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Selectivity in Bone Targeting with Multivalent Dendritic Polyanion Dye Conjugates
Author(s) -
Gröger Dominic,
Kerschnitzki Michael,
Weinhart Marie,
Reimann Sabine,
Schneider Tobias,
Kohl Benjamin,
Wagermaier Wolfgang,
SchulzeTanzil Gundula,
Fratzl Peter,
Haag Rainer
Publication year - 2014
Publication title -
advanced healthcare materials
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.288
H-Index - 90
eISSN - 2192-2659
pISSN - 2192-2640
DOI - 10.1002/adhm.201300205
Subject(s) - bisphosphonate , chemistry , conjugate , dendrimer , phosphonate , sulfonate , cytotoxicity , combinatorial chemistry , biochemistry , in vitro , organic chemistry , mathematical analysis , osteoporosis , mathematics , endocrinology , sodium , medicine
Targeting bone with anionic macromolecules is a potent approach for the development of novel diagnostics and therapeutics for bone related diseases. A highly efficient modular synthesis of dendritic polyglycerol (dPG) polyanion dye conjugates, namely, sulfates, sulfonates, carboxylates, phosphates, phosphonates, and bisphosphonates via click chemistry is presented. By investigating the microarchitecture of stained bone sections with confocal laser scanning microscopy, the bisphosphonate, phosphonate, and phosphate functionalized polymers are identified as strongly penetrating compounds, whereas sulfates, sulfonates, and carboxylates reveal a weaker binding to hydroxyapatite (HA) but a more pronounced affinity toward collagen. In a quantitative HA binding assay, the affinity of the dPG sulfonate, sulfate, and carboxylate toward collagen and the exceptional high HA affinity of the phosphorous containing polyelectrolytes are validated. This shows the potential of dendritic polyphosphates and phosphonates as alternatives to the commonly employed bisphosphonate modification. In cytotoxicity studies with murine fibroblasts, the conjugates have no significant effect on the cell viability at 10 ‐5 m . All polyanions are taken up into the cells within 24 h. The presented synthetic approach allows versatile extensions for preparing conjugates for selective bone imaging applications, tissue engineering, and drug delivery.