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Issue 24, 2017
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Dendritic polyglycerol anions for the selective targeting of native and inflamed articular cartilage

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Abstract

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.

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

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Publication details

The article was received on 06 Mar 2017, accepted on 17 May 2017 and first published on 26 May 2017


Article type: Paper
DOI: 10.1039/C7TB00618G
Citation: J. Mater. Chem. B, 2017,5, 4754-4767
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    Dendritic polyglycerol anions for the selective targeting of native and inflamed articular cartilage

    S. Reimann, T. Schneider, P. Welker, F. Neumann, K. Licha, G. Schulze-Tanzil, W. Wagermaier, P. Fratzl and R. Haag, J. Mater. Chem. B, 2017, 5, 4754
    DOI: 10.1039/C7TB00618G

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