Selectivity in bone targeting with multivalent dendritic polyanion dye conjugates.

Targeting bone with anionic macromolecules is a potent approach for the development of novel diagnostics and therapeutics for bone related diseases. A highly effi cient 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 identifi ed as strongly penetrating compounds, whereas sulfates, sulfonates, and carboxylates reveal a weaker binding to hydroxyapatite (HA) but a more pronounced affi nity toward collagen. In a quantitative HA binding assay, the affi nity of the dPG sulfonate, sulfate, and carboxylate toward collagen and the exceptional high HA affi nity of the phosphorous containing polyelectrolytes are validated. This shows the potential of dendritic polyphosphates and phosphonates as alternatives to the commonly employed bisphosphonate modifi cation. In cytotoxicity studies with murine fi broblasts, the conjugates have no signifi cant 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.