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Penetration of Nanobody-Dextran Polymer Conjugates through Tumor Spheroids

Bitsch, Peter ; Baum, Eva S. ; Beltrán Hernández, Irati ; Bitsch, Sebastian Harald ; Harwood, Jakob ; Oliveira, Sabrina ; Kolmar, Harald (2024)
Penetration of Nanobody-Dextran Polymer Conjugates through Tumor Spheroids.
In: Pharmaceutics, 2023, 15 (10)
doi: 10.26083/tuprints-00024648
Article, Secondary publication, Publisher's Version

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Item Type: Article
Type of entry: Secondary publication
Title: Penetration of Nanobody-Dextran Polymer Conjugates through Tumor Spheroids
Language: English
Date: 16 January 2024
Place of Publication: Darmstadt
Year of primary publication: 2023
Place of primary publication: Basel
Publisher: MDPI
Journal or Publication Title: Pharmaceutics
Volume of the journal: 15
Issue Number: 10
Collation: 17 Seiten
DOI: 10.26083/tuprints-00024648
Corresponding Links:
Origin: Secondary publication DeepGreen

Here we report the generation of nanobody dextran polymer conjugates (dextraknobs) that are loaded with small molecules, i.e., fluorophores or photosensitizers, for potential applications in cancer diagnostics and therapy. To this end, the molecules are conjugated to the dextran polymer which is coupled to the C-terminus of an EGFR-specific nanobody using chemoenzymatic approaches. A monovalent EGFR-targeted nanobody and biparatopic version modified with different dextran average molecular weights (1000, 5000, and 10,000) were probed for their ability to penetrate tumor spheroids. For monovalent Cy5-labeled dextraknobs, the utilization of smaller sized dextran (MW 5000 vs. 10,000) was found to be beneficial for more homogeneous penetration into A431 tumor spheroids over time. For the biparatopic dual nanobody comprising MW 1000, 5000, and 10,000 dextran labeled with photosensitizer IRDye700DX, penetration behavior was comparable to that of a direct nanobody-photosensitizer conjugate lacking a dextran scaffold. Additionally, dextraknobs labeled with IRDye700DX incubated with cells in 2D and 3D showed potent cell killing upon illumination, thus inducing photodynamic therapy (PDT). In line with previous results, monovalent nanobody conjugates displayed deeper and more homogenous penetration through spheroids than the bivalent conjugates. Importantly, the smaller size dextrans did not affect the distribution of the conjugates, thus encouraging further development of dextraknobs.

Uncontrolled Keywords: nanobodies, dextran, photosensitizer, tumor spheroid penetration, photodynamic therapy
Status: Publisher's Version
URN: urn:nbn:de:tuda-tuprints-246483
Additional Information:

This article belongs to the Special Issue Photodynamic Therapy in Cancer: Principles, State of the Art, and Future Directions

Classification DDC: 500 Science and mathematics > 540 Chemistry
500 Science and mathematics > 570 Life sciences, biology
600 Technology, medicine, applied sciences > 610 Medicine and health
Divisions: Interdisziplinäre Forschungsprojekte > Centre for Synthetic Biology
07 Department of Chemistry > Clemens-Schöpf-Institut > Fachgebiet Biochemie
Date Deposited: 16 Jan 2024 13:06
Last Modified: 18 Jan 2024 10:11
SWORD Depositor: Deep Green
URI: https://tuprints.ulb.tu-darmstadt.de/id/eprint/24648
PPN: 514759704
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