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

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 requ...

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Detalles Bibliográficos
Autores: Wang, Weiqiang|||0000-0002-6962-8811, Gil-Garcia, Marcos|||0000-0002-7457-7860, Ventura, Salvador|||0000-0002-9652-6351
Tipo de recurso: artículo
Fecha de publicación:2021
País:España
Institución:Universitat Autònoma de Barcelona
Repositorio:Dipòsit Digital de Documents de la UAB
Idioma:inglés
OAI Identifier:oai:ddd.uab.cat:263094
Acceso en línea:https://ddd.uab.cat/record/263094
https://dx.doi.org/urn:doi:10.1021/acsami.0c21996
Access Level:acceso abierto
Palabra clave:Amyloid
Dual- or multitargeting
Multivalency
Antibody
Nanorods
Nanomaterials
Descripción
Sumario: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.