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Nanoparticles to modulate topography and ligand distribution at the nanoscale: impact on cell behavior

Doctor Marc Martínez from the Nanomol-Bio group – NANBIOSIS U6 from CIBER-BBN at ICMAB-CSIC, defended his PhD thesis “Nanoparticles to modulate topography and ligand distribution at the nanoscale: impact on cell behavior” on 9 March 2023 at ICMAB.

he PhD thesis was supervised by Imma Ratera, Judith Guasch and Nora Ventosa from the Nanomol-Bio group at ICMAB-CSIC.

Ana Paula Candiota Silveira, Scientific Coordinator of NANBIOSIS U25 was part of the Committee that evaluated the Thesis tooghether with Jesús Martínez de la Fuente, Instituto de Nanociencia y Materiales de Aragón (INMA-CSIC) (President),  and Anna Lagunas Targarona, Institut de Bioenginyeria de Catalunya (IBEC) (Vocal).

As Marc Martínez explained in an inteview to ICMAB “I produce nanoparticles in the lab and I use them to see how cells react to them. I work at the interface between cells and materials. My research can be applied to cell culture, which can be relevant for the development of new therapies for the regeneration of organs or for building implants to replace missing organs and body parts”.

Doctor Marc Martínez’s PhD thesis was part of the PhD Programme in Biochemistry, Molecular Biology and Biomedicine from the Universitat Autònoma de Barcelona (UAB).

Further information at ICMAB webpage

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Wide representation of NANBIOSIS research in NALS 2022 and best Oral Presentation to Eloi Parladé

During the last 27-29 April, the 3rd International Conference on Nanomaterials Applied to Life Sciences 2022 (NALS 2022) has taken place in the Excellence Campus of Universidad de Cantabria in Santander (Spain), organized by the University of Cantabria and Institute Valdecilla-IDIVAL.

NALS 2022 has been a multidisciplinary conference series sharing new results and ideas in the fields of biosensors, lab on a chip, drug delivery nanopharmacy. nanobiotechnology, intelligent nanomaterials, magnetic materials, nanotoxicity, antimicrobials, novel applications of 3d bioprinting and nanoimaging.

NANBIOSIS has been represented at this edition by members of several of its units, among them we must highlight the set of four oral communication presented by members of the Nanobiotechnology group-Unit 1 of NANBIOSIS “Protein Production Platform (PPP)”, from CIBER-BBN and IIB-UAB the talks were delivered by:

Eloi Parladé: “Development of ion-dependent microscale secretory granules for nanomedical applications”

Carlos Martínez-Torró: “Design of a human GFP-like protein scaffold for targeted nanomedicines”

Eric Voltá Durán: “Antitumoral nanoparticles with multiple activities, a close reality”

Jan Atienza-Garriga: “Characterization of protein-only NPs containing amps and analysis of their protection with liposomes and micelles”

They summarized a wide area of the team activities on the design of protein-based protein materials for clinical uses, produced by means of diverse types of cell factories. In particular, antimicrobial peptides, cytotoxic proteins with antitumoral targeting and drug-carrying scaffold proteins are engineered to confer self-assembling properties as either microparticles or nanoparticles, that can be further functionalized with chemical drugs through covalent binding. Microparticles are of special interest as they can be used as slow drug delivery systems for nanostructured drugs upon subcutaneous administration. Alternatively, nanoparticles can be also presented as embedded in liposomes or other micellar structures that stabilize them for enhanced performance.

Three NANBIOSIS units supported the presented research, which has been executed in a highly cooperative way: namely U1 (Protein Production Platform), led by Tony Villaverde U18 (Nanotoxicology), led by Ramón Mangues and U29 (Oligonucleotide Synthesis Platform), led by Ramón Eritja.

Among all the excellent contributions by the team, it is worthy to stress that the prize for the best Oral Presentation was granted to Dr Eloi Parladé.

Other talk by researchers from NANBIOSIS were “Antioxidant-loaded polymeric NPs prepared by nano-emulsion templating for the management of neurological diseases” by Santiago Grijalvo, from NANBIOSIS U12 and  “Exploiting GSH oxidation with nanocatalysts to promote cancer cell death” by Javier Bonet-Aletá from NANBIOSIS U9

On the other hand, Jesús Santamaría,  Scientific Director of NANBIOSIS U9 was a Keynote Speaker in the Conference with the talk: “A change of paradigm in cancer therapy? Using catalysts to make drugs inside the tumor, rather than trying systemic chemotherapy”

NALS 2022 has been an excellent conference, with presentations covering a wide range of topics in nanomaterials for health, and a great opportunity for our researchers, especially for young’s, to let know their collaborative work, as well as make new connections on common research interests, thanks to the good socializing opportunities afforded by the scheduling of the organization conference.

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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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New project ExofluidTT for the production of nanovesicles using microfluidics applicable on Biomedicine

Víctor Sebastián Cabeza, researcher of NANBIOSIS U9 Synthesis of Nanoparticles of CIBER-BBN and the Institute of Nanoscience and Materials of Aragón, INMA, has obtained a research grant in the XX National Contest of the Ramón Areces Foundation in the category of Life and Matter Sciences with a funding of € 112,000 for the development in 3 years of nanovesicles using microfluidic technology.

As explained by Victor Sebastian “the characterization of the nanovesicles will be carried with the equiment and expertise of NANBIOSIS Unit 9

The project entitled “Engineering of extracellular vesicles-exosomes using microfluidic technology for its application in biomedicine: ExoFluidTT” aims to develop new procedures to improve the selectivity and efficiency of therapeutic treatments, such as, for example, cancer. The nanocarriers considered in ExoFluidTT are called exosomes and are nano-sized extracellular vesicles, produced by the patient’s own cells and whose structure and composition is so complex that their production by synthetic procedures is not possible. The application of these vesicles is creating a revolution in cellular treatments, since they allow to face the problems in which artificial nanocarriers fail. However, its clinical use is complex, due to the difficulty of its production, isolation and reconfiguration for the treatment of diseases.

The ExoFLuidTT project aims to design an innovative platform based on the use of exosomes for its application in targeted therapies. The basis of this innovative platform is based on the use of microfluidic technology to obtain the exosomes of the patient’s cells. These exosomes would be isolated for their reconfiguration aimed at obtaining nanocarriers that allow the administration of drugs in a targeted manner. This microfluidic technology consists of a complex system of pipes and micrometric-scale reactors (similar to the dimensions of a human hair) that mimic the highly efficient network of blood capillaries that the human body has, so that, in an efficient way, they can be manipulate volumes of fluid on the scale of picoliters (one millionth of a drop).

This project is based on the previous experience of Víctor Sebastián Cabeza in the development of microfluidic technology for multiple uses in Catalysis, Materials Engineering and Nanobiomedicine, as well as the experience of his work team, ExoFLuidTT, in the use of exosomes as therapeutic nanocarriers. This team has recently published a study where they were able to successfully develop exosomes modified with palladium nanosheets for the selective activation of prodrugs in-vitro and to treat tumor cells selectively. The results of this work were published in the prestigious journals Nature Catalysis and Nature Protocols and open a therapeutic pathway that can have a great social impact.

The project work team, led by Víctor Sebastián, is made up of CIBER-BBN researchers Manuel Arruebo and Jesús Santamaría, all of them professors from the Department of Chemical Engineering and Environmental Technologies at UNIZAR, and researchers from INMA and IISAragón . Researchers Silvia Irusta (INMA / CiberBBN / IIS Aragón) and Pilar Martín Duque (ARAID / IACS / IISAragón) collaborate with this team.

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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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Novel Quatsome nanovesicles, prepared using compressed CO2, for the development of advanced nanomedicines

Guillem Vargas Nadal, researcher at Nanomol Group – NANBIOSIS U6 (ICMAB-CSIC and CIBER-BBN) and Nanomol Technologies will defend his PhD thesis on Friday, 23 October 2020, at 11 am in an online session. The PhD Thesis Defense will be held by videoconference from the ICMAB Meeting Room. 

Further information and Registration to attend the PhD Thesis defense via Zoom nanoparticles at ICMAB-website.

Supervisors:

  • Nora Ventosa (Scientific Director of NANBIOSIS U6 Biomaterial Processing and Nanostructuring Unit and leader of Nanomol Group of CIBER-BBN
  • Lidia Ferrer (Nanomol Technologies S.L.)

Abstract: The nanovesicles are being developed and investigated to be used in the pharmaceutical world to deliver drug and detect diseases. However, there are some drawbacks related to the nanovesicles that must be considered, like their stability and their applicability. Concerning that, in this Thesis we have developed a new type of stable nanovesicles called MKC-Quatsomes to be used as intravenous drug delivery systems. Their production, physicochemical characteristics, and stability are strongly related to the dispersant medium. Furthermore, the MKC-Quatsomes were labeled with fluorescent organic dyes, which present FRET phenomenon in order to overcome the drawbacks of the single-dye-loaded nanoparticles.


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II Conference on Nanotoxicity, organised by Nanomed Spain, NANBIOSIS and Materplat, Sept. 22

NANBIOSIS is organizing an on-line Conference on Nanotoxicity in collaboration with Nanomed Spain and Materplat, next September 22, to debate about the efect of nanotoxicity of nanoparticles and nanotechnologies in health.

Nanotechnology, a science involved in the design, production, and use of structures and objects that have at least one of their dimensions on the scale of 100 nanometers or less, is enabling progress to be made in various areas with far-reaching repercussions. scope for society. Currently, there are several areas in which nanotechnology is under development or even in the practical application phase.

However, manufactured nanoparticles can have very different properties and effects than those of the same materials in conventional sizes, which can pose new risks to human and other species’ health. Some nanoparticles, which are used as a vehicle for the drugs to reach the desired cells in greater quantity, to reduce the side effects of the drug in other organs or for both, have the same dimensions as certain biological molecules and can interact with them.

The increase in potential health risks has created a new discipline, nanotoxicity, that is, the study of toxicity produced by the effect of nanoparticles and nanomaterials. The objective of this conference, co-organized by the advanced materials and nanomaterials platform (MATERPLAT), NANBIOSIS ICTS and the nanomedicine platform (Nanomed Spain), is to learn more about the lines that are being followed in research in the area of ​​nanotoxicity, the progress of different projects in this field, as well as existing tools to understand and reduce the toxicity of nanoparticles and nanomaterials.

The event will count with the expertise of Marisa Gonzalez, Scientific Director of NANBIOSIS U16 Surface Characterization and Calorimetry Unit, speaking about Surface characterization of micro and nanoplastics among other experts.

The assistance is free but it is necessary to register. For further information, agenda and registration click here 

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

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

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

More information at the ICMAB website.

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A recombinant SARS-CoV-2 vaccine

NANBIOSIS Protein Production Platform (PPP) Unit 1 (of CIBER-BBN and Autonomous University of Barcelona) is involved in a micro-patronage project for the development of a vaccine for COVID 19.

NANBIOSIS Unit 1 is directly involved in the initial part of the Virus Like Particles and Proteins expression and purification project of SARS-COV-2

Most vaccines used today are based on either attenuated forms of the original pathogen, or are inactivated vaccines, in which the pathogen has undergone physical or chemical treatments to eliminate its infectivity. The project proposes to use a new vaccine strategy based on recombinant proteins in imitation of viruses (virus-like particles or VLPs). The same strategy with which, for example, papillomavirus and hepatitis B virus vaccines have been created.

VLPs contain recombinant structural proteins, obtained by the introduction and expression of a gene in cultured cells, that form nanostructures similar to viral particles but do not contain their genetic information and, therefore, are not infectious. These particles are capable of arousing a strong immune response as they form a three-dimensional structure where the virus epitopes are exposed, but they are very safe.

VACCINE PROTOTYPE:

Design
First, we will design the genes that encode the structural proteins of the virus. At this point, the different sequences of the virus genome deposited in public databases must be analyzed and compared in detail. In this way, we can select the most representative sequence. On the other hand, we will carry out some control tests to detect the different fragments of the proteins where the response of the immune system is concentrated, the so-called antigens.
These studies will be carried out using bioinformatics tools by the Computational Biology Group of dr. Xavier Daura from the UAB Institute of Biotechnology and Biomedicine (IBB).

Production and purification
To carry out these productions, we need to use cultured cell lines in which we introduce the genes that encode the virus’s proteins and establish optimal obtaining conditions, without the need to use highly biological containment laboratories. Once produced, we will carry out a purification process and they can be validated.

This block will be carried out in parallel by the research group led by Dr. Francesc Godia from the Department of Chemical, Biological and Environmental Engineering, and Dr. Neus Ferrer from the Department of Genetics and Microbiology and member of the Nanobiotechnology Group led by Dr Antoni Villaverde, attached to the IBB and the CIBER-BBN. In addition, we will have the help of UAB research-scientific-technical services, such as the Microscopy Service (SM), and the Proteomics and Structural Biology Service (sePBioEs) and a unique scientific-technical infrastructure called NANBIOSIS.

Validation with patient serum and cell models
Once the proteins are purified, it is necessary to validate the vaccine formulations with patient serum. In other words, it must be demonstrated that the patient sera of the COVID-19 are linked to the vaccine proposals developed. This task will be coordinated by dr. Eduard José Cunilleras from the UAB Department of Animal Medicine and Surgery in collaboration with doctors from the Parc Taulí, Germans Trias, Vall d’Hebron and Santa Creu i Sant Pau hospitals, and the help of the scientific-technical service to support the research of the Crop, Antibody and Cytometry Service (SCAC) of the UAB.

TESTS ON ANIMALS

Any product to be administered to humans must first go through a preclinical phase in animal models. All trials, when they reach this stage, must be approved by the Ethics Committee on Animal and Human Experimentation. The safety and efficacy of the vaccine are tested in these models.

During vaccination trials we will monitor the weight of the animals and their general condition. The presence of antibodies in the blood of vaccinated animals will be evaluated in cell cultures. The serum of the vaccinated animals will be incubated with the SAR-CoV-2 and we will proceed to the infection of cell cultures. If the antibodies are capable of reducing the infectivity of the virus, then we will move on to the final part of this stage, which will consist of infecting the vaccinated animals with the virus to see if they are protected from infection. A group of unvaccinated animals will also be infected and we will compare the results with another group of unvaccinated and uninfected animals. The vaccine should give similar results to the last group of animals.

Further information about the project and FAQs about donations: https://micromecenatge.uab.cat/vacunacoronavirus

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“Molecular probes and gated materials in biomedical applications and communication between nanoparticles” by Ramón Martínez

Next June 8, 2020, 12 pm, Ramón Martínez Máñez, Scientific Director of CIBER-BBN and NANBIOSIS U26, give an on line seminar, hosted by Jaume Veciana and Anna Roig will from ICMAB-CSIC.

The development of optical molecular probes and probes based on gated nanoparticles has been an area of interest during the last decades. Optical probes are able to transform chemical information in the environment into a suitable optical signal, usually a change in colour of fluorescence. Moreover, gated materials have also been widely used for the development of drug delivery systems.

Some examples of optical probes and gated materials for sensing and controlled delivery in biomedical applications will be described. From another point of view, the talk will also describe how nanoparticles are able to communicate each to another via the exchange of chemical messengers. Communication between nanodevices may find applications in different areas and a number of future new results are envisioned in this research field.

The development of optical molecular probes and probes based on gated nanoparticles has been an area of interest during the last decades. Optical probes are able to transform chemical information in the environment into a suitable optical signal, usually a change in colour of fluorescence. Moreover, gated materials have also been widely used for the development of drug delivery systems.

Register HERE to attend the seminar via Zoom. 

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