Legomedicine - a versatile chemo-enzymatic approach for the preparation of targeted dual-labeled llama antibody-nanoparticle conjugates

S.A.M. van Lith, S.M.J. van Duijnhoven, A.C. Navis, W.P.J. Leenders, E. Dolk, J.W.H. Wennink, C.F. Nostrum, van, J.C.M. van Hest

Research output: Contribution to journalArticleAcademicpeer-review

27 Citations (Scopus)
151 Downloads (Pure)

Abstract

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.

Original languageEnglish
Pages (from-to)539-548
Number of pages10
JournalBioconjugate Chemistry
Volume28
Issue number2
DOIs
Publication statusPublished - 15 Feb 2017

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