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Posts Taged breast-cancer

New therapy for triple negative breast cancer is successfully tested in preclinical animals

Researchers CIBER-BBN and NANBIOSIS Unit 26, the Príncipe Felipe Research Center (CIPF), the Universitat Politècnica de València (UPV) and the Institut de Recerca Biomèdica (IRB) of Barcelona manage to inhibit tumor growth, reduce metastasis and decrease the toxicity of the antitumor drug Navitoclax in preclinical animal models of triple negative breast cancer (TNBC).

These types of TNBC tumors do not express any of the three receptors involved in most breast cancers (estrogen, progesterone, and HER2), so the most common treatments such as hormone therapy are not viable in these patients.

This new study, led by Mar Orzáez, principal investigator of the CIPF Peptides and Proteins Laboratory and Ramón Martínez Máñez, scientific director of CIBER-BBN, NANBIOSIS Unit 26, member of the CIPF-UPV Joint Unit in Mechanisms of disease and Nanomedicine and researcher at the Interuniversity Institute of Research on Molecular Recognition and Technological Development (IDM) at UPV, shows that a combined treatment of a senescence inducer and a senolytic nanoparticle, selectively removes senescent cells, delays tumor growth and reduces metastasis in a mouse model of aggressive breast cancer.

Until now, the application of senescence inducers represents a successful treatment strategy in patients with breast cancer, although the accumulation of senescent cells in the body can sometimes promote tumor recurrence.

Cell senescence or aging takes place in both physiological and pathological situations. When a cell goes into senescence, it stops dividing and releases substances that cause inflammation.

When an uncontrolled accumulation of these senescent cells occurs, the excess of inflammatory factors can end up damaging healthy cells, thereby contributing to aging, the appearance of pathologies such as diabetes, neurodegenerative diseases or promoting the development of tumors and promoting metastasis.

With this new approach, after the induction of senescence, the cells are eliminated by treatment with a senolytic nanoparticle, and a new therapeutic opportunity opens up to improve the results in patients with breast cancer and a new combined treatment is proposed that may be relevant to other senescence-inducing chemotherapeutic drugs.

The results, published in the Journal of Controlled Release (JCR), offer new therapeutic approaches to advance in later phases and clinical trials and allow different tumor types to be addressed.

Orzáez and Máñez have pointed out that “the induction of senescence in tumors represents an advance in the treatment of cancer, which may be even greater in combination with this type of senolytic treatments that eliminate senescent cells and help reduce metastasis.”

Manuel Serrano from the Institut de Recerca Biomèdica (IRB) in Barcelona has also collaborated in the study.

Article of reference:

Irene Galiana, Beatriz Lozano-Torres, Mónica Sancho, María Alfonso, Andrea Bernardos, Viviana Bisbal, Manuel Serrano, Ramón Martínez-Máñez, Mar Orzáez, Preclinical antitumor efficacy of senescence-inducing chemotherapy combined with a nanoSenolytic, Journal of Controlled Release, Volume 323 https://doi.org/10.1016/j.jconrel.2020.04.045

Sourse of information: CIBER-BBN

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Targeting antitumoral proteins to breast cancer by local administration of functional inclusion bodies

Three units of NANBIOSIS have collaborated in obtaining the research results published in the article “Targeting Antitumoral Proteins to Breast Cancer by Local Administration of Functional Inclusion Bodies” published by Advanced Science

Protein production and DLS have been partially performed by the Unit 1 of ICTS NANBIOSIS Protein Production Platform (PPP) and the Unit 6 NANBIOBIS Biomaterial Processing and Nanostructuring Unit. Biodistribution and immunohistochemistry assays were performed at NANBIOSIS U20 In Vivo Experimental Platform/FVPR

Two structurally and functionally unrelated proteins, namely Omomyc and p31, are engineered as CD44‐targeted inclusion bodies produced in recombinant bacteria. In this unusual particulate form, both types of protein materials selectively penetrate and kill CD44+ tumor cells in culture, and upon local administration, promote destruction of tumoral tissue in orthotropic mouse models of human breast cancer. These findings support the concept of bacterial inclusion bodies as versatile protein materials suitable for application in chronic diseases that, like cancer, can benefit from a local slow release of therapeutic proteins.

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Ramon Martinez Mañez, Scientific Director of Unit 26 of NANBIOSIS, has participated in the development of  new nanodevices that allow the controlled release of drugs, namely doxorubicin, for therapies against breast cancer.

So far, the work has focused on cellular assays, with positive results, that could open new ways to improve the effectiveness of some drugs used in the treatment of breast cancer.

The main novelty of these nanodevices is that the molecule covering the nanodevice not only controls when the transported drugs are released, but also controls where they are released to direct them to cells expressing TLR3, a protein of the innate immune system overexpressed in some cell lines of breast cancer. Through this protein it is also launched a death signal that ends with the tumor cell.

Their study was published last January in Chemistry-A European Journal:

Ultimo A, Giménez C, Bartovsky P, Aznar E, Sancenón F, Marcos MD, Amorós P, Bernardo AR, Martínez-Máñez R, Jiménez-Lara AM, Murguía JR.Targeting Innate Immunity with dsRNA-Conjugated Mesoporous Silica Nanoparticles Promotes Antitumor Effects on Breast Cancer Cells. Chemistry. Chemistry – A European Journal. DOI: 10.1002/chem.201504629

Nanbiosis_U26_New nanodevices to improve therapy for breast cancer
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