+34 9340006100 -ext. 437807-info@nanbiosis.com

Posts Taged cancer-diagnosis

A discovery in one of the most aggressive cancers will allow more efficient diagnosis

The extracellular vesicles secreted by triple-negative breast cancer stem cells are markers of lung metastasis, according to a study carried out by researchers at CIBER.

The work has been carried out by researchers from various CIBER-BBN groups (Bioengineering, Biomaterials and Nanomedicia), and CIBERONC (CIBER area focused on cancer) has participated in it. The research has been led by Joaquín Seras, from the Vall d’Hebron Research Institute (VHIR), a specialist in targeted drug therapies.

Physicochemical EVs characterization and all the in vivo studies were performed by NANBIOSISunits of CIBER, specifically NTA analysis was carried out at Unit 6 of Biomaterial Processing and Nanostructuring, led by Nora Ventosa at ICMB-CSIC and animal experimentation at Unit 20 “In vivo experimental platform”, led by Ibane Abasolo at VHIR.

The vesicle, in cell biology, is an organelle that forms a small, closed compartment, separated from the cytoplasm by a lipid bilayer just like the cell membrane. The vesicles store, transport or digest cellular products and waste. According to Joaquin Seras, leader of the research: “the identification of this subpopulation of cancerous extracellular vesicles, and their important role in the progression of the disease, will allow in the future to develop systems more effective and less invasive diagnostic methods based on their detection directly from blood samples”.

In different types of tumors, including triple negative breast cancer, it has been observed that the extracellular vesicles generated by tumor cells play an important role in the generation of pre-metastatic niches. Triple negative breast cancer, one of the most aggressive, highly plastic and heterogeneous, is characterized by a significant presence of malignant stem cells.

The study carried out by the Spanish researchers from CIBER with promising results, published in the “International Journal of Cancer”, shows, both in in vitro and in vivo models of the disease, that the vesicles actively contribute to the formation of areas with favorable conditions for the formation of metastases, thus favoring way, the spread of the disease.

Research contributions
In the opinion of Joaquin Seras, the great contribution of this work is that it “describes how the extracellular vesicles secreted by certain subpopulations of cancer cells, specifically those derived from cancer stem cells, have the potential to modify the microenvironment of the future metastatic niche to promote tumor growth.

In other words, continues the leader of the study: “the research sheds new information on the pathogenic mechanism of the disease, and suggests these extracellular vesicles as markers with diagnostic potential. It should be noted that these nanoparticles are secreted into the bloodstream by tumor cells, and effective capture and identification would allow them to be exploited as a diagnostic tool”.

On the characterization of extracellular vesicles of cancer cells
The complex composition and functional differentiation of cancer cells in a tumor also increases the heterogeneity of the subsets of vesicles secreted by cancer.

This phenomenon is particularly relevant in triple negative breast cancer, one of the most aggressive, highly plastic and heterogeneous cancers, characterized by a significant presence of malignant stem cells. However, until now the diversity of the vesicles secreted by cancer cells had not been studied, a diversity that is closely related, in turn and as the study shows, to cellular heterogeneity in triple-negative tumors.

The importance of the CIBER study lies at this point: the vesicles secreted by different tumor subpopulations and grouped by their degree of differentiation show fundamentally different activities in terms of their impact on cancer progression.

In the investigation, the extracellular vesicles secreted by up to three different types of neoplastic cells have been isolated and characterized, observing different bioburdens for each type, with the consequent differential effect on stromal cells. In addition, and as the study shows, cancer stem cell-derived vesicles contribute to converting healthy lung cells into receptive niches for the metastatic growth of cancerous breast cells.

Article reference:

González-Callejo P, Gener P, Díaz-Riascos ZV, Conti S, Cámara-Sánchez P, Riera R, Mancilla S, García-Gabilondo M, Peg V, Arango D, Rosell A, Labernadie A, Trepat X, Albertazzi L, Schwartz S Jr, Seras-Franzoso J, Abasolo I. Extracellular vesicles secreted by triple-negative breast cancer stem cells trigger premetastatic niche remodeling and metastatic growth in the lungs. Int J Cancer. 2023 Jan 27. doi: 10.1002/ijc.34447. Epub ahead of print. PMID: 36705298.

Read More

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

Read More

3D bioprinting applied to cancer diagnostics

Mateu Pla Roca, Scientific Coordinator of Unit 7 of NANBIOSIS /IBEC Core Facilities has won CaixaImpulse funding for his project “3D bioprinted array tissue-like cores: tissue-like controls for cancer diagnostics” (3DBIOcores), which will be carried out in collaboration with Antoni Martinez, head of the histopathology service at Hospital Clinic. CaixaImpulse programme aims to promote technology transfer in science.

The project 3DBIOcores will take advantage of 3D bioprinting to create quality control samples that assure and improve cancer diagnostics. Usually, diagnosis is done by histopathology – the microscopic examination of tissues – and then the biomarkers that are found are quantified. However, histological techniques face some degree of variability that can lead to misinterpretation, and for this reason, such tests require quality control samples to be processed side-by-side with patient samples to verify the final diagnosis.

Currently, hospitals use surplus human tissue which is known to express the required biomarkers as quality control samples, but these are scarce and non-homogeneous, and their use raises ethical issues. Mateu’s project proposes 3DBIOcores as a new source of these essential controls. Taking advantage of 3D bioprinting technology, tissue-like structures containing cell lines with relevant cancer biomarkers will be produced and used as a new source of control samples.

“3DBIOcores will be a real innovation in histopathology analysis, with the potential to have an enormous impact on cancer diagnosis based on the histopathological analysis of biopsies, improving precision in cancer treatment and reducing diagnostic errors,” says Mateu.

Read More

A multiplexing nanophotonic biosensor for cancer diagnosis

The group Biosensors and bio-analytic applications, led by Laura Lechuga,​ coordinator of Unit 4 of NANBIOSIS, has developed a methodology through a nano-photonic sensor (known as bimodal waveguide interferometer) capable of quantifying, directly and mark-free, the different messenger RNA isoforms generated by alternative splicing.

The expertise in biodeposition and biodetection systems of Lechuga’s group has permitted a thorough analytical study and optimization of the methodology, achieving not only total selectivity, but also excellent levels of sensitivity and reproducibility, and obtaining the lowest levels of detection in direct detection of messenger RNA isoforms generated by this mechanism without the need for PCR amplification (polymerase chain reaction).

The results of the study have recently been published in Scientific Reports (of the Nature group) and show a new methodology for the analysis of alternative splicing processes in a fast, simple and direct way, overcoming the main problems of conventional techniques. In addition, it opens the possibility of developing more efficient tools for the diagnosis and monitoring of therapy, providing a more informative, specific and precise analysis.

Article of reference:

Analysis of alternative splicing events for cancer diagnosis using a multiplexing nanophotonic biosensor. Scientific Reports 7, Article number: 41368 (2017) doi:10.1038/srep41368.

A multiplexing nanophotonic biosensor for cancer diagnosis
Read More