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News U20

News U20

1st Nanomedicine Forum of CIBER-BBN/NANBIOSIS and CSIC Nanomed Conection

During the days 30 of June and 1st of July took place in Barcelona, in the auditorium of the Institute of Advanced Chemistry of Catalonia (IQAC-CSIC), the 1st Forum on Nanomedicine gathering scientists from the CSIC net Nanomed Conection and from the CIBER-BBN and its ICTS NANBIOSIS.

This forum brought toguether researchers from the most eminent national research centers in nanomedicine, that during the two days meeting presented their works and findings and discussed the impact of nanomedicine in the fields of drug delivery, diagnosis and therapy.

The workshop was open by the Director of IQAC-CSIC,  Jesús Joglar, the  Scientific Coordinator of Nanomed Conection, Fernando Herranz, and the Scientific Director of CIBER-BBN, Ramón Martínez Máñez.

18 research groups gave their talks distributed in four sessions:

  • Nanobiotechnological solutions for diagnosis and therapy
  • Drug delivery nanosystems
  • Applications for oncology 
  • Nanomedicine & other frontier applications

The presentations aroused great interest and futher debate among the attendees present in the auditorium (around 50) and the on line participants (The event was also broadcast online previous registration with more than 125 registrations received).

The videos of the presentations will be soon available in the NANBIOSIS youtube channel.

Here we highlight the eight talks by researchers from NANBIOSIS units:

The first session of Nanobiotechnological solutions for diagnosis and therapy,  started  with the talk by Montserrat Rodríguez from Nb4D group NANBIOSIS U2 CAbS, from CIBER-BBN and IQAC-CSIC, entitled “Targeting aromatic amino acid metabolism for the early diagnosis of neurological diseases”, presenting their results on in vitro samples, on thermal power characterization experiments to study the thermal efficiency of non-sinusoidal stimulation and on efficiency characterization experiments in cell cultures with cancer cell liness.

Also in this session chaired by Miriam Royo, Scientific Coordinator of NANBIOSIS U3 Synthesis of Peptides Unit of  CIBER-BBN and IQAC-CSIC,  took place an interesting and passionate talk by Ramón Eritja, Scientific Director of NANBIOSIS U29 Oligonucleotide Synthesis Platform (OSP)

In the last years, interest in therapeutic applications of oligonucleotides has increased enormously, especially after the development of messenger RNA vaccines in response to the COVID-19 pandemic. In this way, metabolic diseases such as dyslipidemia and hereditary diseases such as Duchenne muscular dystrophy have been successfully addressed. The NANBIOSIS  Oligonucleotide Synthesis Platform (OSP) focuses on the design, synthesis and characterization of modified oligonucleotides, in order to enhance the therapeutic properties of the oligonucleotides and to improve the control of gene expression. Ramon Eritja presented their most recent results in the development of new conjugates with antiproliferative activity and in the design of DNA probes for the detection of viral genomes.

 

In the session of “Nanomedicine and other frontiers applications”, chaired by María del Puerto Morales Herrero (ICMM-CSIC), Elena Martínez Fraiz,  from the Nanobioengineering group of CIBER-BBN and IBEC running NANBIOSIS Unit 7 of Nanotechnology, presented  a nanostructured surface able to produce multivalent effects of surface-bound ephrinB1 ligands on the dynamics of oligomerization of EphB2 receptors  whic can benefit applications such as the design of new bioactive materials and drug-delivery systems.

The session of Drug delivery nanosystems, chaired by Ramón Martínez Máñez, began with the talk by Vanessa Díaz Riascos, presesnting the in vivo efficacy, biodistribution and toxicity testing of nanomedicines at NANBIOSIS U20 FVPR, of CIBER-BBN and VHIR, explaining how their texting expertise and their in vivo and ex vivo fluorescence imaging techniques facilitate a rapid and efficient preclinical development of candidates, reducing considerably the time and costs of conventional developments.


Santiago Grijalvo Torrijo, from NANBIOSIS U12 Nanostructured liquid characterization unit expoke about Nano-emulsion-derived polymeric carriers for biomedical applications also discussing the impact of the protein corona on colloidal stability, antioxidant activities, cytotoxicity and cellular uptake of drug-loaded nanoparticles.

Antoni Llopis Lorente, (NANBIOSIS U26 NMR: Biomedical Applications II), expoke about Gated silica nanoparticles for controlled release. Chemical communication, based on the exchange of molecules as messengers, allows different entities to share information, cooperate and orchestrate collective behaviors. Communication using chemical messengers (such as neurotransmitters, hormones and pheromones) is the main way of communication across the natural world; yet engineering chemical communication between micro/nanosystems is a key emergent topic in micro/nanotechnology, biomimicry and related areas. Santiago explainined recent progress by their group in the development of engineered particles for chemical communication and nanomedicine applications.

And closing the session, Mariana Köber (Nanomol Group –NANBIOSIS U6 of Biomaterial Processing and Nanostructuring Unit  from CIBER-BBN and ICMAB-CSIC) gave a talk on Quatsomes as versatile nanovesicles for biomedical applications.

In the session of Applications for Oncology, Pilar Martín Duque from NFP group – NANBIOSIS U9 Synthesis of Nanoparticles Unit of CIBER-BBN and INMA-CSIC, gave a very interesting talk explained their approach and recent progress on the search of trojan horses for an improved theragnosis of cancer.

Here we want to thank the Institute of Advanced Chemistry of Catalonia (IQAC-CSIC) for hosting this event and for the help in its preparation and development.

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Targeting of the breast cancer stem cells to improve the treatment of triple negative breast cancer

On April 1st PhD candidate Patricia Cámara Sánchez defended her doctoral thesis entitled “Targeting of the breast cancer stem cells to improve the treatment of triple negative breast cancer“, where ICTS-Nanbiosis Unit 20 participated in the in vivo assays. The thesis was supervised by Dr. Ibane Abasolo  (scientific director of Unit 20 from CIBER-BBN and VHIR). Nanbiosis was also present within the jury, with Dr. Ana Paula Candiota (scientific coordinator of Unit 25 from CIBER-BBN and UAB) acting as secretary.

Patricia Cámara graduated as biochemist, did the master’s degree in Translational Biomedical Research from VHIR-UAB. Shortly after, started the PhD, which was aimed at improving the treatment of very deadly subtype of breast cancer by using different nanoformulations to specifically target the cancer stem cells. The now doctor Cámara-Sánchez screened up to 20 small drugs with anti-cancer stem cell activity, found synergistic ratios with conventional chemotherapeutic agents, and finally developed polymeric micelles encapsulating selected drugs. During the discussion of the dissertation, the need of additional in vivo assays was highlighted, as well as the potential use of MR provided by the U25, to explore non-invasively the metabolomic differences between cancer stem cells and regular cancer cells.

‘I’m very grateful for the opportunity to have been part of this amazing project. It has been a very enriching experience’, she explains. ‘After 5 years of research, I finish the PhD feeling very proud of having contributed to the fight against this aggressive subtype of breast cancer’, she adds. From now on, new research lines will bring forward the synergies between both units of NANBIOSIS, reinforcing a collaboration started several years ago and reflected in joint papers.

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New equipment installed in NANBIOSIS U20

NANBIOSIS, U20. In Vivo Experimental Platform, led by Dr. Ibane Ibasolo, has been 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 (Equipment for setting standardized immunotoxicology assays for the U20 -NANBIOSIS I17 Action of the Investment Plan-)

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The efficacy of nanoparticles combined with chemotherapy against pancreatic cancer

Pancreatic ductal adenocarcinoma is a highly devastating orphan disease with poor prognosis even when diagnosed early (The survival rate after 5 years (< 5%) has not changed over the last 30 years, despite tremendous research efforts) The european project NoCanTher, in wich participates NANBIOSIS U20 of (VHIR and CIBER-BBN) is a nanotechnology-based approach aimed to scale-up under GMP conditions and evaluate a nanoformulation for a combined therapy with chemotherapy against this pancreatic cancer.

The international clinical study, carried out in the framework of the project is now incorporating the first pacient in Spain with this type of nanotherapy.

The clinical study is based on the results obtained in the preclinical phase of the NoCanTher project, with the group of the CIBBIM (of CIBER-BBN and VHIR, led by Dr. Ibane Abasolo). This new technology based on magnetic nanoparticles increases the accessibility of chemotherapy to pancreatic tumors. Researchers have developed magnetic iron nanoparticles that, under an alternating magnetic field, generate heat – magnetic hyperthermia. This heat is able to be used because the tumor cells are still more sensitive to the standard treatment with chemotherapy and, therefore, in greater efficiency, and ultimately it is possible to directly destroy these cells.

As explained by Dra. Ibane Abasolo, Scientific Director of Nanbiosis unit 20 of CIBER-BBN and VHIR: NANBIOSIS has played an important role in this project in relation with the preclinical in vivo trials in animal models (mice). We made human pancreatic cancer cells grow and studied the efficacy of nanoparticles and their combination with chemotherapy. Specifically, we saw that i) tumor heating by magnetic hyperthermia slowed down tumor growth, but that it was necessary to combine this treatment with conventional chemotherapy to have a better effect, that ii) the hyperthermia-chemotherapy sequence that worked best (it is better to warm up first and treat with chemotherapy later than to put chemotherapy first) and iii) that the combination of hyperthermia/chemotherapy was beneficial because it greatly reduces the stroma of the tumor and makes it easier for chemotherapy to reach tumor.


The NoCanTher project is coordinated by IMDEA Nanociencia (Madrid) and includes the participation of eleven national and international centers: BioKeralty Research Institute (Miñano), ImmuPharma (London), Chemicell (Berlin), University Hospital (Jena, Germany), Resonant Circuits (London), Vall d’Hebron Research Institute (VHIR) (Barcelona), Vall d’Hebron Institut d’Oncology (VHIO) (Barcelona), Trinity College (Dublin), Paris Diderot University (Paris), Hospital Universitari of Fuenlabrada (Madrid). The initiative is funded by Horizon 2020 (GA:685795).

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Open Call Focus on Innovative MedTech using Nanotechnology

Start-ups / SMEs! Are you working on innovative medical products using nanotechnology? This is your call for development and marketing solutions!

Last week took place the SAFE-N-MEDTECH Open Call on line info session with the idea to present the open call with a bit more detail. A few presentations and specially a time for questions and answers were organized by Anaïs Le Corber, Network Manager of CEBERG, the council of European Bioregions, partner of the project.

The webinar was recorded and it is available here:

First of all, Angel del Pozo, Coordinator of the SAFE-N-MEDTECH, gave an insight of the project.

Then, Miguel Duarte from IMM (Portugal), the business development partner of the project, presented the services offered

After him, Qwentin Pankhurst, chairman of Resonant Circuits Ltd. explained his experience as user, having a tase case in the project.

Finaly, before the space for questions and answers, Ibane Abasolo, Scientific Director of NANBIOSIS U20, from CIBER-BBN and Vall D’Hebron Institute Research in Barcelona, presented with more detail the clinical validation services available in this open call.

SAFE-N-MEDTECH OITB  Safety testing in the life cycle of nanotechnology-enabled medical technologies for health is a H2020 project with the objective of providing services and support to companies and other organizations for accelerating the development and commercialization of innovative MedTech solutions based on nano-enabled technology.

How can this call suit you?

Qwentin Pankhurst explained his experience: “As a medtech start-up we do not have the external experience to cover all the safety related aspects of product development for MDR compliance, we needed clear uncomplicated advance and solutions, ideally we needed a “one-stop-shop”…

“Even if a client accesses only a part of the offering, the fact that the OITB is seeking to cover the entire pathway from design input to clinical testing is important as it underpins a connected-thinking approach.”

Submission deadline: March 21st 2022, 23:59 CET

The time line: It is espected that the evaluation process will take around one month. Then NDAs will be signed before starting the work, which could be carried during one year approximatly.

The technology assesment area of the SAFE-N-MEDTECH OITB well carry out a first examitanion toguether with the applicant of the available data, the quality of the data, the needs of the product an other relevant aspects. A technology assitant proposal will ve developed and the services needed will be defined toguether with the client.

Call documents:

  • Guidelines for Applicants The Guide for Applicants contains the basic information needed to guide you in preparing a proposalfor submission to the SAFE-N-MEDTECH Open Call. It gives an introduction on how to structureyour proposal. It also describes how to submit the proposal and the evaluation criteria.
  • Application Form

This call uses funds obtained within the scope of the SAFE-N-MEDTECH project funded by European Union´s Horizon 2020 Research and Innovation Program. (Grant Agreement No. 814607)

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Fabry Desease in the Rare Disease Day: A New Hope

WHY DO CELEBRATE TODAY THE INTERNATIONAL #RareDiseaseDay?

29 of February is a ‘rare’ date and February, a month with a ‘rare’ number of days, has become a month to raise awareness about rare diseases and their impact on patients’ lives.  Since 2008 thousands of events happen every year all around the world and around the last day of February with the aim of improving equity and reducing stigmatization for people who live with more than 6,000 rare diseases.

WHAT ARE RARE DISEASES

Rare diseases are pathologies or disorders that affect a small part of the population (less than 5 per 10,000 inhabitants) and generally have a genetic component. They are also known as orphan diseases.

Diseases present a series of particular symptoms, and it is very difficult to diagnose what their true cause is. These disorders or alterations that patients present must be evaluated by a specialist, depending on each case.

Today 5% of the world population suffer from them. This translated into numbers, corresponds to approximately 300 million affected.

A patient with a rare disease waits an average of 4 years to obtain a diagnosis, in 20% of cases it takes 10 or more years to achieve the proper diagnosis.

ORPHAN DRUGS

To combat this disease, patients need to be treated with so-called orphan drugs. They serve to prevent and treat pathology. Its composition is based on biotechnological compounds whose manufacture is very expensive and not profitable for companies. For this reason, cooperation of governments is needed as well as financial incentives to encourage pharmaceutical companies to develop and market medicines to make these treatments accessible to a greater number of people.

FABRY DISEASE

Fabry is one of the rare diseases that currently lack a definitive cure. Symptoms may include episodes of pain, especially in the hands and feet (acroparesthesias); small dark red spots on the skin called angiokeratomas; decreased secretion of sweat (hypohidrosis); opacity of the cornea (cataracts) and hearing loss. Internal organs such as the kidney, heart, or brain may be involved, resulting in progressive kidney damage, heart attacks, and strokes.

Fabry disease is a lysosomal storage disease arising from a deficiency of the enzyme α-galactosidase A (GLA). The enzyme deficiency results in an accumulation of glycolipids, which over time, leads to cardiovascular, cerebrovascular, and renal disease, ultimately leading to death in the fourth or fifth decade of life. Currently, lysosomal storage disorders are treated by enzyme replacement therapy (ERT) through the direct administration of the missing enzyme to the patients.

SMART 4 FABRY” EUROPEAN PROJECT

CIBER-BBN, through the researcher Nora Ventosa has coordinated the european project “Smart-4-Fabry” developed during 2017-2021, the proyect was undertaken by a consortium formed by ten partners, including private companies and public institutions in Europe and Israel, with a Horizon 2020 financial programme by the European Commission (H2020-NMBP-2016-2017; call for nanotechnologies, advanced materials, biotechnology and production; Proposal number: 720942-2).

In view of their advantages as drug delivery systems, liposomes are increasingly being researched and utilized in the pharmaceutical, food and cosmetic industries, but one of the main barriers to market is their scalability.

Depressurization of an Expanded Liquid Organic Solution into aqueous solution (DELOS-susp) is a compressed fluid-based method that allows the reproducible and scalable production of nanovesicular systems with remarkable physicochemical characteristics, in terms of homogeneity, morphology, and particle size. The objective of this work was to optimize and reach a suitable formulation for in vivo preclinical studies by implementing a Quality by Design (QbD) approach, a methodology recommended by the FDA and the EMA to develop robust drug manufacturing and control methods, to the preparation of α-galactosidase-loaded nanoliposomes (nanoGLA) for the treatment of Fabry disease.

Through a risk analysis and a Design of Experiments (DoE), researechers obtained the Design Space in which GLA concentration and lipid concentration were found as critical parameters for achieving a stable nanoformulation. This Design Space allowed the optimization of the process to produce a nanoformulation suitable for in vivo preclinical testing.

The new nanoformulation developed by Smart4Fabry for the treatment of Fabry disease achieved the ODD (Orphan Drug Designation) by the European Commission. The new nanomedicine is more effective and has a better biodistribution than the current treatments, based on enzyme replacement. The new nanomedicine is based on a nanovesicle that protects the enzyme and achieves a better cell internalisation, thus reducing the doses needed, the total cost and improving the quality of patients.

Four units of NANBIOSIS participated in the project:

– U1 Protein Production Platform (PPP) led by Neus Ferrer and Antony Villaverde at IBB-UAB for the production and purification in different expression systems for R&D purposes.

– U3 Synthesis of Peptides Unit led by Miriam Royo at IQAC-CSIC performed all the chemical process of the Smart-4-Fabry project, i.e. design and synthesis of peptides used as targeting ligands in the nanoliposome formulation.

– U6 Biomaterial Processing and Nanostructuring Unit led by Nora Ventosa at ICMAB-CSIC developed tasks related to the manufacture of the nanoliposome formulation of GLA enzyme and the physico-chemical characterization (this unit counts with plants at different scales, from mL to L, which allow process development by QbD and process scale-up, as well as instrumental techniques for assessment of particle size distribution, particle concentration, particle morphology and stability, and Z-potential) .

– U20 In Vivo Experimental Platform led by Ibane Abásolo at VHIR carried out the non-GLP preclinical assays of the project (in vivo efficacy, biodistribution and tolerance/toxicity assays).

PHOENIX: OPEN INNOVATION TEST BED

Researchers of CIBER-BBN and NANBIOSIS, led by Nora Ventosa, are currently participating in another european project, PHOENIX “Enabling Nano-pharmaceutical Innovative Products” in the framework of which this novel nanomedicine developed under the Smar4Fabry project and designed as Orphan Drug by the EMA, will be scaled-up and manufactured under GMP to enable its clinical testing.

Articles of reference:

Josep Merlo-Mas, Judit Tomsen-Melero, José-Luis Corchero, Elisabet González-Mira, Albert Font, Jannik N. Pedersen, Natalia García-Aranda, Edgar Cristóbal-Lecina, Marta Alcaina-Hernando, Rosa Mendoza, Elena Garcia-Fruitós, Teresa Lizarraga, Susanne Resch, Christa Schimpel, Andreas Falk, Daniel Pulido, Miriam Royo, Simó Schwartz, Ibane Abasolo, Jan Skov Pedersen, Dganit Danino, Andreu Soldevila, Jaume Veciana, Santi Sala, Nora Ventosa, Alba Córdoba, “Application of Quality by Design to the robust preparation of a liposomal GLA formulation by DELOS-susp method”, The Journal of Supercritical Fluids, Volume 173, 2021, 105204, https://doi.org/10.1016/j.supflu.2021.105204.

Judit Tomsen-Melero, Solène Passemard, Natalia García-Aranda, Zamira Vanessa Díaz-Riascos, Ramon González-Rioja, Jannik Nedergaard Pedersen, Jeppe Lyngsø, Josep Merlo-Mas, Edgar Cristóbal-Lecina, José Luis Corchero, Daniel Pulido, Patricia Cámara-Sánchez, Irina Portnaya, Inbal Ionita, Simó Schwartz, Jaume Veciana, Santi Sala, Miriam Royo, Alba Córdoba, Dganit Danino, Jan Skov Pedersen, Elisabet González-Mira, Ibane Abasolo, and Nora Ventosa. Impact of Chemical Composition on the Nanostructure and Biological Activity of α-Galactosidase-Loaded Nanovesicles for Fabry Disease Treatment, ACS Appl. Mater. Interfaces 2021, 13, 7, 7825–7838 ( https://doi.org/10.1021/acsami.0c16871).

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Women in the fight against breast cancer: Ibane Ibasolo

The International Day of Women and Girls in Science on February 11 honor women’s significant achievements in science and place a much-needed focus on girls entering Science, Technology, Engineering, and Mathematics (STEM) careers.

We want to take this day to congratulate all the women scientists, especially our scientists at NANBIOSIS ICTS. Some of them take an active role in the dissemination of research results and reseach contribution to the society, as Dr. Ibane Abasolo who last week participated in different events to explain her team work in the figth against breast cancer.

Ibane Abasolo is the Scientific Coordinator of NANBIOSIS U20 and also the leader of the Drug Delivery & Targeting group of the CIBER-BBN at the Vall d’Hebron Research Institute (VHIR) which coordinates the unit 20 of NANBIOSIS, a team composed mainly by women.

The group cooworks to improve cancer treatment through the development of nanoparticles specially directed towards breast cancer stem cells. These cells are the ones that, despite dividing slowly, give rise to the differentiation of the rest of the tumor cells and are also the most resistant to conventional antitumor treatments.

That is why the group seeks to attack these cells in three ways:

i) selected drugs that induce the differentiation of tumor stem cells into more differentiated cells (and easier to treat),

2) using mechanisms to evade the efflux pumps of drugs and

3) targeting the nanoparticles specifically towards tumor stem cells by using targeting agents (ie antibodies) against antigens on the surface of tumor stem cells.

Dr. Abasolo has illustrated these three approaches by citing papers published in her group during 2021, in which the ICTS Nanbiosis U20 has also directly participated:

Gustavo Carreño, Alfredo Pereira, Fabián Ávila-Salas, Adolfo Marican, Fernanda Andrade, Maria Mercé Roca-Melendres, Oscar Valdés, Sekar Vijayakumar, Simó Schwartz, Ibane Abasolo, Diana Rafael, Esteban F. Durán-Lara, Development of “on-demand” thermo-responsive hydrogels for anti-cancer drugs sustained release: Rational design, in silico prediction and in vitro validation in colon cancer models, Materials Science and Engineering: C, Volume 131, 2021, 112483, ISSN 0928-4931, https://doi.org/10.1016/j.msec.2021.112483.

Yolanda Fernández, Julie Movellan,Laia Foradada, Vanessa Giménez, Natalia García-Aranda, Sandra Mancilla, Ana Armiñán, Sven Even Borgos, Astrid Hyldbakk, Anna Bogdanska, Oliviero L. Gobbo, Adriele Prina-Mello, Jessica Ponti, Luigi Calzolai, Oleksandr Zagorodko, Elena Gallon, Amaya Niño-Pariente, Alison Paul, Simó Schwartz Jr, Ibane Abasolo, María J. Vicent In Vivo Antitumor and Antimetastatic Efficacy of a Polyacetal-Based Paclitaxel Conjugate for Prostate Cancer Therapy. Adv Healthc Mater. 2021 Oct 27;e2101544. doi: 10.1002/adhm.202101544.

Diana Rafael, Maria Mercè Roca Melendres, Fernanda Andrade, Sara Montero, Francesc Martinez-Trucharte, Mireia Vilar-Hernandez, Esteban Francisco Durán-Lara, Simó Schwartz Jr, Ibane Abasolo,
Thermo-responsive hydrogels for cancer local therapy: Challenges and state-of-art, International Journal of Pharmaceutics, Volume 606, 2021,
120954, ISSN 0378-5173, https://doi.org/10.1016/j.ijpharm.2021.120954.

Marwa M Abu-Serie , Fernanda Andrade, Patricia Cámara-Sánchez, Joaquin Seras-Franzoso, Diana Rafael, Zamira V Díaz-Riascos, Petra Gener, Ibane Abasolo, Simó Schwartz Jr Pluronic F127 micelles improve the stability and enhance the anticancer stem cell efficacy of citral in breast cancer. Nanomedicine VOL. 16, NO. 17. 2021 Jul;16(17):1471-1485. doi: 10.2217/nnm-2021-0013.

Eva Espinosa-Cano, Miguel Huerta-Madroñal, Patricia Cámara-Sánchez, Joaquin Seras-Franzoso, Simo Schwartz, Ibane Abasolo, Julio San Román, Maria Rosa Aguilar, Hyaluronic acid (HA)-coated naproxen-nanoparticles selectively target breast cancer stem cells through COX-independent pathways, Materials Science and Engineering: C, Volume 124, 2021, 112024, ISSN 0928-4931, https://doi.org/10.1016/j.msec.2021.112024.

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, Ibane Abasolo, Bruno Sarmento, Simó Schwartz, Polymeric 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, 2021, 198-212, ISSN 0168-3659, https://doi.org/10.1016/j.jconrel.2021.01.022.

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Multivalent self-assembled platforms for the delivery of chemotherapeutic drugs

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.

Dr. Miriam Royo, who leads NANBIOSIS unit 3 of Synthesis of Peptide, explains one of the projects in which the ICTS is involved in relation with cancer therapy.

The improvement of solubility and stability of clinically approved chemotherapeutic drugs still represent a big challenge in cancer therapy. In fact, many of these drugs have low water solubility, which forces to administer larger volume doses to achieve the desired biological effect, and increases the side effects suffered from patients. The active principle can be chemically modified to increase the solubility, and administered as prodrug which, however, has to be enzymatically metabolized to have therapeutic effect and only a low percentage of the free drug is achieved. Moreover, some of the chemotherapeutic drugs are unstable at physiological conditions due to their chemical structure, and rapidly degrades before reaching the tumor tissue, further reducing the effectiveness of the treatment. Drugs commonly used in clinical chemotherapy treatments for advanced colorectal cancer and triple negative breast cancer, such as SN38, 5-fluorouracil (5-FU) and paclitaxel (PTX), have presented these problems, which affect their efficacy and tolerance to treatment by patients.

Drug delivery nanosystems based on biocompatible polyethylene glycol (PEG)-based multivalent platforms conjugated to hydrophobic drugs (SN38, PTX among others) are developed by the Multivalent Systems for Nanomedicine (MS4N) goup of Centro de Investigación Biom´dcia en Red (CIBER-BBN) at the Institute for Advanced Chemistry of Catalonia (IQAC-CSIC). The resulting water-soluble conjugates have also the ability to self-assemble in aqueous media in nanoscale micellar structures improving the pharmacokinetic profile of drugs. In these systems, the intact active principle can be released in a controlled manner thanks to the presence of degradable bonds, between the drug and the polymer, which are sensitive to chemical or biological stimuli, favoring its accumulation in tumor.

Systems containing only one drug (SN38 or PTX) for monotherapy and two different drugs (as SN38 and 5-FU) for combined therapy treatments are developed to improve the therapeutic efficacy of the free drugs and decrease their secondary effects.  The multivalence nature of these systems also allows the possibility to add targeting agents, such as tumor specific peptide ligands thus increasing the specificity of the platforms towards the cancer cells. These peptide ligands have been produced at the Synthesis of Peptides Unit (U3) of NANBIOSIS.

This project (RTI2018-093831-B-I00) is funded by MICIN/AEI/10.13039/501100011033 and by “ERDF A way to of making Europe and performed in collaboration with Dr. Ibane Abasolo group of CIBER-BBN at Vall d’Hebron Research Institute (VHIR) and the In Vivo Experimental Platform (U20) of NANBIOSIS under the frame of CIBER BBN intramural collaborative projects (PolyPlaTher, Colocomb and Nanomets).

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New therapeutic strategies for the treatment of advanced breast and colon cancer

Sara Montero, researcher of the “Drug Delivery and Targeting” of CIBER-BBN and VHIR, presented her thesis work on November 22 “Nanotecnnology mediated extrategies targeting cancer stem cells for advanced cancer tratment”, directed by Dr. Simó Schwrtz and Dr Diana Rafael.

In vivo experiments where carried out through the Unit 20 of the ICTS NANBIOSIS.

The work presented by Sara Montero shows two different types of therapeutic strategies for the treatment of advanced breast and colon cancer. Both strategies focus on blocking proteins essential for the survival and proliferation of cancer stem cells (CMC), known to be the main responsible for current therapeutic failures, tumor repopulation after treatments, as well as the causes of the aggressiveness of the resulting metastases. In addition, both strategies take advantage of the advantages offered by nano-drug delivery systems (nano-DDS) to increase the therapeutic efficacy of administered anticancer agents, reduce harmful side effects and, most relevant, specifically eliminating the CMC fraction within tumors. This project has also made it possible to evaluate the effects of combined therapy, using conventional drugs for the treatment of the disease together with specific molecules for the eradication of CMC in the same nanoplatform; specifically a system of polymeric micelles made up of the amphiphilic polymer Pluronic® F127. Together, this work opens the possibility of co-administering different types of compounds to simultaneously eliminate the two main cell populations that make up tumors and thus achieve complete tumor remission.

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Extracellular vesicles secreted by cancer stem cells promote angiogenesis and disease progression

Patricia González, researcher of the “Drug Delivery and Targeting” of CIBER-BBN and VHIR, presented her thesis work on November 19 where she lays the foundations to understand the role of different subpopulations of extracellular vesicles (VEs) secreted by tumor models in the regulation of tumor plasticity, as well as its effect on the tumor microenvironment and disease progression.

In the project, it has been described for the first time how the VEs secreted by the cancer stem cell subpopulation are responsible for activating fibroblasts in the tumor microenvironment and promoting angiogenesis, thus facilitating disease progression. Furthermore, it has been possible to discern the role of these vesicles in the regulation of cell plasticity. In this sense, the VEs from tumor stem cells would act as effectors of cell differentiation in contrast to the action of the VEs secreted by differentiated cancer cells, which would stimulate the acquisition of stem cell characteristics.

In order to carry out the in vivo experiments, the services of ICTS Nanbiosis were used, through the U20.

The results open a new line of research in the group with a long journey ahead, setting as main objectives the identification of the molecular actors responsible for the activities described above as well as the translation of said knowledge into specific therapeutic strategies.

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