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| Home > Articles > Published articles > Lymphocyte infiltration and antitumoral effect promoted by cytotoxic inflammatory proteins formulated as self-assembling, protein-only nanoparticles |
| Home > Articles > Published articles > Lymphocyte infiltration and antitumoral effect promoted by cytotoxic inflammatory proteins formulated as self-assembling, protein-only nanoparticles |
(Universitat Autònoma de Barcelona. Institut de Biotecnologia i de Biomedicina "Vicent Villar Palasí") (Institut Germans Trias i Pujol. Institut de Recerca contra la Leucèmia Josep Carreras) (Institut Germans Trias i Pujol. Institut de Recerca contra la Leucèmia Josep Carreras) (Universitat Autònoma de Barcelona. Institut de Biotecnologia i de Biomedicina "Vicent Villar Palasí") (Institut d'Investigació Biomèdica Sant Pau) (Institut Germans Trias i Pujol. Institut de Recerca contra la Leucèmia Josep Carreras) (Institut d'Investigació Biomèdica Sant Pau) (Universitat Autònoma de Barcelona. Departament de Genètica i de Microbiologia) (Institut d'Investigació Biomèdica Sant Pau) (Universitat Autònoma de Barcelona. Institut de Biotecnologia i de Biomedicina "Vicent Villar Palasí")
| Date: | 2023 |
| Abstract: | Two human proteins involved in the inflammatory cell death, namely Gasdermin D (GSDMD) and the Mixed Lineage Kinase Domain-Like (MLKL) protein have been engineered to accommodate an efficient ligand of the tumoral cell marker CXCR4, and a set of additional peptide agents that allow their spontaneous self-assembling. Upon production in bacterial cells and further purification, both proteins organized as stable nanoparticles of 46 and 54 nm respectively, that show, in this form, a moderate but dose-dependent cytotoxicity in cell culture. In vivo, and when administered in mouse models of colorectal cancer through repeated doses, the nanoscale forms of tumor-targeted GSDMD and, at a lesser extent, of MLKL promoted CD8+ and CD20+ lymphocyte infiltration in the tumor and an important reduction of tumor size, in absence of systemic toxicity. The potential of these novel pharmacological agents as anticancer drugs is discussed in the context of synergistic approaches to more effective cancer treatments. |
| Grants: | Agencia Estatal de Investigación PID2019-105416RB-I00 Agencia Estatal de Investigación PDC2022-133858-I00 Agencia Estatal de Investigación PID2020-116174RB-I00 Agència de Gestió d'Ajuts Universitaris i de Recerca 2021/SGR-00092 Instituto de Salud Carlos III P21/00150 Instituto de Salud Carlos III PI20/00400 Ministerio de Sanidad y Consumo CB06/01/0014 Instituto de Salud Carlos III CB06/01/1031 Instituto de Salud Carlos III CP19/00028 |
| Rights: | Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, i la comunicació pública de l'obra, sempre que no sigui amb finalitats comercials, i sempre que es reconegui l'autoria de l'obra original. No es permet la creació d'obres derivades.  |
| Language: | Anglès |
| Document: | Article ; recerca ; Versió publicada |
| Subject: | Recombinant proteins ; Biomaterials ; Nanoparticles ; Pyroptosis ; Cancer ; Drug delivery ; Gasdermin D |
| Published in: | Biomedicine & pharmacotherapy, Vol. 164 (August 2023) , art. 114976, ISSN 1950-6007 |
| Related work: | Martínez-Torró, Carlos; Alba-Castellón, Lorena; Carrasco-Díaz, Luis Miguel; Serna, Naroa; Imedio, Laura; Gallardo, Alberto; Casanova Rigat, Isolda; Unzueta, Ugutz; Vazquez, Esther; Mangues, Ramon; Villaverde, Antonio, 2023, "Biological effects of cytotoxic inflammatory proteins formulated as self-assembling, protein-only nanoparticles", CORA.Repositori de Dades de Recerca https://doi.org/10.34810/data735 |
