Details
| Originalsprache | Englisch |
|---|---|
| Seiten (von - bis) | 375-385 |
| Seitenumfang | 11 |
| Fachzeitschrift | Advanced healthcare materials |
| Jahrgang | 3 |
| Ausgabenummer | 3 |
| Frühes Online-Datum | 29 Aug. 2013 |
| Publikationsstatus | Veröffentlicht - März 2014 |
| Extern publiziert | Ja |
Abstract
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 10-5m. 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.
ASJC Scopus Sachgebiete
- Werkstoffwissenschaften (insg.)
- Biomaterialien
- Ingenieurwesen (insg.)
- Biomedizintechnik
- Pharmakologie, Toxikologie und Pharmazie (insg.)
- Pharmazeutische Wissenschaften
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in: Advanced healthcare materials, Jahrgang 3, Nr. 3, 03.2014, S. 375-385.
Publikation: Beitrag in Fachzeitschrift › Artikel › Forschung › Peer-Review
}
TY - JOUR
T1 - Selectivity in Bone Targeting with Multivalent Dendritic Polyanion Dye Conjugates
AU - Gröger, Dominic
AU - Kerschnitzki, Michael
AU - Weinhart, Marie
AU - Reimann, Sabine
AU - Schneider, Tobias
AU - Kohl, Benjamin
AU - Wagermaier, Wolfgang
AU - Schulze-Tanzil, Gundula
AU - Fratzl, Peter
AU - Haag, Rainer
PY - 2014/3
Y1 - 2014/3
N2 - 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 10-5m. 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.
AB - 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 10-5m. 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.
KW - Bisphosphonates
KW - Bone targeting
KW - Conjugates
KW - Hydroxyapatite
KW - Inflammation
UR - http://www.scopus.com/inward/record.url?scp=84895494201&partnerID=8YFLogxK
U2 - 10.1002/adhm.201300205
DO - 10.1002/adhm.201300205
M3 - Article
C2 - 23996966
AN - SCOPUS:84895494201
VL - 3
SP - 375
EP - 385
JO - Advanced healthcare materials
JF - Advanced healthcare materials
SN - 2192-2640
IS - 3
ER -