date: 2020-10-01T09:30:16Z
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pdf:docinfo:title: Transient Multivalent Nanobody Targeting to CD206-Expressing Cells via PH-Degradable Nanogels
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subject: 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.
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dc:title: Transient Multivalent Nanobody Targeting to CD206-Expressing Cells via PH-Degradable Nanogels
modified: 2020-10-01T09:30:16Z
cp:subject: 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.
pdf:docinfo:subject: 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.
pdf:docinfo:creator: Maximilian Scherger, Evangelia Bolli, Ana Rita Pombo Antunes, Sana Arnouk, Judith Stickdorn, Alexandra Van Driessche, Hansjörg Schild, Stephan Grabbe, Bruno G. De Geest, Jo A. Van Ginderachter and Lutz Nuhn
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meta:author: Maximilian Scherger, Evangelia Bolli, Ana Rita Pombo Antunes, Sana Arnouk, Judith Stickdorn, Alexandra Van Driessche, Hansjörg Schild, Stephan Grabbe, Bruno G. De Geest, Jo A. Van Ginderachter and Lutz Nuhn
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Creation-Date: 2020-10-01T09:30:16Z
Author: Maximilian Scherger, Evangelia Bolli, Ana Rita Pombo Antunes, Sana Arnouk, Judith Stickdorn, Alexandra Van Driessche, Hansjörg Schild, Stephan Grabbe, Bruno G. De Geest, Jo A. Van Ginderachter and Lutz Nuhn
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Keywords: nanogel; nanobody; targeting; RAFT polymerization; click chemistry; CD206; TAM; M2 macrophage; multivalency; targeting
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dc:creator: Maximilian Scherger, Evangelia Bolli, Ana Rita Pombo Antunes, Sana Arnouk, Judith Stickdorn, Alexandra Van Driessche, Hansjörg Schild, Stephan Grabbe, Bruno G. De Geest, Jo A. Van Ginderachter and Lutz Nuhn
dcterms:created: 2020-10-01T09:30:16Z
Last-Modified: 2020-10-01T09:30:16Z
dcterms:modified: 2020-10-01T09:30:16Z
title: Transient Multivalent Nanobody Targeting to CD206-Expressing Cells via PH-Degradable Nanogels
Last-Save-Date: 2020-10-01T09:30:16Z
pdf:docinfo:keywords: nanogel; nanobody; targeting; RAFT polymerization; click chemistry; CD206; TAM; M2 macrophage; multivalency; targeting
pdf:docinfo:modified: 2020-10-01T09:30:16Z
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creator: Maximilian Scherger, Evangelia Bolli, Ana Rita Pombo Antunes, Sana Arnouk, Judith Stickdorn, Alexandra Van Driessche, Hansjörg Schild, Stephan Grabbe, Bruno G. De Geest, Jo A. Van Ginderachter and Lutz Nuhn
dc:subject: nanogel; nanobody; targeting; RAFT polymerization; click chemistry; CD206; TAM; M2 macrophage; multivalency; targeting
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meta:keyword: nanogel; nanobody; targeting; RAFT polymerization; click chemistry; CD206; TAM; M2 macrophage; multivalency; targeting
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pdf:docinfo:created: 2020-10-01T09:30:16Z