Multifunctional antibody-conjugated coiled-coil protein nanoparticles for selective cell targeting
Gil Garcia, Marcos (Universitat Autònoma de Barcelona. Institut de Biotecnologia i de Biomedicina "Vicent Villar Palasí")
Ventura, Salvador (Departament de Bioquímica i de Biologia Molecular)

Data:	2021
Resum:	Nanostructures decorated with antibodies (Abs) are applied in bioimaging and therapeutics. However, most covalent conjugation strategies affect Abs functionality. In this study, we aimed to create protein-based nanoparticles to which intact Abs can be attached through tight, specific, and noncovalent interactions. Initially considered waste products, bacterial inclusion bodies (IBs) have been used in biotechnology and biomedicine. However, the amyloid-like nature of IBs limits their functionality and raises safety concerns. To bypass these obstacles, we have recently developed highly functional α-helix-rich IBs exploiting the natural self-assembly capacity of coiled-coil domains. We used this approach to create spherical, submicrometric, biocompatible and fluorescent protein nanoparticles capable of capturing Abs with high affinity. We showed that these IBs can be exploited for Ab-directed cell targeting. Simultaneous decoration of the nanoparticles with two different Abs in a controllable ratio enabled the construction of a bispecific antibody mimic that redirected T lymphocytes specifically to cancer cells. Overall, we describe an easy and cost-effective strategy to produce multivalent, traceable protein nanostructures with the potential to be used for biomedical applications. Statement of significance: Functional inclusion bodies (IBs) are promising platforms for biomedical and biotechnological applications. These nanoparticles are usually sustained by amyloid-like interactions, which imposes some limitations on their use. In this work, we exploit the natural coiled-coil self-assembly properties to create highly functional, nonamyloid, and fluorescent IBs capable of capturing antibodies. These protein-based nanoparticles are successfully used to specifically and simultaneously target two unrelated cell types and bring them close together, becoming a technology with potential application in bioimaging and immunotherapy.
Ajuts:	Ministerio de Economía y Competitividad BIO2016-78,310-R Ministerio de Ciencia e Innovación PID2019-105017RB-I00 Ministerio de Ciencia e Innovación FPU16/02465
Nota:	Altres ajuts: ICREA-Academia 2015 and 2020
Nota:	Altres ajuts: acords transformatius de la UAB
Drets:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, i la comunicació pública de l'obra, sempre que no sigui amb finalitats comercials, i sempre que es reconegui l'autoria de l'obra original. No es permet la creació d'obres derivades.
Llengua:	Anglès
Document:	Article ; recerca ; Versió publicada
Matèria:	Functional inclusion bodies ; Coiled-coil ; Protein nanoparticles ; Antibody ; Cell targeting
Publicat a:	Acta Biomaterialia, Vol. 131 (September 2021) , p. 472-482, ISSN 1878-7568

DOI: 10.1016/j.actbio.2021.06.040
PMID: 34192568

11 p, 2.4 MB

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