Self-Assembled Nanobodies as Selectively Targeted, Nanostructured, and Multivalent Materials

Nanobodies represent valuable tools in advanced therapeutic strategies but their small size (similar to 2.5 x similar to 4 nm) and limited valence for interactions might pose restrictions for in vivo applications, especially regarding their modest capacity for multivalent and cooperative interaction...

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Autores: Sanchez-Garcia, L, Volta-Duran, E, Parlade, E, Mazzega, E, Sanchez-Chardi, A, Serna, N, Lopez-Laguna, H, Mitstorfer, M, Unzueta, U, Vazquez, E, Villaverde, A, de Marco, A
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2021
País:España
Institución:Institut d’Investigació Biomèdica Sant Pau (IIB Sant Pau)
Repositorio:r-IIB SANT PAU. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica Sant Pau
OAI Identifier:oai:iibsantpau.fundanetsuite.com:p4593
Acceso en línea:https://iibsantpau.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=4593
Access Level:acceso abierto
Palabra clave:nanobodies
self-assembling
ricin
nanoparticles
controlled delivery
biomaterials
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spelling Self-Assembled Nanobodies as Selectively Targeted, Nanostructured, and Multivalent MaterialsSanchez-Garcia, LVolta-Duran, EParlade, EMazzega, ESanchez-Chardi, ASerna, NLopez-Laguna, HMitstorfer, MUnzueta, UVazquez, EVillaverde, Ade Marco, Ananobodiesself-assemblingricinnanoparticlescontrolled deliverybiomaterialsNanobodies represent valuable tools in advanced therapeutic strategies but their small size (similar to 2.5 x similar to 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.AMER CHEMICAL SOC2021info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttps://iibsantpau.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=4593ACS Applied Materials & InterfacesISSN: 19448244ISSNe: 19448252reponame:r-IIB SANT PAU. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica Sant Pauinstname:Institut d’Investigació Biomèdica Sant Pau (IIB Sant Pau)Inglésinfo:eu-repo/semantics/openAccessoai:iibsantpau.fundanetsuite.com:p45932026-06-14T12:41:47Z
dc.title.none.fl_str_mv Self-Assembled Nanobodies as Selectively Targeted, Nanostructured, and Multivalent Materials
title Self-Assembled Nanobodies as Selectively Targeted, Nanostructured, and Multivalent Materials
spellingShingle Self-Assembled Nanobodies as Selectively Targeted, Nanostructured, and Multivalent Materials
Sanchez-Garcia, L
nanobodies
self-assembling
ricin
nanoparticles
controlled delivery
biomaterials
title_short Self-Assembled Nanobodies as Selectively Targeted, Nanostructured, and Multivalent Materials
title_full Self-Assembled Nanobodies as Selectively Targeted, Nanostructured, and Multivalent Materials
title_fullStr Self-Assembled Nanobodies as Selectively Targeted, Nanostructured, and Multivalent Materials
title_full_unstemmed Self-Assembled Nanobodies as Selectively Targeted, Nanostructured, and Multivalent Materials
title_sort Self-Assembled Nanobodies as Selectively Targeted, Nanostructured, and Multivalent Materials
dc.creator.none.fl_str_mv Sanchez-Garcia, L
Volta-Duran, E
Parlade, E
Mazzega, E
Sanchez-Chardi, A
Serna, N
Lopez-Laguna, H
Mitstorfer, M
Unzueta, U
Vazquez, E
Villaverde, A
de Marco, A
author Sanchez-Garcia, L
author_facet Sanchez-Garcia, L
Volta-Duran, E
Parlade, E
Mazzega, E
Sanchez-Chardi, A
Serna, N
Lopez-Laguna, H
Mitstorfer, M
Unzueta, U
Vazquez, E
Villaverde, A
de Marco, A
author_role author
author2 Volta-Duran, E
Parlade, E
Mazzega, E
Sanchez-Chardi, A
Serna, N
Lopez-Laguna, H
Mitstorfer, M
Unzueta, U
Vazquez, E
Villaverde, A
de Marco, A
author2_role author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv nanobodies
self-assembling
ricin
nanoparticles
controlled delivery
biomaterials
topic nanobodies
self-assembling
ricin
nanoparticles
controlled delivery
biomaterials
description Nanobodies represent valuable tools in advanced therapeutic strategies but their small size (similar to 2.5 x similar to 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.
publishDate 2021
dc.date.none.fl_str_mv 2021
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://iibsantpau.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=4593
url https://iibsantpau.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=4593
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv AMER CHEMICAL SOC
publisher.none.fl_str_mv AMER CHEMICAL SOC
dc.source.none.fl_str_mv ACS Applied Materials & Interfaces
ISSN: 19448244
ISSNe: 19448252
reponame:r-IIB SANT PAU. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica Sant Pau
instname:Institut d’Investigació Biomèdica Sant Pau (IIB Sant Pau)
instname_str Institut d’Investigació Biomèdica Sant Pau (IIB Sant Pau)
reponame_str r-IIB SANT PAU. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica Sant Pau
collection r-IIB SANT PAU. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica Sant Pau
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15.812455

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