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Posts on Jan 1970

A new smart drug that finds and kills metastasis cells could be applied in 23 types of cancer

Researchers of two CIBER-BBN Units of the ICTS NANBIOSIS  U18 Nanotoxicology Unit at Hospital Sant Pau. and U1, Protein Production Platform (PPP), at the  Institute of Biotechnology and biomedicine of the Autonomous University of Barcelona (IBBUAB), led by Prof Ramón Mangues, have developed a new drug that selectively removes metastatic stem cells, inducing a powerful metastasis prevention effect.

Besides the participation of the “NANBIOSIS” ICTS Units
U1 Protein Production Platform where Protein production was partially performed and U18 Nantoxicology Unit where Biodistribution studies were performed, all in vivo experiments were performed by the Unit 20 In Vivo Experimental Platform of CIBER in Bioengineering, Biomaterials & Nanomedicine (CIBER-BBN)

The researchers have ceated inclusion bodies of amyloid and nanostructured fibers that, when administered subcutaneously in mice, release soluble cytotoxic nanoparticles continuously. These nanoparticles are carriers of the exotoxin of Pseudomonas aeruginosa that manages to maintain a stable concentration of this nanomedicine in the blood and tissues. Dr. Mangues explains that “this new pharmaceutical form of subcutaneous administration for sustained release allows high doses of this nanopharmaceutical to be administered, at prolonged intervals (weeks in mice and probably months in humans) without toxicity at the injection site or in normal tissues, while generating a powerful antimetastatic effect. Apart from being controlled-release systems, these nanoparticles incorporate a ligand that interacts with the receptor (CXCR4), present at high levels in the membrane of metastatic stem cells capable of generating metastases (CMM CXCR4 +). Once the new pharmaceutical form is administered subcutaneously in mice with metastatic colorectal cancer, this ligand directs each nanoparticle released by this structure to the tumor tissues, increasing their uptake, to specifically internalize in the CXCR4 + CMMs and induce their selective destruction. “This effect achieves a notable reduction in tumor size in the colon while blocking the development of lymph node, lung, liver and peritoneal metastases, without appreciable uptake or toxicity in non-tumor tissues” continous the researchers.

The researchers estimate that this new therapeutic strategy will have a high clinical impact by reducing the requirement of its hospital administration, which most antitumor drugs have, and blocking metastatic dissemination, responding to an unmet clinical need. On the other hand, this new pharmaceutical form, which combines sustained release with targeting to the CXCR4 receptor, could be used in the treatment of at least 23 types of cancer that also express high levels of this receptor in tumor cells.

The new therapy offers an answer to the urgent medical need to inhibit the development of metastases, which represents the leading cause of death in cancer patients. The selective destruction of tumor and metastatic cells increases the therapeutic index of nanomedicine, obtaining a potent antimetastatic effect without generating associated adverse effects, which differentiates it from most of the currently used antitumor drugs.


Article of reference

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. Engineering Secretory Amyloids for Remote and Highly Selective Destruction of Metastatic Foci Adv.Mater.2019, 1907348

https://doi.org/10.1002/adma.201907348

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Ethylcellulose nanoparticles as new “in vitro” tool for cell transfection

Researchers of NANBIOSIS U12 Nanostructured liquid characterization unit and U29 Oligonucleotide Synthesis Platform (OSP) of CIBER-BBN at IQAC-CSIC have obtained successfully ethylcellulose nanoparticles with positive zeta potential formed from nano-emulsion complexation with an antisense oligonucleotide which result very promising complexes for “in vitro” cell transfection.

A new non-viral gene delivery vector has been developed, based on ethylcellulose, an easily available and low cost carbohydrate polymer, “generally recognized as safe” by the FDA. Although ethylcellulose is nonionic, positively charged nanoparticle dispersions have been obtained using nano-emulsion templates in cationic:non-ionic surfactant-based systems. The nanoparticles have been successfully complexed with negatively charged phosphorothioate antisense oligonucleotides. These short nucleic acid chains are advantageous as they show improved cell penetration ability and higher resistance to degradation by nucleases. The nanoparticle:oligonucleotide complexes obtained show suitable transfection efficiency and are promising for “in vitro” gene transfection purposes.

This research has been developed through the close collaboration between the Colloidal and Interfacial Chemistry group led by Dr. Carlos Rodríguez Abreu, and the Nucleic Acids Chemistry group led by Dr. Ramon Eritja as well as the NANBIOSIS U12 and U29 Units. Both groups belong to the Institute of Advanced Chemistry of Catalonia (IQAC-CSIC) and the CIBER-BBN.

Article of reference: Leitner, S.; Grijalvo, S.; Solans, C.; Eritja, R.; Garcia-Celma, M. J.; Caldero, G., Ethylcellulose nanoparticles as a new “in vitro” transfection tool for antisense oligonucleotide delivery CARBOHYDRATE POLYMERS 229,1, 115451, 2020; DOI: 10.1016/j.carbpol.2019.115451

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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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