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
Artikel, Zweitveröffentlichung, Verlagsversion
 | Es ist eine neuere Version dieses Eintrags verfügbar. |
Kurzbeschreibung (Abstract)
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.
| Typ des Eintrags: | Artikel |
|---|---|
| Erschienen: | 2024 |
| Autor(en): | Bitsch, Peter ; Baum, Eva S. ; Beltrán Hernández, Irati ; Bitsch, Sebastian Harald ; Harwood, Jakob ; Oliveira, Sabrina ; Kolmar, Harald |
| Art des Eintrags: | Zweitveröffentlichung |
| Titel: | Penetration of Nanobody-Dextran Polymer Conjugates through Tumor Spheroids |
| Sprache: | Englisch |
| Publikationsjahr: | 16 Januar 2024 |
| Ort: | Darmstadt |
| Publikationsdatum der Erstveröffentlichung: | 2023 |
| Ort der Erstveröffentlichung: | Basel |
| Verlag: | MDPI |
| Titel der Zeitschrift, Zeitung oder Schriftenreihe: | Pharmaceutics |
| Jahrgang/Volume einer Zeitschrift: | 15 |
| (Heft-)Nummer: | 10 |
| Kollation: | 17 Seiten |
| DOI: | 10.26083/tuprints-00024648 |
| URL / URN: | https://tuprints.ulb.tu-darmstadt.de/24648 |
| Zugehörige Links: | |
| Herkunft: | Zweitveröffentlichung DeepGreen |
| Kurzbeschreibung (Abstract): | 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. |
| Freie Schlagworte: | nanobodies, dextran, photosensitizer, tumor spheroid penetration, photodynamic therapy |
| Status: | Verlagsversion |
| URN: | urn:nbn:de:tuda-tuprints-246483 |
| Zusätzliche Informationen: | This article belongs to the Special Issue Photodynamic Therapy in Cancer: Principles, State of the Art, and Future Directions |
| Sachgruppe der Dewey Dezimalklassifikatin (DDC): | 500 Naturwissenschaften und Mathematik > 540 Chemie 500 Naturwissenschaften und Mathematik > 570 Biowissenschaften, Biologie 600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin, Gesundheit |
| Fachbereich(e)/-gebiet(e): | Interdisziplinäre Forschungsprojekte Interdisziplinäre Forschungsprojekte > Centre for Synthetic Biology 07 Fachbereich Chemie 07 Fachbereich Chemie > Clemens-Schöpf-Institut > Fachgebiet Biochemie |
| Hinterlegungsdatum: | 16 Jan 2024 13:06 |
| Letzte Änderung: | 17 Jan 2024 09:10 |
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| Suche nach Titel in: | TUfind oder in Google |
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