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Self-assembled nanobodies as selectively targeted, nanostructured, and multivalent materials
Sánchez-García, Laura (Universitat Autònoma de Barcelona. Institut de Biotecnologia i de Biomedicina "Vicent Villar Palasí")
Voltà-Durán, Eric (Universitat Autònoma de Barcelona. Departament de Genètica i de Microbiologia)
Parladé Molist, Eloi (Universitat Autònoma de Barcelona. Institut de Biotecnologia i de Biomedicina "Vicent Villar Palasí")
Mazzega, Elisa (University of Nova Gorica. Laboratory for Environmental and Life Sciences (Slovenia))
Sánchez Chardi, Alejandro (Universitat Autònoma de Barcelona. Servei de Microscòpia)
Serna, Naroa (Universitat Autònoma de Barcelona. Institut de Biotecnologia i de Biomedicina "Vicent Villar Palasí")
López-Laguna, Hèctor (Universitat Autònoma de Barcelona. Institut de Biotecnologia i de Biomedicina "Vicent Villar Palasí")
Mitstorfer, Mara (University of Natural Resources and Life Sciences. Department of Chemistry (Austria))
Unzueta Elorza, Ugutz (Institut d'Investigació Biomèdica Sant Pau)
Vázquez Gómez, Esther (Universitat Autònoma de Barcelona. Institut de Biotecnologia i de Biomedicina "Vicent Villar Palasí")
Villaverde Corrales, Antonio (Universitat Autònoma de Barcelona. Institut de Biotecnologia i de Biomedicina "Vicent Villar Palasí")
de Marco, Ario (University of Nova Gorica. Laboratory for Environmental and Life Sciences (Slovenia))

Date: 2021
Abstract: Nanobodies represent valuable tools in advanced therapeutic strategies but their small size (∼2. 5 × ∼ 4 nm) and limited valence for interactions might pose restrictions for in vivo applications, especially regarding their modest capacity for multivalent and cooperative interaction. In this work, modular protein constructs have been designed, in which nanobodies are fused to protein domains to provide further functionalities and to favor oligomerization into stable self-assembled nanoparticles. The nanobody specificity for their targets is maintained in such supramolecular complexes. Also, their diameter around 70 nm and multivalent interactivity should favor binding and penetrability into target cells via solvent-exposed receptor. These concepts have been supported by unrelated nanobodies directed against the ricin toxin (A3C8) and the Her2 receptor (EM1), respectively, that were modified with the addition of a reporter protein and a hexa-histidine tag at the C-terminus that promotes self-assembling. The A3C8-based nanoparticles neutralize the ricin toxin efficiently, whereas the EM1-based nanoparticles enable to selective imaging Her2-positive cells. These findings support the excellent extracellular and intracellular functionality of nanobodies organized in form of oligomeric nanoscale assemblies.
Grants: Agencia Estatal de Investigación BIO2016-76063-R
Agència de Gestió d'Ajuts Universitaris i de Recerca 2017/SGR-229
Agència de Gestió d'Ajuts Universitaris i de Recerca 2018FI_B2_00051
Ministerio de Ciencia e Innovación FPU18/04615
Instituto de Salud Carlos III CP19/00028
Agència de Gestió d'Ajuts Universitaris i de Recerca 2019FI_B00352
Note: Altres ajuts: acords transformatius de la UAB
Note: Altres ajuts: EU COST Action CA 17140 ; ICREA Academia award
Rights: Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original. Creative Commons
Language: Anglès
Document: Article ; recerca ; Versió publicada
Subject: Nanobodies ; Self-assembling ; Ricin ; Nanoparticles ; Controlled delivery ; Biomaterials
Published in: ACS applied materials & interfaces, Vol. 13, Issue 25 (June 2021) , p. 29406-29415, ISSN 1944-8252

Dades de recerca relacionades amb l'article: https://ddd.uab.cat/record/264051
DOI: 10.1021/acsami.1c08092
PMID: 34129336


10 p, 4.8 MB

The record appears in these collections:
Research literature > UAB research groups literature > Research Centres and Groups (research output) > Health sciences and biosciences > Institut de Biotecnologia i de Biomedicina (IBB)
Research literature > UAB research groups literature > Research Centres and Groups (research output) > Health sciences and biosciences > Institut de Recerca Sant Pau
Articles > Research articles
Articles > Published articles

 Record created 2022-07-14, last modified 2023-11-29



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