Cargando…

Dual Antibody-Conjugated Amyloid Nanorods to Promote Selective Cell–Cell Interactions

[Image: see text] Grafting biomolecules on nanostructures’ surfaces is an increasingly used strategy to target pathogenic cells, with both diagnostic and therapeutic applications. However, nanomaterials monofunctionalized by conjugating a single type of ligand find limited uses in pathologies/therap...

Descripción completa

Detalles Bibliográficos
Autores principales: Wang, Weiqiang, Gil-Garcia, Marcos, Ventura, Salvador
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Chemical Society 2021
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9262253/
https://www.ncbi.nlm.nih.gov/pubmed/33759489
http://dx.doi.org/10.1021/acsami.0c21996
_version_ 1784742453121646592
author Wang, Weiqiang
Gil-Garcia, Marcos
Ventura, Salvador
author_facet Wang, Weiqiang
Gil-Garcia, Marcos
Ventura, Salvador
author_sort Wang, Weiqiang
collection PubMed
description [Image: see text] Grafting biomolecules on nanostructures’ surfaces is an increasingly used strategy to target pathogenic cells, with both diagnostic and therapeutic applications. However, nanomaterials monofunctionalized by conjugating a single type of ligand find limited uses in pathologies/therapies that require two or more targets/receptors to be targeted and/or activated with a single molecular entity simultaneously. Therefore, multivalent nanomaterials for dual- or multitargeting are attracting significant interest. This study provides a proof of concept of such nanostructures. We have recently developed a modular methodology that allows obtaining amyloid-based materials decorated with active globular domains. Here, this approach is exploited to generate functional amyloid fibrils displaying antibody capture moieties. A high antibody binding affinity and capacity for the resulting nanofibrils, whose size can be manipulated to obtain homogeneous nanorods with high biocompatibility, are demonstrated. These nanorods are then used for specific antibody-mediated targeting of different cell types. Simultaneous conjugation of these nanorods with different antibodies allows obtaining a mimic of a bispecific antibody that redirects T lymphocytes to tumoral cells, holding high potential for immunotherapy. Overall, the work illustrates a modular and straightforward strategy to obtain preparative quantities of multivalent antibody-functionalized nanomaterials with multitargeting properties without the need for covalent modification.
format Online
Article
Text
id pubmed-9262253
institution National Center for Biotechnology Information
language English
publishDate 2021
publisher American Chemical Society
record_format MEDLINE/PubMed
spelling pubmed-92622532022-07-08 Dual Antibody-Conjugated Amyloid Nanorods to Promote Selective Cell–Cell Interactions Wang, Weiqiang Gil-Garcia, Marcos Ventura, Salvador ACS Appl Mater Interfaces [Image: see text] Grafting biomolecules on nanostructures’ surfaces is an increasingly used strategy to target pathogenic cells, with both diagnostic and therapeutic applications. However, nanomaterials monofunctionalized by conjugating a single type of ligand find limited uses in pathologies/therapies that require two or more targets/receptors to be targeted and/or activated with a single molecular entity simultaneously. Therefore, multivalent nanomaterials for dual- or multitargeting are attracting significant interest. This study provides a proof of concept of such nanostructures. We have recently developed a modular methodology that allows obtaining amyloid-based materials decorated with active globular domains. Here, this approach is exploited to generate functional amyloid fibrils displaying antibody capture moieties. A high antibody binding affinity and capacity for the resulting nanofibrils, whose size can be manipulated to obtain homogeneous nanorods with high biocompatibility, are demonstrated. These nanorods are then used for specific antibody-mediated targeting of different cell types. Simultaneous conjugation of these nanorods with different antibodies allows obtaining a mimic of a bispecific antibody that redirects T lymphocytes to tumoral cells, holding high potential for immunotherapy. Overall, the work illustrates a modular and straightforward strategy to obtain preparative quantities of multivalent antibody-functionalized nanomaterials with multitargeting properties without the need for covalent modification. American Chemical Society 2021-03-24 2021-04-07 /pmc/articles/PMC9262253/ /pubmed/33759489 http://dx.doi.org/10.1021/acsami.0c21996 Text en © 2021 American Chemical Society https://creativecommons.org/licenses/by/4.0/Permits the broadest form of re-use including for commercial purposes, provided that author attribution and integrity are maintained (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Wang, Weiqiang
Gil-Garcia, Marcos
Ventura, Salvador
Dual Antibody-Conjugated Amyloid Nanorods to Promote Selective Cell–Cell Interactions
title Dual Antibody-Conjugated Amyloid Nanorods to Promote Selective Cell–Cell Interactions
title_full Dual Antibody-Conjugated Amyloid Nanorods to Promote Selective Cell–Cell Interactions
title_fullStr Dual Antibody-Conjugated Amyloid Nanorods to Promote Selective Cell–Cell Interactions
title_full_unstemmed Dual Antibody-Conjugated Amyloid Nanorods to Promote Selective Cell–Cell Interactions
title_short Dual Antibody-Conjugated Amyloid Nanorods to Promote Selective Cell–Cell Interactions
title_sort dual antibody-conjugated amyloid nanorods to promote selective cell–cell interactions
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9262253/
https://www.ncbi.nlm.nih.gov/pubmed/33759489
http://dx.doi.org/10.1021/acsami.0c21996
work_keys_str_mv AT wangweiqiang dualantibodyconjugatedamyloidnanorodstopromoteselectivecellcellinteractions
AT gilgarciamarcos dualantibodyconjugatedamyloidnanorodstopromoteselectivecellcellinteractions
AT venturasalvador dualantibodyconjugatedamyloidnanorodstopromoteselectivecellcellinteractions