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Posts Taged nanoparticles

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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Infrared sensitive hydrogels to control the regeneration of bone tissue.

NANBIOSIS U9 Synthesis of Nanoparticles Unit has participated in a research carried out bu researchers of CIBER-BBN group FIOBI-HULP at Hospital de la Paz, led by Nuria Vilaboa. reclently published in the scientific journal Biomaterials The researchers have used transgenic cells, which are incorporated into the scaffolding, to regulate the physiological production of bone growth factors and induce the osteoinduction process.

Achievement of spatiotemporal control of growth factors production remains a main goal in tissue engineering. In the present work, we combined inducible transgene expression and near infrared (NIR)-responsive hydrogels technologies to develop a therapeutic platform for bone regeneration. A heat-activated and dimerizer-dependent transgene expression system was incorporated into mesenchymal stem cells to conditionally control the production of bone morphogenetic protein 2 (BMP-2). Genetically engineered cells were entrapped in hydrogels based on fibrin and plasmonic gold nanoparticles that transduced incident energy of an NIR laser into heat. In the presence of dimerizer, photoinduced mild hyperthermia induced the release of bioactive BMP-2 from NIR-responsive cell constructs. A critical size bone defect, created in calvaria of immunocompetent mice, was filled with NIR-responsive hydrogels entrapping cells that expressed BMP-2 under the control of the heat-activated and dimerizer-dependent gene circuit. In animals that were treated with dimerizer, NIR irradiation of implants induced BMP-2 production in the bone lesion. Induction of NIR-responsive cell constructs conditionally expressing BMP-2 in bone defects resulted in the formation of new mineralized tissue, thus indicating the therapeutic potential of the technological platform.

Thanks to the participation of NANBIOSIS U9 Synthesis of Nanoparticles Unit it has been possible to explore the use of gold plasmonic nanoparticles, capable of absorbing light in the near-infrared (NIR) area and converting it into heat

Article of reference:

Sánchez-Casanova, S., Martin-Saavedra, F.M., Escudero-Duch, C., Falguera Uceda, M.I., Prieto, M., Arruebo, M., Acebo, P., Fabiilli, M.L., Franceschi, R.T., Vilaboa, N. Local delivery of bone morphogenetic protein-2 from near infrared-responsive hydrogels for bone tissue regeneration. Biomaterials 241:119909. https://doi.org/10.1016/j.biomaterials.2020.119909

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Why the poor biodistribution so far reached by tumor-targeted medicines?

Cell-selective targeting is expected to enhance effectiveness and minimize side effects of cytotoxic agents. Functionalization of drugs or drug nanoconjugates with specific cell ligands allows receptor-mediated selective cell delivery. However, it is unclear whether the incorporation of an efficient ligand into a drug vehicle is sufficient to ensure proper biodistribution upon systemic administration, and also at which extent biophysical properties of the vehicle may contribute to the accumulation in target tissues during active targeting. To approach this issue, structural robustness of self-assembling, protein-only nanoparticles targeted to the tumoral marker CXCR4 is compromised by reducing the number of histidine residues (from six to five) in a histidine-based architectonic tag. Thus, the structure of the resulting nanoparticles, but not of building blocks, is weakened. Upon intravenous injection in animal models of human CXCR4+ colorectal cancer, the administered material loses the ability to accumulate in tumor tissue, where it is only transiently found. It instead deposits in kidney and liver. Therefore, precise cell-targeted delivery requires not only the incorporation of a proper ligand that promotes receptor-mediated internalization, but also, unexpectedly, its maintenance of a stable multimeric nanostructure that ensures high ligand exposure and long residence time in tumor tissue.

Protein production has been partially performed by the  ICTS NANBIOSIS U1, Protein Production Platform and the nanoparticle size analysis by the U6  of NANBIOSIS Biomaterial Processing and Nanostructuring Unit. Biodistribution studies were performed by the U18 of the ICTS NANBIOSIS, Nanotoxicology Unit.

The concept presented by the authors of the present research might represent a convincing explanation of the poor biodistribution so far reached by tumor-targeted medicines, including antibody-drug conjugates. In addition to this, they offer a potential developmental roadmap for the improvement of these drugs, of high intrinsic therapeutic potential, to reach satisfactory efficiencies in the clinical context.

Hèctor López-Laguna, Rita Sala, Julieta M. Sánchez, Patricia Álamo, Ugutz Unzueta, Alejandro Sánchez-Chardi, Naroa Serna, Laura Sánchez-García, Eric Voltà-Durán, Ramón Mangues, Antonio Villaverde and Esther Vázquez. Nanostructure Empowers Active Tumor Targeting in Ligand-Based Molecular Delivery. Part. Part. Syst. Charact. 2019.

DOI: 10.1002/ppsc.201900304

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NANOMOL group, coordinator of NANBIOSIS Unit 6 collaborates with the VHIR in the developement of a new nanomedicine for the treatment of a childhood cancer

Within the MOTHER project (Molecule-based materials and supramolecular organizations for therapy, diagnosis and tissue engineering), the NANOMOL group from ICMAB collaborates with the Vall d’Hebron Institute of Research (VHIR), on the developement of a new nanomedicine for the treatment of high risk neuroblastoma, one of the most typical childhood cancers. Now, researchers from VHIR have identified new microRNAs that reduce the progression of this type of cancer.

The participation of NANOMOL group and NANBIOSIS unit 6 Biomaterial Processing and Nanostructuring Unit, as experts in nanoparticles and nanovesciles for nanomedicine, is on the synthesis of the adequate nanocapsules to protect, stabilize and direct this microRNAs molecules to the cancer tumours. The near future goal is to be able to administer the identified microRNAs for the treatment of high-risk neuroblastoma.

For further information

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Nanoparticle uptake and in vivo estimates of therapeutic efect and toxicity

Ramón Mangues, Scientific Dierctor of unit 18 of NANBIOSIS, Unit of nanotoxicology, explains in this video some of the animal models used in the unit for preclinical validation of nanoparticles, especially of application in cancer

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Intracellular trafficking of a dynein-based nanoparticle designed for gene delivery

Unit 1 of NANBIOSIS, Protein Production Platform (PPP) and the  Nanobiotechnology research group of CIBER-BBN in collaboration with the Universidade Estadual de Campinas and the Universidade de São Paulo have recently published, in the European Journal of Pharmaceutical Sciences, the results of the research devoted to the improvement of protein-only based nanoconjugates for gene therapy. The evaluated gene-therapy vehicle prototype  displayed a similar transfection efficiency to that of the commercial vector LipofectamineTM 2000.

Article of reference:

https://doi.org/10.1016/j.ejps.2017.11.002

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Nanoparticles capable of bi-directional communication

The results of a research co-led by Ramón Martínez-Máñez, Scientific Director of Unit 26 of NANBIOSIS and CIBER-BBN have been published by Nature Communication last May 30th, showing how to prepare a nanoparticles chemical communication system using lactose. So far, his group had managed to establish communication between three nanoparticles but only in a unidirectional way. “We have managed to get a nanoparticle to send a chemical messenger to the second nanoparticle, who understands the message and sends another chemical messenger back to the first one. Upon receiving it, it performs an action, in this case releasing a dye,” explains Martínez-Máñezto Efefuturo.

This is a very important “basic” research due to the lack of proven results at the nanoscopic level. This research is the first step in getting the nanoparticles to work in a collaborative and coordinated way, anticipating a future of intelligent nanoparticle networks and advanced controlled release systems, drugs or complex systems based on nanotechnology.

The characterization of the system has been done with NMR unit of NANBIOSIS

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