Transient Multivalent Nanobody Targeting to CD206-Expressing Cells via PH-Degradable Nanogels.

Maximilian Scherger, Evangelia Bolli, Ana Rita Pombo Antunes, Sana Arnouk, Judith Stickdorn, Alexandra Van Driessche, Hansjörg Schild, Stephan Grabbe, Bruno De Geest, Jo Van Ginderachter, Lutz Nuhn

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

To target nanomedicines to specific cells, especially of the immune system, nanobodies can be considered as an attractive tool, as they lack the Fc part as compared to traditional antibodies and, thus, prevent unfavorable Fc-receptor mediated mistargeting. For that purpose, we have site-specifically conjugated CD206/MMR-targeting nanobodies to three types of dye-labeled nanogel derivatives: non-degradable nanogels, acid-degradable nanogels (with ketal crosslinks), and single polymer chains (also obtained after nanogel degradation). All of them can be obtained from the same reactive ester precursor block copolymer. After incubation with naïve or MMR-expressing Chinese hamster ovary (CHO) cells, a nanobody mediated targeting and uptake could be confirmed for the nanobody-modified nanocarriers. Thereby, the intact nanogels that display nanobodies on their surface in a multivalent way showed a much stronger binding and uptake compared to the soluble polymers. Based on their acidic pH-responsive degradation potential, ketal crosslinked nanogels are capable of mediating a transient targeting that gets diminished upon unfolding into single polymer chains after endosomal acidification. Such control over particle integrity and targeting performance can be considered as highly attractive for safe and controllable immunodrug delivery purposes.
Original languageEnglish
Article number2222
Number of pages14
JournalCells
Volume9
Issue number10
DOIs
Publication statusPublished - 1 Oct 2020

Fingerprint

Dive into the research topics of 'Transient Multivalent Nanobody Targeting to CD206-Expressing Cells via PH-Degradable Nanogels.'. Together they form a unique fingerprint.

Cite this