Legomedicine - a versatile chemo-enzymatic approach for the preparation of targeted dual-labeled llama antibody-nanoparticle conjugates
Articlevan Lith, S.A.M., van Duijnhoven, S.M.J., Navis, A.C., Leenders, W.P.J., Dolk, E., Wennink, J.W.H., Nostrum, van, C.F. & van Hest, J.C.M. (2017). Legomedicine - a versatile chemo-enzymatic approach for the preparation of targeted dual-labeled llama antibody-nanoparticle conjugates. Bioconjugate Chemistry, 28(2), 539-548. In Scopus Cited 7 times.
Conjugation of llama single domain antibody fragments (Variable Heavy chain domains of Heavy chain antibodies, VHHs) to diagnostic or therapeutic nanoparticles, peptides, proteins, or drugs offers many opportunities for optimized targeted cancer treatment. Currently, mostly nonspecific conjugation strategies or genetic fusions are used that may compromise VHH functionality. In this paper we present a versatile modular approach for bioorthogonal VHH modification and conjugation. First, sortase A mediated transPEGylation is used for introduction of a chemical click moiety. The resulting clickable VHHs are then used for conjugation to other groups employing the Cu+-independent strain-promoted alkyne-azide cycloadition (SPAAC) reaction. Using this approach, tail-to-tail bispecific VHHs and VHH-targeted nanoparticles are generated without affecting VHH functionality. Furthermore, this approach allows the bioconjugation of multiple moieties to VHHs for simple and convenient production of VHH-based theranostics.