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Pàgina inicial > Articles > Articles publicats > Self-assembled nanobodies as selectively targeted, nanostructured, and multivalent materials |
Data: | 2021 |
Resum: | 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. |
Ajuts: | 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 |
Nota: | Altres ajuts: acords transformatius de la UAB |
Nota: | Altres ajuts: EU COST Action CA 17140 ; ICREA Academia award |
Drets: | 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. |
Llengua: | Anglès |
Document: | Article ; recerca ; Versió publicada |
Matèria: | Nanobodies ; Self-assembling ; Ricin ; Nanoparticles ; Controlled delivery ; Biomaterials |
Publicat a: | ACS applied materials & interfaces, Vol. 13, Issue 25 (June 2021) , p. 29406-29415, ISSN 1944-8252 |
10 p, 4.8 MB |