TY - JOUR
T1 - Self-Assembled Nanobodies as Selectively Targeted, Nanostructured, and Multivalent Materials
AU - Sánchez-García, Laura
AU - Voltà-Durán, Eric
AU - Parladé, Eloi
AU - Mazzega, Elisa
AU - Sánchez-Chardi, Alejandro
AU - Serna, Naroa
AU - López-Laguna, Hèctor
AU - Mitstorfer, Mara
AU - Unzueta, Ugutz
AU - Vázquez, Esther
AU - Villaverde, Antonio
AU - De Marco, Ario
N1 - Publisher Copyright:
© 2021 American Chemical Society.
PY - 2021/6/30
Y1 - 2021/6/30
N2 - 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.
AB - 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.
KW - biomaterials
KW - controlled delivery
KW - nanobodies
KW - nanoparticles
KW - ricin
KW - self-assembling
UR - http://www.scopus.com/inward/record.url?scp=85110233812&partnerID=8YFLogxK
U2 - 10.1021/acsami.1c08092
DO - 10.1021/acsami.1c08092
M3 - Article
C2 - 34129336
AN - SCOPUS:85110233812
SN - 1944-8244
VL - 13
SP - 29406
EP - 29415
JO - ACS applied materials & interfaces
JF - ACS applied materials & interfaces
IS - 25
ER -