Paradoxical cell targeting of calreticulin-empowered, protein-only nanoparticles
Surface-exposed calreticulin (CRT) serves as a crucial cell damage-associated molecular pattern for immunogenic apoptosis, by generating an "eat me" signal to macrophages. Aiming at precision immunotherapies we intended to artificially label tumoral cells in vivo with a recombinant CRT, in a targete...
| Autores: | ; ; ; ; ; ; ; |
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| Tipo de documento: | Artículo |
| Fecha de publicación: | 2024 |
| País: | España |
| Institución: | Universitat Autònoma de Barcelona |
| Repositorio: | Dipòsit Digital de Documents de la UAB |
| Lenguaje: | Inglés |
| OAI Identifier: | oai:ddd.uab.cat:300320 |
| Acceso en línea: | https://ddd.uab.cat/record/300320 https://dx.doi.org/urn:doi:10.1016/j.ejpb.2024.114410 |
| Nivel de acceso: | Acceso abierto |
| Palabra clave: | Recombinant proteins Protein materials Nanoparticles Drug delivery Cell targeting |
| _version_ | 1878735309282213888 |
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| author | Parladé Molist, Eloi|||0000-0001-5750-550X |
| author2 | Garcia León, Annabel|||0000-0003-3007-9306 Voltà-Durán, Eric|||0000-0003-0017-8274 Unzueta Elorza, Ugutz|||0000-0001-5119-2266 Mangues, Ramon|||0000-0003-2661-9525 Casanova Rigat, Isolda|||0000-0002-1196-4724 Villaverde, Antonio|||0000-0002-2615-4521 Vázquez, Esther|||0000-0003-1052-0424 |
| author2_role | author author author author author author author |
| author_browse | Casanova Rigat, Isolda|||0000-0002-1196-4724 Garcia León, Annabel|||0000-0003-3007-9306 Mangues, Ramon|||0000-0003-2661-9525 Parladé Molist, Eloi|||0000-0001-5750-550X Unzueta Elorza, Ugutz|||0000-0001-5119-2266 Villaverde, Antonio|||0000-0002-2615-4521 Voltà-Durán, Eric|||0000-0003-0017-8274 Vázquez, Esther|||0000-0003-1052-0424 |
| author_facet | Parladé Molist, Eloi|||0000-0001-5750-550X Garcia León, Annabel|||0000-0003-3007-9306 Voltà-Durán, Eric|||0000-0003-0017-8274 Unzueta Elorza, Ugutz|||0000-0001-5119-2266 Mangues, Ramon|||0000-0003-2661-9525 Casanova Rigat, Isolda|||0000-0002-1196-4724 Villaverde, Antonio|||0000-0002-2615-4521 Vázquez, Esther|||0000-0003-1052-0424 |
| author_role | author |
| collection | Dipòsit Digital de Documents de la UAB |
| description | Surface-exposed calreticulin (CRT) serves as a crucial cell damage-associated molecular pattern for immunogenic apoptosis, by generating an "eat me" signal to macrophages. Aiming at precision immunotherapies we intended to artificially label tumoral cells in vivo with a recombinant CRT, in a targeted way. For that, we have constructed a CRT fusion protein intended to surface attach CXCR4 cancer cells, to stimulate their immunological destruction. As a targeting ligand of the CRT construct and to drive its specific cell adhesion, we used the peptide V1, a derivative of the vMIP-II cytokine and an antagonist of CXCR4. The modular protein tends to self-assemble as regular 16 nm nanoparticles, assisted by ionic Zn. Through both in vivo and in vitro experiments, we have determined that CRT itself confers cell targeting capabilities to the construct overcoming those of V1, that are only moderate. In particular, CRT binds HeLa cells in absence of further internalization, by a route fully independent of CXCR4. Furthermore, by cytometry in THP-1 cells, we observed that the binding of the protein is preferential for dead cells over live cells, a fact that cannot be associated to a mere artefactual adsorption. These data are discussed in the context of the oligomerizing properties of CRT and the potential clinical applicability of proteins and protein materials functionalized with this novel cell surface ligand. |
| eu_rights_str_mv | openAccess |
| format | article |
| id | ES_7a3290c0f8df23bae5aaac8f9f6653f7 |
| institution | Universitat Autònoma de Barcelona |
| instname_str | Universitat Autònoma de Barcelona |
| language | eng |
| network_acronym_str | ES |
| network_name_str | España |
| oai_identifier_str | oai:ddd.uab.cat:300320 |
| publishDate | 2024 |
| publishDateSort | 2024 |
| reponame_str | Dipòsit Digital de Documents de la UAB |
| spelling | Paradoxical cell targeting of calreticulin-empowered, protein-only nanoparticles Parladé Molist, Eloi|||0000-0001-5750-550X Garcia León, Annabel|||0000-0003-3007-9306 Voltà-Durán, Eric|||0000-0003-0017-8274 Unzueta Elorza, Ugutz|||0000-0001-5119-2266 Mangues, Ramon|||0000-0003-2661-9525 Casanova Rigat, Isolda|||0000-0002-1196-4724 Villaverde, Antonio|||0000-0002-2615-4521 Vázquez, Esther|||0000-0003-1052-0424 Recombinant proteins Protein materials Nanoparticles Drug delivery Cell targeting Surface-exposed calreticulin (CRT) serves as a crucial cell damage-associated molecular pattern for immunogenic apoptosis, by generating an "eat me" signal to macrophages. Aiming at precision immunotherapies we intended to artificially label tumoral cells in vivo with a recombinant CRT, in a targeted way. For that, we have constructed a CRT fusion protein intended to surface attach CXCR4 cancer cells, to stimulate their immunological destruction. As a targeting ligand of the CRT construct and to drive its specific cell adhesion, we used the peptide V1, a derivative of the vMIP-II cytokine and an antagonist of CXCR4. The modular protein tends to self-assemble as regular 16 nm nanoparticles, assisted by ionic Zn. Through both in vivo and in vitro experiments, we have determined that CRT itself confers cell targeting capabilities to the construct overcoming those of V1, that are only moderate. In particular, CRT binds HeLa cells in absence of further internalization, by a route fully independent of CXCR4. Furthermore, by cytometry in THP-1 cells, we observed that the binding of the protein is preferential for dead cells over live cells, a fact that cannot be associated to a mere artefactual adsorption. These data are discussed in the context of the oligomerizing properties of CRT and the potential clinical applicability of proteins and protein materials functionalized with this novel cell surface ligand. https://ddd.uab.cat/record/300320 https://dx.doi.org/urn:doi:10.1016/j.ejpb.2024.114410 |
| spellingShingle | Paradoxical cell targeting of calreticulin-empowered, protein-only nanoparticles Parladé Molist, Eloi|||0000-0001-5750-550X Recombinant proteins Protein materials Nanoparticles Drug delivery Cell targeting |
| title | Paradoxical cell targeting of calreticulin-empowered, protein-only nanoparticles |
| title_full | Paradoxical cell targeting of calreticulin-empowered, protein-only nanoparticles |
| title_fullStr | Paradoxical cell targeting of calreticulin-empowered, protein-only nanoparticles |
| title_full_unstemmed | Paradoxical cell targeting of calreticulin-empowered, protein-only nanoparticles |
| title_short | Paradoxical cell targeting of calreticulin-empowered, protein-only nanoparticles |
| title_sort | Paradoxical cell targeting of calreticulin-empowered, protein-only nanoparticles |
| topic | Recombinant proteins Protein materials Nanoparticles Drug delivery Cell targeting |
| topic_facet | Recombinant proteins Protein materials Nanoparticles Drug delivery Cell targeting |
| url | https://ddd.uab.cat/record/300320 https://dx.doi.org/urn:doi:10.1016/j.ejpb.2024.114410 |