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  Dendritic polyglycerol anions for the selective targeting of native and inflamed articular cartilage

Reimann, S., Schneider, T., Welker, P., Neumann, F., Licha, K., Schulze-Tanzil, G., et al. (2017). Dendritic polyglycerol anions for the selective targeting of native and inflamed articular cartilage. Journal of Materials Chemistry B, 5, 4754-4767. doi:10.1039/C7TB00618G.

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 Urheber:
Reimann, Sabine, Autor
Schneider, Tobias, Autor
Welker, Pia, Autor
Neumann, Falko, Autor
Licha, Kai, Autor
Schulze-Tanzil, Gundula, Autor
Wagermaier, Wolfgang1, Autor           
Fratzl, Peter2, Autor           
Haag, Rainer, Autor
Affiliations:
1Wolfgang Wagermaier, Biomaterialien, Max Planck Institute of Colloids and Interfaces, Max Planck Society, ou_1863296              
2Peter Fratzl, Biomaterialien, Max Planck Institute of Colloids and Interfaces, Max Planck Society, ou_1863294              

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Schlagwörter: Open Access
 Zusammenfassung: The destruction of articular cartilage is a critical feature in joint diseases. An approach to selectively target the damaged tissue is promising for the development of diagnostic and therapeutic agents. We herein present the interaction of dendritic polyglycerol (dPG) anions with native and inflamed cartilage. Confocal laser scanning microscopy revealed the inert character of dPG and low functionalized dPG bisphosphonate (dPGBP7%) toward cartilage in vitro. An enhanced binding was observed for highly functionalized dPG bisphosphonate, sulfate, and phosphate, which additionally showed a higher affinity to IL-1β treated tissue. The mixed anion containing sulfate and bisphosphonate groups exhibited an exceptionally high affinity to cartilage and strongly bound to collagen type II, as shown by a normalized fluorescence-based binding assay. All polyglycerol anions, except dPGBP7%, were taken up by chondrocytes within 24 h and no cytotoxicity was found up to 10−5 M. In a rheumatoid arthritis model, dPGBP7% accumulated in mineralized compartments of inflamed joints and showed an increasing affinity to cartilage with higher clinical scores, as evident from histological examinations. For dPGS no interaction with bone but a strong binding to cartilage, independent of the score, was demonstrated. These results make dPG anions promising candidates for the selective targeting of cartilage tissue.

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 Datum: 2017-05-262017
 Publikationsstatus: Erschienen
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 Identifikatoren: DOI: 10.1039/C7TB00618G
BibTex Citekey: C7TB00618G
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Titel: Journal of Materials Chemistry B
Genre der Quelle: Zeitschrift
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Ort, Verlag, Ausgabe: Cambridge, UK : Royal Society of Chemistry
Seiten: - Band / Heft: 5 Artikelnummer: - Start- / Endseite: 4754 - 4767 Identifikator: ISSN: 2050-750X