AGuIX nanoparticle-nanobody bioconjugates to target immune checkpoint receptors

• Published in: Nanoscale 2024-02, Vol.16 (5), p.2347-236
• Main Authors: Carmès, Léna, Bort, Guillaume, Lux, François, Seban, Léa, Rocchi, Paul, Muradova, Zeinaf, Hagège, Agnès, Heinrich-Balard, Laurence, Delolme, Frédéric, Gueguen-Chaignon, Virginie, Truillet, Charles, Crowley, Stephanie, Bello, Elisa, Doussineau, Tristan, Dougan, Michael, Tillement, Olivier, Schoenfeld, Jonathan D, Brown, Needa, Berbeco, Ross
• Format: Article
• Language: English
• Subjects: Cancer; Chemical Sciences; Chemical synthesis; Conjugation; Life Sciences; Nanoparticles; Radiation therapy; Tumors
• ISSN: 2040-3364; 2040-3372
• DOI: 10.1039/d3nr04777f

This article presents bioconjugates combining nanoparticles (AGuIX) with nanobodies (VHH) targeting Programmed Death-Ligand 1 (PD-L1, A12 VHH) and Cluster of Differentiation 47 (CD47, A4 VHH) for active tumor targeting. AGuIX nanoparticles offer theranostic capabilities and an efficient biodistribution/pharmacokinetic profile (BD/PK), while VHH's reduced size (15 kDa) allows efficient tumor penetration. Site-selective sortagging and click chemistry were compared for bioconjugation. While both methods yielded bioconjugates with similar functionality, click chemistry demonstrated higher yield and could be used for the conjugation of various VHH. The specific targeting of AGuIX@VHH has been demonstrated in both in vitro and ex vivo settings, paving the way for combined targeted immunotherapies, radiotherapy, and cancer imaging. Comparison of click chemistry and sortagging grafting strategies for functionalizing AGuIX nanoparticles with nanobodies to develop a tri-functional technology combining MRI imaging, radiotherapy, and immunotherapy by inhibiting immune checkpoints.