U18. Nanotoxicology Unit

U18-S05. Histological analyses

Histological analyses

The aim of this service is to evaluate the toxicity or antitumor activity of nanoparticles and drug-loaded nanoparticles in normal or tumor tissues provided by the customer or obtained in the in vivo assays performed in the unit. The histological analyses that we offer include hematoxylin&eosin staining to evaluate the toxicity in normal tissues and also the mitotic index or cell death present in tumor tissues. We also offer DAPI staining of tissue samples to evaluate apoptosis induction by compounds. Moreover, we also offer the study of the expression of different markers by Immunohistochemistry. Thus, we offer the evaluation of different cell death (PARP, Caspases, …) or proliferation (Ki67, Cyclins,…) markers. We can also offer the possibility to set up the evaluation of new markers of interest by the costumer.

Customer benefits

The costumer will benefit from the experience of the researchers involved in the service performing histological analyses of normal and tumor tissues. The service has also high expertise in immunohistochemistry staining and offers the possibility of setting up new antibodies that can be of interest for the costumer.

Target customer

The offered service can be of interest to research groups of academia or companies willing to study the histology of normal or tumor tissue samples.

References

Martínez-Torró C, Alba-Castellón L, Carrasco-Díaz LM, Serna N, Imedio L, Gallardo A, Casanova I, Unzueta U, Vázquez E, Mangues R, Villaverde A. Lymphocyte infiltration and antitumoral effect promoted by cytotoxic inflammatory proteins formulated as self-assembling, protein-only nanoparticles. Biomed Pharmacother. 2023 Aug;164:114976. doi: 10.1016/j.biopha.2023.114976.
Falgàs A, Garcia-León A, Núñez Y, Serna N, Sánchez-Garcia L, Unzueta U, Voltà-Durán E, Aragó M, Álamo P, Alba-Castellón L, Sierra J, Gallardo A, Villaverde A, Vázquez E, Mangues R, Casanova I. A diphtheria toxin-based nanoparticle achieves specific cytotoxic effect on CXCR4+ lymphoma cells without toxicity in immunocompromised and immunocompetent mice. Biomed Pharmacother. 2022 Jun;150:112940. doi: 10.1016/j.biopha.2022.112940.
-Medina-Gutiérrez E, García-León A, Gallardo A, Álamo P, Alba-Castellón L, Unzueta U, Villaverde A, Vázquez E, Casanova I, Mangues R. Potent Anticancer Activity of CXCR4-Targeted Nanostructured Toxins in Aggressive Endometrial Cancer Models. Cancers (Basel). 2022 Dec 23;15(1):85. doi: 10.3390/cancers15010085.
Sala R, Rioja-Blanco E, Serna N, Sánchez-García L, Álamo P, Alba-Castellón L, Casanova I, López-Pousa A, Unzueta U, Céspedes MV, Vázquez E, Villaverde A, Mangues R. GSDMD-dependent pyroptotic induction by a multivalent CXCR4-targeted nanotoxin blocks colorectal cancer metastases. Drug Deliv. 2022 Dec;29(1):1384-1397. doi: 10.1080/10717544.2022.2069302.
Pallarès V, Unzueta U, Falgàs A, Aviñó A, Núñez Y, García-León A, Sánchez-García L, Serna N, Gallardo A, Alba-Castellón L, Álamo P, Sierra J, Cedó L, Eritja R, Villaverde A, Vázquez E, Casanova I, Mangues R. A multivalent Ara-C-prodrug nanoconjugate achieves selective ablation of leukemic cells in an acute myeloid leukemia mouse model. Biomaterials. 2022 Jan;280:121258. doi: 10.1016/j.biomaterials.2021.121258.

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U18-S04. In vitro Antitumor Activity

In vitro Antitumor Activity

The aim of this service is to evaluate the in vitro antitumor activity of compounds in different types of human cancer cell lines in which we determine the effect using different types of assays including MTT, LDH release and caspase activation. The cellular models that we offer include human cell lines from different tumor types including hematologic and solid neoplasias.

Customer benefits

The costumer will benefit from more than 20 years of experience of the researchers involved in the service that have performed the in vitro evaluation of the antitumor activity of different nanoparticles and other types of compounds. We offer also the possibility of setting up new in vitro assays or to offer other cellular models that could be of interest for the costumer. Moreover, the conditions of the assays are flexible and will be adapted to the needs of each specific compound.

Target customer

The offered service can be of interest to research groups of academia or companies willing to test the antitumor activity of any compound in vitro.

References

Falgàs A, Pallarès V, Unzueta U, Núñez Y, Sierra J, Gallardo A, Alba-Castellón L, Mangues MA, Álamo P, Villaverde A, Vázquez E, Mangues R, Casanova I. Specific Cytotoxic Effect of an Auristatin Nanoconjugate Towards CXCR4+ Diffuse Large B-Cell Lymphoma Cells. Int J Nanomedicine. 2021 Mar 5;16:1869-1888. doi: 10.2147/IJN.S289733.
Núñez Y, Garcia-León A, Falgàs A, Serna N, Sánchez-García L, Garrido A, Sierra J, Gallardo A, Unzueta U, Vázquez E, Villaverde A, Mangues R, Casanova I. T22-PE24-H6 Nanotoxin Selectively Kills CXCR4-High Expressing AML Patient Cells In Vitro and Potently Blocks Dissemination In Vivo. Pharmaceutics. 2023 Feb 22;15(3):727. doi: 10.3390/pharmaceutics15030727.
-Medina-Gutiérrez E, García-León A, Gallardo A, Álamo P, Alba-Castellón L, Unzueta U, Villaverde A, Vázquez E, Casanova I, Mangues R. Potent Anticancer Activity of CXCR4-Targeted Nanostructured Toxins in Aggressive Endometrial Cancer Models. Cancers (Basel). 2022 Dec 23;15(1):85. doi: 10.3390/cancers15010085.
Sala R, Rioja-Blanco E, Serna N, Sánchez-García L, Álamo P, Alba-Castellón L, Casanova I, López-Pousa A, Unzueta U, Céspedes MV, Vázquez E, Villaverde A, Mangues R. GSDMD-dependent pyroptotic induction by a multivalent CXCR4-targeted nanotoxin blocks colorectal cancer metastases. Drug Deliv. 2022 Dec;29(1):1384-1397. doi: 10.1080/10717544.2022.2069302.

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U18-S03. In vivo antitumor activity

In vivo antitumor activity

The aim of this service is to evaluate the biodistribution and/or the in vivo antitumor activity of nanoparticles and drug-loaded nanoparticles. Thus, we offer different tumor mouse models, subcutaneous and orthotopic, in which we can determine the biodistribution of nanoparticles, with or without loaded drug, in normal and tumor tissues. Moreover, we can also determine the antitumor activity of the compounds in different tumor models. In the service we have subcutaneous and orthotopic/disseminated models of lymphoma, leukemia and colorectal, endometrium, head and neck carcinomas. Moreover, we have also available PDX models of colorectal and endometrium cancer. We can also offer the possibility to set up new animal models of other tumor types.

Customer benefits

The customer will benefit from the experience of the researchers involved in the service that have performed the in vivo evaluation of a high number of diverse nanoparticles. The service has also high expertise in developing new cancer animal models. Thus, we offer also the possibility of setting up new models of any cancer type that fit with the needs of the costumer. Moreover, the conditions of the assays are flexible and will be adapted to the need of each specific compound.

Target customer

The offered service can be of interest to research groups of academia or companies willing to test the antitumor activity of nanoparticles or drug-loaded nanoparticles in vivo.

References

Martínez-Torró C, Alba-Castellón L, Carrasco-Díaz LM, Serna N, Imedio L, Gallardo A, Casanova I, Unzueta U, Vázquez E, Mangues R, Villaverde A. Lymphocyte infiltration and antitumoral effect promoted by cytotoxic inflammatory proteins formulated as self-assembling, protein-only nanoparticles. Biomed Pharmacother. 2023 Aug;164:114976. doi: 10.1016/j.biopha.2023.114976.
Rioja-Blanco E, Arroyo-Solera I, Álamo P, Casanova I, Gallardo A, Unzueta U, Serna N, Sánchez-García L, Quer M, Villaverde A, Vázquez E, Mangues R, Alba-Castellón L, León X. Self-assembling protein nanocarrier for selective delivery of cytotoxic polypeptides to CXCR4+ head and neck squamous cell carcinoma tumors. Acta Pharm Sin B. 2022 May;12(5):2578-2591. doi: 10.1016/j.apsb.2021.09.030.
Falgàs A, Garcia-León A, Núñez Y, Serna N, Sánchez-Garcia L, Unzueta U, Voltà-Durán E, Aragó M, Álamo P, Alba-Castellón L, Sierra J, Gallardo A, Villaverde A, Vázquez E, Mangues R, Casanova I. A diphtheria toxin-based nanoparticle achieves specific cytotoxic effect on CXCR4+ lymphoma cells without toxicity in immunocompromised and immunocompetent mice. Biomed Pharmacother. 2022 Jun;150:112940. doi: 10.1016/j.biopha.2022.112940.
-Medina-Gutiérrez E, García-León A, Gallardo A, Álamo P, Alba-Castellón L, Unzueta U, Villaverde A, Vázquez E, Casanova I, Mangues R. Potent Anticancer Activity of CXCR4-Targeted Nanostructured Toxins in Aggressive Endometrial Cancer Models. Cancers (Basel). 2022 Dec 23;15(1):85. doi: 10.3390/cancers15010085.
Sala R, Rioja-Blanco E, Serna N, Sánchez-García L, Álamo P, Alba-Castellón L, Casanova I, López-Pousa A, Unzueta U, Céspedes MV, Vázquez E, Villaverde A, Mangues R. GSDMD-dependent pyroptotic induction by a multivalent CXCR4-targeted nanotoxin blocks colorectal cancer metastases. Drug Deliv. 2022 Dec;29(1):1384-1397. doi: 10.1080/10717544.2022.2069302.
Serna N, Falgàs A, García-León A, Unzueta U, Núñez Y, Sánchez-Chardi A, Martínez-Torró C, Mangues R, Vazquez E, Casanova I, Villaverde A. Time-Prolonged Release of Tumor-Targeted Protein-MMAE Nanoconjugates from Implantable Hybrid Materials. Pharmaceutics. 2022 Jan 14;14(1):192. doi: 10.3390/pharmaceutics14010192.
Pallarès V, Unzueta U, Falgàs A, Aviñó A, Núñez Y, García-León A, Sánchez-García L, Serna N, Gallardo A, Alba-Castellón L, Álamo P, Sierra J, Cedó L, Eritja R, Villaverde A, Vázquez E, Casanova I, Mangues R. A multivalent Ara-C-prodrug nanoconjugate achieves selective ablation of leukemic cells in an acute myeloid leukemia mouse model. Biomaterials. 2022 Jan;280:121258. doi: 10.1016/j.biomaterials.2021.121258.

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