Hydrocolloids

The research which results are published involves the encapsulation of drops of water-in-water emulsions, which could be used as vehicles for the administration of active principles.

Characterization of emulsions and capsules was performed in the Unit 12 of NANBIOSIS Nanostructured Liquid Characterization Unit.

Water-in-Water (W/W) emulsions were prepared in aqueous mixtures of an anionic polyelectrolyte (sodium alginate, NaAlg), with a globular protein (bovine serum albumin, BSA). This combination showed phase separation at two different intervals of pH, and their phase behavior was studied. BSA-in-alginate emulsions were obtained and dropped into Ca2+, Fe3+ or chitosan solutions, forming capsules with diameters around 2–4 mm, by ionic complexation of sodium alginate, located in the continuous phase of the emulsions. The results showed a strong dependence on the cation or polycation. Capsules prepared with Ca2+ were not robust and collapsed during freeze-drying, while Fe3+ induced the gelation of the interior of capsules, even at short (5 min) contact time. Better results were obtained when encapsulating with chitosan and applying longer immersion times. In these capsules, the liquid interior contained well-preserved BSA-in-alginate emulsions droplets, identical to the initial emulsions before encapsulating. Freeze-dried spherical capsules prepared with alginate/Fe3+ or alginate/ chitosan shells had smooth surfaces, and a highly porous interior, templated by the presence of W/W emulsion droplets.

Article:

M. Michaux, N. Salinas, J. Miras, S. Vílchez, C. González-Azón, J. Esquena,
Encapsulation of BSA/alginate water–in–water emulsions by polyelectrolyte complexation, Food Hydrocolloids, Volume 113, 2021, 106406,

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Smart-4-Fabry final workshop

Next Wedneday, February 3, 2021 will take place the on-line event Smart-4-Fabry Final Workshop.  

Smart-4-Fabry is a european project, coordinated by CIBER-BBN wich has been developed during four years. This project is a sign of cooperation at European level to boost nanomedicine development and translation to clinical stages.

This project is also a clear example of the relevance of access to advanced research infrastructures as NANBIOSIS -ICTS. Four NANBIOSIS units have collaborated and contributed to Smart-4-Fabry development:

“The Fabry disease (FD) is a lysosomal storage disorder (LSD) that currently lacks an effective treatment” as Prof. Nora Ventosa, IP of the project, explained for NANBIOSIS blog – The aim of Smart-4-Fabry is to obtain a new nanoformulation of GLA, that will improve the efficacy and toleration compared to the actual treatment with non-formulated GLA.

In the final workshop experts will talk about how, why and for what the solution proposed by Smart4Fabry was conceived.

Registrations and program at https://smart4fabry.cientifis.com/

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New Center for Research in Advanced Pharmaceutical Development

The NanoBioCel Research group, led by Jose Luis Pedraz, from CIBER-BBN and UPV/EHU, group that coordinates the Unit U10 Drug Formulation of NANBIOSIS -ICTS, together with the Provincial Council of Álava and the Center for Technological Research and Development TECNALIA, have launched last Thursday, January 21, the new Center for Research in Advanced Pharmaceutical Development, which will be located in the Lascaray Building, on the Álava campus of the UPV / EHU.

The objective of this center is to introduce new technologies in the pharmaceutical field and promote applied research in 3D Bio-printing, 3D Printing of medical devices and 3D Printing of new drugs.

This new center is a strategic and ambitious project, supported directly by the Provincial Council of Álava with a budget of € 2,500,000 that seeks to integrate the Álava region within the strategy proposed by the European Union in biosciences and technological development, sectors that have been boosted in the new investment initiative in response to the Coronavirus. This center is also a regional reference as a result of the leadership exercised by the NanoBioCel research group and a fruitful relationship of common projects to offer services to the pharmaceutical industry with Tecnalia2.

In the picture: Jose Luis Elejalde from Tecnalia, Javier Hernando from the Provincial Council of Alava, Pilar Garcia de Salazar, Lieutenant General Deputy and Provincial Deputy for Economic Development and Territorial Balance in the Provincial Council of Alava. Jose Luis Martin, Vice-Rector for Research of the UPV / EHU and Jose Luis Pedraz, IP NanoBioCel group.

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Electrocardiogram-Derived Tidal Volume During Treadmill Stress Test

Researchers of BSICoS Group and NANBIOSIS ICTS U27 High Performance Computing from CIBER-BBN and I3A-UZ have published a new article in the scientific journal IEEE Transactions Biomedical Engineering. proposing a new method to estimate tidal volume during stress test based only on the electrocardiogram signal.

Electrocardiogram (ECG) has been regarded as a source of respiratory information with the main focus in the estimation of the respiratory rate. Although little research concerning the estimation of tidal volume (TV) has been conducted, there are several ECG-derived features that have been related with TV in the literature, such as ECG-derived respiration, heart rate variability or respiratory rate.

In this work, resarchers exploited these features for estimating TV using a linear model. 25 young (33.4 ± 5.2 years) healthy male volunteers were recruited for performing a maximal (MaxT) and a submaximal (SubT) treadmill stress test, which were conducted in different days. Both tests were automatically segmented in stages attending to the heart rate. Afterwards, a subject-specific TV model was calibrated for each stage, employing features from MaxT, and the model was later used for estimating the TV in SubT.

During exercise, the different proposed approaches led to relative fitting errors lower than 14% in most of the cases and than 6% in some of them. Low achieved fitting errors suggest that TV can be estimated from ECG during a treadmill stress test. The results suggest that it is possible to estimate TV during exercise using only ECG-derived features.

Article of reference:

Milagro, J; Hernando, D; Lázaro, J; Casajús, J A; Garatachea, N; Gil, E; Bailón, R. Electrocardiogram-Derived Tidal Volume During Treadmill Stress Test
IEEE Transactions Biomedical Engineering, 67 (1), 2020. DOI: 10.1109/TBME.2019.2911351

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Hybridization of men and machines, with Rosa Villa

Prof. Rosa Villa, Scientific Director of NANBIOSIS U8 Micro– Nano Technology Unit, and group leader of the research group of biomedical applications of ICNM–CSIC and CIBER-BBN, has participated in the program of National Radio of Spain “The Open Future: Biobots” led by Tato Puerto.

Following the recent presentation by a team of American scientists of the design of “reprogrammable organisms”, halfway between a robot and a living being, that is, an extraordinary living machine made from frog cells, the program of National Radio of Spain called “Open Future” has dedicated a session to explain what are “Biobots” and to generate debate and reflexion with experts like Prof, Rosa Villa.

Asked about the current outlook and futute of the “Hybridization of men and machines“, Rosa Villa has explained that in the area of ​​micro and nanotechnology, (where her group works), the hybridization takes place to make neural interfaces, to interrelate with the human brain registering many more signals from the brain and being able to offer patients greater mobility for artificial prosthetics or even other human enhancement activities. The main problem for this at a technological level is that a series of biological and material processes have to be carried out while these processes need to be easilly integrated by the human body. The functioning of the brain is still very unknown, the brain is a very closed box, very well protected and inaccessible but the amount of signals that are registered is spectacular. The latest technologies and materials, such as graphene, make it possible to build sensors with smaller electrodes that allow many signal points to be recorded in the brain at the same time, with a signal quality that was not possible to reach until now which allows scientists to know a series of high and low frequency signals that give very useful information from the brain, not only to know how it works, but also to predict diseases such as epilepsy or Alzheimer’s.

The program can be listen here, in Spanish

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Nucleic Acids Chemistry, new book release by Ramon Eritja

Ramón Eritja, Scientific Director of NANBIOSIS Unit 29 Oligonucleotide Synthesis Platform (OSP) has just published a new book “Nucleic Acids Chemistry, modifications and conjugates for Biomedicine and Nanotechnology“, Anna Avinó, Scientific Coordinator of NANBIOSIS Unit 29 is also a writer of the book.

The book “Nucleic Acids Chemistry” takes the most important aspects of the methodology of oligonucleotides synthesis, that is currently expanding by the endorsement of a dozen of new medicines, such as the first medicine based on interfering RNA for the control of LDL and cholesterol in blood that will facilitate the decrease of cardiovascular illnesses.

The writing of the book has been directed by Dr. Ramon Eritja, of Centro de Investigación en Red de Nanomedicina (CIBER-BBN) and is Research Professor at Institute of Advanced Chemistry of Catalonia (IQAC-CSIC), being its director between 2012-2017. The co-authors are Carme Fàbrega, Anna Aviñó, Santiago Grijalvo, Andreia F. Jorge, from IQAC-CSIC, Carlos González from Instituto de Química Física Rocasolano (IQFR-CSIC) and Raimundo Gargallo from University de Barcelona  The book began to be written in mid-2019, although most of the book was written during the lockdown.

In the last five years, an expansion of technologies based on DNA and RNA in diagnosis and therapeutic use has been produced, and it has been very important in the research of quick solutions to avoid the COVID pandemic and, predictably, the research group’s environment has led the development of several solutions, like biosensors for the direct detection of SARS-CoV-2.

A former PhD student of Ramon Eritja group, Dr. Ramón Güimil García, Head of Synthetic Oligonucleotides bei BioNTech, has participated in the development of the BioNTech-Pfizer mRNA vaccine. Another doctor, Brendan Manning, formed member of the group, has participated in the development of a diagnosis kit named Sherlock, which uses the CRISPR-Caspasa system for the detection of the virus that causes COVID.

Dr Erija completed his doctoral thesis at the University of Barcelona directed by Dr. Ernest Giralt on the subject of peptide synthesis. In 1984 he carried out his first postdoc with Dr. Itakura at the Beckman Research Institute of City of Hope in Los Angeles where the production of the first synthetic genes was carried out, highlighting the production of synthetic insulin that, with the name of humulin, solved the problems generated from the use of swine insulin. In 1986 she completed the second postdoc with Dr. Caruthers at the University of Colorado at Boulder. In this laboratory, phosphoramidites were developed, which are the reagents used today for the production of synthetic DNA and RNA. Upon his return to Barcelona, ​​he joined the CSIC Research and Development Center where he organized the first research group in our country focused on oligonucleotide synthesis. In 1984 he moved to the European Molecular Biology Laboratory (EMBL) in Heidelberg (Germany) to direct for 5 years one of the most prestigious groups in DNA and RNA Chemistry in Europe. Upon his return to Barcelona, ​​he was part of the Barcelona Institute for Biomedical Research (IRB Barcelona) and was recognized as a group of excellence by the CIBER-BBN. In 2012 he moved to the IQAC-CSIC to occupy the direction of the institute until 2017.

Refernce:

Nucleic Acids Chemistry – Modifications and Conjugates for Biomedicine and Nanotechnology Edited by: Ramon Eritja. De Gruyter | 2021 DOI: https://doi.org/10.1515/9783110639537

The book can be purchased here: link

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