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News U20

News U20

NANBIOSIS research to fight cancer

Twenty years ago, the 4 February was declared World Cancer Day with the global challenge of cancer would not be forgotten. Since then, huge progress has been made to understand, prevent, diagnose, and treat cancer.

NANBIOSIS as an ICTS (Singular Scientific and Technical infrastructures) for biomedical research plays a very important role in the fight against cancer. Some examples of the work carried out during the last year, are bellow:

Unit 20 of NANBIOSIS  at VHIR, works in several proyects reletaed to cancer as  H2020-NoCanTher: magnetic nanoparticles against pancreatic cancer through the use of hyperthermia combined with conventional treatment. H2020-Target-4-Cancer: nanotherapy based on polymeric micelles directed against specific receptors of tumor stem cells in colorectal cancer. H2020-DiamStar: nanodiamonds directed against leukemia for the potentiation of chemotherapy. FET-OPEN EvoNano: in silico and tumor-tumor models for the prediction of PK / PD and tumor efficacy of antitumor nanomedicines against tumor stem cells.

The activities of U1 of Protein Production Platform (PPP) are also strongly committed with several projects devoted to develop new, more selective and more efficient antitumoral drugs, with antimetastatic effects.
oordinated action between units U1 of Protein Production Platform (PPP),
U18 of Nanotoxicology and U29 of Nucleic Acid Synthesis, shows promising results in development of nanopharmaceuticals with a high degree of efficacy for the treatment of metastases in colon cancer

Unit 6 of NANBIOSIS Biomaterial Processing and Nanostructuring Unit  is also working on a joined initiative between CIBER-BBN and CIBER-ONC to improve the current ex vivo immune cell expansion systems to help introduce immunotherapies such as the adoptive cell therapies, which have shown complete remissions of terminal cancer patients, to the clinics overcoming the limitation of having enough therapeutic cells with novel Nanobiomaterials. Researchers of Unit 6 and researchers of Laboratory of Translational Research in Child and Adolescent Cancer from the Vall d’Hebron Research Institute (VHIR), are working on a project financed by the Spanish Government and CIBER-BBN, for the development of a new nanomedicine for the treatment of high-risk neuroblastoma, one of the most frequent childhood cancers.

In our unit U26. NMR: Biomedical Applications II,  several studies for cancer biomarker discovery are being carried out. NMR studies on biofluids for the design of novel strategies for diagnosis support, easily transferable into the clinical practice, are being developed in biofluids in the context of cancer. Urine is one of the most easily obtainable biofluid and is a non-invasive source of biomarkers. Among these studies, we can mention the good discrimination achieved between urine from bladder cancer patients before surgery (cancer) and urine after surgery (free of cancer) and in the follow up of the disease, to monitor relapses

Some of the results of these researchs have been published in scientific magazines of high impact as for exemple;

Integrative Metabolomic and Transcriptomic Analysis for the Study of Bladder Cancer Alba Loras, Cristian Suárez-Cabrera, M. Carmen Martínez-Bisbal, Guillermo Quintás , Jesús M. Paramio, Ramón Martínez-Máñez,
Salvador Gil and José Luis Ruiz-Cerdá. Cancers 2019, 11, 686; doi:10.3390/cancers11050686

Nanostructured toxins for the selective destruction of drug-resistant human CXCR4+ colorectal cancer stem cells Naroa Serna, Patricia Álamo, Prashanthi Rameshef, Daria Vinokurovaef, LauraSánchez-García, Ugutz Unzueta, Alberto Gallardo, María  Virtudes Céspedes, Esther Vázquez, Antonio Villaverde, Ramón Mangues, Jan Paul Medema. . Journal of Controlled Release.  Volume 320, 96-104, 2020 https://doi.org/10.1016/j.jconrel.2020.01.019

Controlling self-assembling and tumor cell-targeting of protein-only nanoparticles through modular protein engineering Voltà-Durán, E., Cano-Garrido, O., Serna, N. et al. CSci. China Mater.63, 147–156 (2020). https://doi.org/10.1007/s40843-019-9582-9

Engineering Secretory Amyloids for Remote and Highly Selective Destruction of Metastatic Foci, María Virtudes Céspedes  Olivia Cano‐Garrido  Patricia Álamo  Rita Sala  Alberto Gallardo  Naroa Serna  Aïda Falgàs  Eric Voltà‐Durán  Isolda Casanova  Alejandro Sánchez‐Chardi  Hèctor López‐Laguna  Laura Sánchez‐García  Julieta M. Sánchez  Ugutz Unzueta  Esther Vázquez  Ramón Mangues  Antonio Villaverde . Advanced Materiasls Número de artículo: 1907348 , Dec. 2019 https://doi.org/10.1002/adma.201907348

Artificial Inclusion Bodies for Clinical Development 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, Advanced Science. 2019 https://doi.org/10.1002/advs.201902420

Nanostructured Nucleolin-Binding Peptide for Intracellular Drug Delivery in Triple-Negative Breast Cancer Stem Cells Mireia Pesarrodona, Laura Sánchez-García, Joaquin Seras-Franzoso, Alejandro Sánchez-Chardi, Ricardo Baltá-Foix, Patricia Cámara-Sánchez, Petra Gener,  José Juan Jara, Daniel Pulido, Naroa Serna, Simó Schwartz Jr. Miriam Royo, Antonio Villaverde, Ibane Abasolo, Esther Vazquez ACS Applied Materials & Interfaces DOI: 10.1021/acsami.9b15803  

Nanostructure Empowers Active Tumor Targeting in Ligand‐Based Molecular Delivery López‐Laguna, H., Sala, R., Sánchez, J. M., Álamo, P., Unzueta, U., Sánchez‐Chardi, A., Serna, N., Sánchez‐García, L., Voltà‐Durán, E., Mangues, R., Villaverde, A., Vázquez, E., . Part. Part. Syst. Charact. 2019, 36, 1900304. https://doi.org/10.1002/ppsc.201900304

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Targeting antitumoral proteins to breast cancer by local administration of functional inclusion bodies

Three units of NANBIOSIS have collaborated in obtaining the research results published in the article “Targeting Antitumoral Proteins to Breast Cancer by Local Administration of Functional Inclusion Bodies” published by Advanced Science

Protein production and DLS have been partially performed by the Unit 1 of ICTS NANBIOSIS Protein Production Platform (PPP) and the Unit 6 NANBIOBIS Biomaterial Processing and Nanostructuring Unit. Biodistribution and immunohistochemistry assays were performed at NANBIOSIS U20 In Vivo Experimental Platform/FVPR

Two structurally and functionally unrelated proteins, namely Omomyc and p31, are engineered as CD44‐targeted inclusion bodies produced in recombinant bacteria. In this unusual particulate form, both types of protein materials selectively penetrate and kill CD44+ tumor cells in culture, and upon local administration, promote destruction of tumoral tissue in orthotropic mouse models of human breast cancer. These findings support the concept of bacterial inclusion bodies as versatile protein materials suitable for application in chronic diseases that, like cancer, can benefit from a local slow release of therapeutic proteins.

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AKT2 as a promising target for future anti-cancer therapies

The researchers of NANBIOSIS U20, led by Ibane Abásolo and Simó Schwartz have published a new article on the scientific magazine Cancerswith the title Pivotal Role of AKT2 during Dynamic Phenotypic Change of Breast Cancer Stem Cells

All the in vivo studies were performed by NANBIOSIS U20 In Vivo Experimental Platform.

Therapeutic resistance seen in aggressive forms of breast cancer remains challenging for current treatments. More than half of the patients suffer from a disease relapse, most of them with distant metastases. Cancer maintenance, resistance to therapy, and metastatic disease seem to be sustained by the presence of cancer stem cells (CSC) within a tumor. The difficulty in targeting this subpopulation derives from their dynamic interconversion process, where CSC can differentiate to non-CSC, which in turn de-differentiate into cells with CSC properties. Using fluorescent CSC models driven by the expression of ALDH1A 1(aldehyde dehydrogenase 1A1), we confirmed this dynamic phenotypic change in MDA-MB-231 breast cancer cells and to identify Serine/Threonine Kinase 2 (AKT2) as an important player in the process. To confirm the central role of AKT2, we silenced AKT2 expression via small interfering RNA and using a chemical inhibitor (CCT128930), in both CSC and non-CSC from different cancer cell lines. Our results revealed that AKT2 inhibition effectively prevents non-CSC reversion through mesenchymal to epithelial transition, reducing invasion and colony formation ability of both, non-CSC and CSC. Further, AKT2 inhibition reduced CSC survival in low attachment conditions. Interestingly, in orthotopic tumor mouse models, high expression levels of AKT2 were detected in circulating tumor cells (CTC). These findings suggest AKT2 as a promising target for future anti-cancer therapies at three important levels: (i) Epithelial-to-mesenchymal transition (EMT) reversion and maintenance of CSC subpopulation in primary tumors, (ii) reduction of CTC and the likelihood of metastatic spread, and (iii) prevention of tumor recurrence through inhibition of CSC tumorigenic and metastatic potentia

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NANBIOSIS U20 at the Nanomed Europe Conference, NME19.

Last week took place in Braga, Portugal, the Nanomed Europe Conference, NME19, a new and unique conference  born from the merge of the 14th annual event of the ETPN & the European scientific conference ENM (after London 2017 & Grenoble 2015), bringing together scientists, technology providers, entrepreneurs, industry and clinicians, all of them developing great medical applications of Nanotechnologies and emerging MedTech. The event is been co-organized this year by the ETPN and INL.

Simó Schwartz, Scientific Director of NANBIOSIS U20, was one of the selected speakers and gave a lecture about “Preclinical development of magnetic nanoparticles for the treatment of pancreatic cancer”

Two posters mentioning the research carried out at NANBIOSIS Unit 20 were also presented. (See the picture)

It was also a ood opportunity to explain the advances in the two H2020 projects where NANBIOSIS U20 participates (“Nocanther” and “Smart4Fabry”), and also an internal project, “Meridian”, on the use of exosomes (with own patent and financed by the FIS).

In Nocanther Project, the U20 participates providing the animal models and the imaging techniques (X-ray CT images) for the biodistribution and efficacy assays of iron oxide nanoparticles. These assays are essential for preparing the dossier for the clinical application of these nanoparticles. Indeed, patient recruitment for clinical studies on Nocanther project will start in 2020.

In Smart4Fabry, the U20 works completing the efficacy assays of different nanoGLA formulations. Again, these efficacy assays will be a necessary step before starting preclinical regulatory assays.

In the MERIAN project, U20 provides the in vivo proof-of-concept and biodistribution assays that support the use of protein loaded exosomes as a feasible product for treating lysosomal storage disorders.

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Preclinical molecular imaging and its application to biomedical research

During the days 22-24 of May is taking place in Madrid the 3rd Workshop of introduction to the preclinical molecular image and its application to biomedical research,. The wokshop has been organized by the Health Research Institute of the Gregorio Marañón Hospital, the Complutense University of Madrid and the Madrilenian Network of nanomedicine in molecular imaging (RENIM-CM).

The program counts with theoretical sessions of introduction to the physical foundations of each one of the modalities of image and its applications to preclinical biomedical research, as well as practical demonstrations of said image techniques.

Ibane Abásolo, Scientific Coordinator of Unit 20 of NANBIOSIS In Vivo Experimental Platform, introduced the in vivo optical imaging applications, explaining the research carried out at her research group at Vall d’Ebron Hospital Research Institute (VHIR) and NANBIOSIS U20 created by CIBER-BBN and VHIR, applied to projects as the H2020 Smart4Fabry and NoCanTher

NANBIOSIS U20 In vivo Experimental Platform has three different sections, a Molecular Imaging section for in vivoex vivo and in vitro imaging studies (fluorescence, bioluminescence and X-rays), a preclinical animal model section and a preclinical histology section.

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NANBIOSIS Scientific Women in the International Day of Women and Girls in Science

Today February 11 is the International Day of Women and Girls in Science, a day to raise awareness of the gender gap in science and technology.

According to the United Nations, while yet women and girls continue to be excluded from participating fully in science, science and gender equality are vital to achieve the internationally agreed development goals, including the 2030 Agenda for Sustainable Development. Thus, in recent years, the international community has made a great effort to inspire and promote the participation of women and girls in science.

NANBIOSIS wants to acknowledge  the efforts made by scientific women who struggle every day to contribute their bit to Science and highlight their essential role in nowadays research. Especially we want to recognize the work of scientists women involved in our units, whatever is the nature of their contribution: technical, scientific development, management, coordination, direction, etc; just to mention some examples:
Neus Ferrer in the Scientific Direction of Unit 1 Protein Production Platform (PPP)
Pilar Marco and Nuria Pascual in the Management and Scientific Coordination of U2 Custom Antibody Service (CAbS) 
Miriam Royo in the Scientific Direction of U3 Synthesis of Peptides Unit
Laura Lechuga and M.Carmen Estevez in the Direction and Scientific Coordination of U4 Biodeposition and Biodetection Unit
Nora Ventosa and Nathaly Segovia in the Scientific Direction and Technical Coordination of U6 Biomaterial Processing and Nanostructuring Unit
Isabel Oliveira and Teresa Galán in the Coordination of U7 Nanotecnology Unit
Rosa Villa and Gemma Gabriel in the Management and Scientific Coordination of U8 Micro – Nano Technology Unit
Gema Martínez in the Scientific Coordination of U9 Synthesis of Nanoparticles Unit
Fany Peña in the Scientific Coordination of U13 Tissue & Scaffold Characterization Unit
Mª Luisa González Martín in the of Direction and Scientific Coordination of U16 Tissue & Scaffold Characterization Unit
Gemma Pascual and Isabel Trabado in the Coordination of the U17 Confocal Microscopy Service
Mª Virtudes Céspedes in the Scientific Coordination of U18 Nanotoxicology Unit
Beatriz Moreno in the Scientific Direction of Unit 19 Clinical tests lab
Ibane Abásolo in the Scientific Coordination of Unit 20 In Vivo Experimental Platformt
Verónica Crisóstomo in the Scientific Direction of Unit 24 Medical Imaging 
Ana Paula Candiota in the Scientific Coordination of Unit 25 Biomedical Applications I 
Maria Luisa García in the Scientific Direction of U28 NanoImaging Unit from Bionand, recently incorporated to NANBIOSIS

Thanks to all of you and your teams!

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NANBIOSIS Against Cancer

The World Health Organization, the International Cancer Research Center (IARC) and the International Union Against Cancer (UICC) celebrate February 4 of each year as World Cancer Day

Every year, 14 million new cases of cancer are diagnosed worldwide and the disease causes 8.2 million deaths.

Thanks to scientific research, great advances have been made in the fight against cancer. Through surgery, chemotherapy or radio therapy and, in the last 20 years, through immunotherapy, hormonal treatment or cell therapies, tools have been obtained to improve early diagnosis and treatments, increasing cancer survival by 20%.

The only way to understand cancer and, someday, eradicate it or eliminate the suffering and death due to this disease, is RESEARCH

NANBIOSIS as an ICTS (Singular Scientific and Technical Infrastructures) for biomedical research plays a very important role in the fight against cancer. Some examples are bellow:

Thanks to a coordinated action between units U1 of Protein Production Platform (PPP), U18 of Nanotoxicology and U29 of Nucleic Acid Synthesis, NANBIOSIS is developing nanopharmaceuticals with a high degree of efficacy for the treatment of metastases in colon cancer, by using of proteins with high specificity of binding to metastatic cells and a high degree of permanence in the blood flow, loaded with anti-cancer drugs that are selectively released inside the tumor cells that are going to form the metastases. Through the public financing of a NEOTEC project and a RETOS-COLABORACION and the company NANOLIGENT SL, the first antimetastatic drug on the market will be developed.

The Protein Production Platform-PPP collaborates with research projects whose objective is the development of new cancer therapies based on recombinant modular proteins with the ability to self-assemble. These multimeric complexes have shown, in animal models, a high stability in serum and an improved biodistribution compared to that observed with drugs for clinical use. These principles have been valued in different types of cancer, including colorectal cancer and breast cancer. The modular design of these constructions allows the incorporation or substitution of direct peptides and therefore they are presented as a transversal tool for more effective treatments against cancer. In addition, the PPP has served the Vall d’Hebron Institute of Oncology (VHIO) of Barcelona, the Josep Vilanueva group (CIBERONC) in the field of biomarker study and new targets associated with triple negative breast cancer (TNBC).

Unit 6 of NANBIOSIS Biomaterial Processing and Nanostructuring Unit is working on a project in collaboration with VHIR, financed by the Spanish Goverment and CIBER-BBN, for the development of a new nanomedicine for the treatment of high-risk neuroblastoma, one of the most frequent childhood cancers.

Unit 6 is also working on the project Artificial Lymph Nodes for Cancer ImmunoTherapy (ALYCIA) A project born of a initiative of CIBER-BBN/ CIBERONC to enhance scientific interdisciplinary collaborations between research groups working on oncology and nanomedicine. Researchers of unit 6 will develop Artificial Lymph Nodes (ALN) based on dynamic 3D scaffolds able to promote efficient ex vivo lymphatic cell expansion of relevant phenotypes. Such ALN represent a new approach to lymphocyte expansion, which not only includes artificial Antigen Presenting Cells in suspension like the state-of-the-art expansion techniques, but also mimics the function of the LN ex vivo.

One of the singular capabilities of the U25 of NANBIOSIS NMR: Biomedical Applications I is the acquisition of high quality, high resolution preclinical magnetic resonance imaging/spectroscopy/spectroscopic imaging data. This allows performing leading-edge studies in preclinical cancer models such as noninvasive therapy response follow-up in murine brain tumours, revealing new response biomarkers with translational potential for brain cancer patients.

NANBIOSIS U4 Biodeposition and Biodetection Unit  is currently developing the national project PREDICT Point-of-care Nanoplasmonic Platforms for Novel High-Value Diagnostics and Therapy Follow-Up , which works in the early detection of lung cancer. PREDICT project will use the Unit 4 of Nanbiosis for the multiplexed biofunctionalization of the biosensor chips and their methodology optimisation.

Finally, Unit 20 of NANBIOSIS In Vivo Experimental Platform at VHIR, is the most implicated of the CIBER units on projects in the field of cancer, just to name some of them: H2020-NoCanTher: magnetic nanoparticles against pancreatic cancer through the use of hyperthermia combined with conventional treatment. H2020-Target-4-Cancer: nanotherapy based on polymeric micelles directed against specific receptors of tumor stem cells in colorectal cancer. H2020-DiamStar: nanodiamonds directed against leukemia for the potentiation of chemotherapy. FET-OPEN EvoNano: in silico and tumor-tumor models for the prediction of PK / PD and tumor efficacy of antitumor nanomedicines against tumor stem cells. FIS-ISCIII: polymeric micelles for siRNA and combined therapy against breast cancer tumor stem cells. CarboXigel: hydrogels for the sustained release of chemotherapeutic drugs against the metastatic spread of ovarian cancer. MelanoMir: nanomedicine applied to skin cancer, melanoma, beside other projects promoted by CIBER-BBN.

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Lysosomal Rare Disorders: Focus on Fabry Disease

Last November 19, Vall d’Hebron held a seminar  on Lysosomal Rare Disorders: Focus on Fabry Disease as  part of the Rare Diseases Program at the Vall d’Hebron Campus, in collaboration with the European Commission, the Center for Biomedical Research Network on Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN) and the CIBBIM-Nanomedicine at Vall d Hebron Research Institute (VHIR) through the Smart-4-Fabry projec

In the  second plenary session, moderated by Nora Ventosa and Simó Schwartz, Scientific Directors of NANBIOSIS units 6 and 20 and devoted to New therapeutic strategies for lysosomal disorders, the speakers presented their findings regarding biomarkers, genetic variants and treatment protocols. Ibane Abasolo, Scientific Coordinator of NANBIOSIS Unit 20 gave a talk on Nanomedicine in lysosomal disorders. Project Smart4Fabry .

The Smart4Fabry project, coordinated by CIBER-BBN and with the participation of NANBIOSIS units U3 Synthesis of Peptides Unit, U6 Biomaterial Processing and Nanostructuring Unit and U20 Functional Validation & Preclinical Research (FVPR), was described in the course of this specific day on lysosomal diseases and Fabry’s disease.

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Update and improvement of unit 20 of NANBIOSIS

NANBIOSIS, U20. In Vivo Experimental Platform, led by Dr. Simó Schwartz and Dr. Ibane Ibasolo, has been recently updated and improved as a result of its participation in the project FICTS1420-20, selected by the MICINN for co-financing by the FEDER Program in ICTS 2014-2020. 

These update and improvement include: DLS meassurement system, a fluorimeter and a waterbath for specific activity assays. The fine characterization of the size and size distribution of nanoparticles is essential for the right understanding of their in vivo behavior. The incorporation of this service to the U20 allows the determination of the drug/fluorophore loading/activity of the drug delivery systemistered in vivo, a good quality control of compounds and nanoparticles, as well as the study of their stability upon storage.

 

 

European Regional Development Fund

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Biodistribution, safety and efficacy studies of pharmacological release nanotechnological systems

Ibane Abásolo, Scientific Coordinator of NANBIOSIS U20, explains in this video the studies of biodistribution, safety and efficacy of nanotechnological systems of pharmacological liberation that are developed in this unit and , overall, their expertise and differentiation in the sector in the evaluation of nanosystems (with certification ISO 901-2015)

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