ECTS2014 Poster Presentations Chondrocytes and cartilage (9 abstracts)
Selective targeting of bone and cartilage with multivalent dendritic polyanions
Sabine Reimann 1 , Dominic Gröger 1 , Ngee Han Lim 2 , Kai Licha 3 , Pia Welker 3 , Tobias Schneider 4 , Hideaki Nagase 2 , Peter Fratzl 5 & Rainer Haag 1
1Institute of Chemistry and Biochemistry, Freie Universität Berlin, Berlin, Germany; 2Kennedy Institute of Rheumatology Division, Faculty of Medicine, Imperial College London, London, UK; 3Charite-Universitätsmedizin Berlin, CBF, Zentralinstitut für Laboratoriumsmedizin und Pathobiochemie, Berlin, Germany; 4Charité-Universitätsmedizin Berlin CBF, Klinik für Orthopädische Unfall- und Wiederherstellungschirurgie, Berlin, Germany; 5Max Planck Institute of Colloids and Interfaces Department of Biomaterials, Potsdam, Germany.
Background and objective: Targeting bone and cartilage includes approaches using tetracyclines, peptide conjugates, as well as anionic moieties like bisphosphonates. However, the selective targeting of the different compartments still remains a challenge. In previous studies native and demineralized ovine bone was used to analyze the affinity of polyanions derived from dendritic polyglycerol (dPG) toward hydroxyapatite and collagen. Whereas the neutral polymer did not show any interaction with bone, a selective binding to hydroxyapatite and collagen was observed depending on the anionic moiety of the polymer. Based on these results the binding affinity of polyanions toward cartilage was investigated to obtain selective targeting agents.
Results: Interleukin-1 (IL-1) treated porcine cartilage explants were incubated with dye-labled dPG anions containing phosphates (dPGP), bisphosphonates (dPGBP), and sulfates (dPGS) to investigate their binding affinity by fluorescence imaging showing dPGS to efficiently penetrate the cartilage tissue, able to accumulate in chondrocytes. The non-labeled polyanions were used to determine the inhibition of IL-1 stimulated glycosaminoglycan release finding dPGS to reduce the release. Compared to this, the neutral polymer did not show any interaction with cartilage. In a collagen-induced rheumatoid arthritis rat model the polymers were investigated regarding their accumulation in inflamed joints in vivo using near infrared optical imaging. Both dPGBP and dPGS were found to posess an enhanced affinity to inflamed tissue with dPGS showing a higher binding affinity to inflamed cartilage as investigated by histological examinations. Moreover, dPGBP was also found in calcified areas in healthy joints in contrast to dPGS.
Conclusion: Dendritic polyglycerol based anions were found to be promising candidates for diagnostic and therapeutic applications to target bone and cartilage indicating a high selectivity toward these tissues.
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Bone Abstracts
ISSN 2052-1219 (online)
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