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

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

doi:10.3390/cells9102222

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

Maximilian Scherger

^1,†,

Evangelia Bolli

^2,3,†,

Ana Rita Pombo Antunes

^2,3,

Sana Arnouk

^2,3,

Judith Stickdorn

¹,

Alexandra Van Driessche

⁴,

Hansjörg Schild

⁵,

Stephan Grabbe

⁶

Bruno G. De Geest

⁴,

Jo A. Van Ginderachter

^2,3,*

and

Lutz Nuhn

^1,*

Max Planck Institute for Polymer Research, Ackermannweg 10, 55128 Mainz, Germany

Myeloid Cell Immunology Lab, VIB Center for Inflammation Research, Pleinlaan 2, 1050 Brussels, Belgium

Lab of Cellular and Molecular Immunology, Vrije Universiteit Brussel, Pleinlaan 2, 1050 Brussels, Belgium

⁴

Department of Pharmaceutics, Ghent University, Ottergemsesteenweg 460, 9000 Ghent, Belgium

⁵

Institute of Immunology, University Medical Center of Johannes Gutenberg-University Mainz, Obere Zahlbacher Straße 63, 55131 Mainz, Germany

⁶

Department of Dermatology, University Medical Center of Johannes Gutenberg-University Mainz, Obere Zahlbacher Straße 63, 55131 Mainz, Germany

Authors to whom correspondence should be addressed.

^†

These authors contributed equally to this paper.

Cells 2020, 9(10), 2222; https://doi.org/10.3390/cells9102222

Received: 2 September 2020 / Revised: 23 September 2020 / Accepted: 27 September 2020 / Published: 1 October 2020

(This article belongs to the Special Issue Nanoparticles in Cancer Immunotherapy)

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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. View Full-Text

Keywords: nanogel; nanobody; targeting; RAFT polymerization; click chemistry; CD206; TAM; M2 macrophage; multivalency; targeting

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MDPI and ACS Style

Scherger, M.; Bolli, E.; Antunes, A.R.P.; Arnouk, S.; Stickdorn, J.; Van Driessche, A.; Schild, H.; Grabbe, S.; De Geest, B.G.; Van Ginderachter, J.A.; Nuhn, L. Transient Multivalent Nanobody Targeting to CD206-Expressing Cells via PH-Degradable Nanogels. Cells 2020, 9, 2222. https://doi.org/10.3390/cells9102222

AMA Style

Scherger M, Bolli E, Antunes ARP, Arnouk S, Stickdorn J, Van Driessche A, Schild H, Grabbe S, De Geest BG, Van Ginderachter JA, Nuhn L. Transient Multivalent Nanobody Targeting to CD206-Expressing Cells via PH-Degradable Nanogels. Cells. 2020; 9(10):2222. https://doi.org/10.3390/cells9102222

Chicago/Turabian Style

Scherger, Maximilian, Evangelia Bolli, Ana R.P. Antunes, Sana Arnouk, Judith Stickdorn, Alexandra Van Driessche, Hansjörg Schild, Stephan Grabbe, Bruno G. De Geest, Jo A. Van Ginderachter, and Lutz Nuhn. 2020. "Transient Multivalent Nanobody Targeting to CD206-Expressing Cells via PH-Degradable Nanogels" Cells 9, no. 10: 2222. https://doi.org/10.3390/cells9102222

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