4.8 Article

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

期刊

ACS APPLIED MATERIALS & INTERFACES
卷 13, 期 25, 页码 29406-29415

出版社

AMER CHEMICAL SOC
DOI: 10.1021/acsami.1c08092

关键词

nanobodies; self-assembling; ricin; nanoparticles; controlled delivery; biomaterials

资金

  1. Agencia Estatal de Investigacion (AEI)
  2. Fondo Europeo de Desarrollo Regional (FEDER) [BIO2016-76063-R]
  3. AGAUR [2019FI_B00352, 2018FI_B2_00051, 2017SGR-229]
  4. CIBER-BBN (project NANOPROTHER)
  5. Javna Agencija za Raziskovalno dejavnost Republike Slovenije [ARRS/N4-0046, ARRS/J-9322]
  6. EU COST Action [CA 17140]
  7. Ministerio de Ciencia, Innovacion y Universidades [FPU18/0461]
  8. ISCIII [CP19/00028]
  9. European Social Fund
  10. ICREA ACADEMIA award

向作者/读者索取更多资源

Nanobodies are valuable tools in advanced therapeutic strategies, but their small size and limited valence for interactions may pose restrictions for in vivo applications. Modular protein constructs have been designed to fuse nanobodies with protein domains, promoting self-assembly into stable nanoparticles with maintained specificity for targets.
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.

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