Selectivity in Bone Targeting with Multivalent Dendritic Polyanion Dye Conjugates

Research output: Contribution to journalArticleResearchpeer review

Authors

  • Dominic Gröger
  • Michael Kerschnitzki
  • Marie Weinhart
  • Sabine Reimann
  • Tobias Schneider
  • Benjamin Kohl
  • Wolfgang Wagermaier
  • Gundula Schulze-Tanzil
  • Peter Fratzl
  • Rainer Haag

External Research Organisations

  • Freie Universität Berlin (FU Berlin)
  • Max Planck Institute of Colloids and Interfaces
  • Charité - Universitätsmedizin Berlin
View graph of relations

Details

Original languageEnglish
Pages (from-to)375-385
Number of pages11
JournalAdvanced healthcare materials
Volume3
Issue number3
Early online date29 Aug 2013
Publication statusPublished - Mar 2014
Externally publishedYes

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.

Keywords

    Bisphosphonates, Bone targeting, Conjugates, Hydroxyapatite, Inflammation

ASJC Scopus subject areas

Cite this

Selectivity in Bone Targeting with Multivalent Dendritic Polyanion Dye Conjugates. / Gröger, Dominic; Kerschnitzki, Michael; Weinhart, Marie et al.
In: Advanced healthcare materials, Vol. 3, No. 3, 03.2014, p. 375-385.

Research output: Contribution to journalArticleResearchpeer review

Gröger, D, Kerschnitzki, M, Weinhart, M, Reimann, S, Schneider, T, Kohl, B, Wagermaier, W, Schulze-Tanzil, G, Fratzl, P & Haag, R 2014, 'Selectivity in Bone Targeting with Multivalent Dendritic Polyanion Dye Conjugates', Advanced healthcare materials, vol. 3, no. 3, pp. 375-385. https://doi.org/10.1002/adhm.201300205
Gröger, D., Kerschnitzki, M., Weinhart, M., Reimann, S., Schneider, T., Kohl, B., Wagermaier, W., Schulze-Tanzil, G., Fratzl, P., & Haag, R. (2014). Selectivity in Bone Targeting with Multivalent Dendritic Polyanion Dye Conjugates. Advanced healthcare materials, 3(3), 375-385. https://doi.org/10.1002/adhm.201300205
Gröger D, Kerschnitzki M, Weinhart M, Reimann S, Schneider T, Kohl B et al. Selectivity in Bone Targeting with Multivalent Dendritic Polyanion Dye Conjugates. Advanced healthcare materials. 2014 Mar;3(3):375-385. Epub 2013 Aug 29. doi: 10.1002/adhm.201300205
Gröger, Dominic ; Kerschnitzki, Michael ; Weinhart, Marie et al. / Selectivity in Bone Targeting with Multivalent Dendritic Polyanion Dye Conjugates. In: Advanced healthcare materials. 2014 ; Vol. 3, No. 3. pp. 375-385.
Download
@article{c65059c39bb641cf9bb6c33de27ea859,
title = "Selectivity in Bone Targeting with Multivalent Dendritic Polyanion Dye Conjugates",
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.",
keywords = "Bisphosphonates, Bone targeting, Conjugates, Hydroxyapatite, Inflammation",
author = "Dominic Gr{\"o}ger and Michael Kerschnitzki and Marie Weinhart and Sabine Reimann and Tobias Schneider and Benjamin Kohl and Wolfgang Wagermaier and Gundula Schulze-Tanzil and Peter Fratzl and Rainer Haag",
year = "2014",
month = mar,
doi = "10.1002/adhm.201300205",
language = "English",
volume = "3",
pages = "375--385",
journal = "Advanced healthcare materials",
issn = "2192-2640",
publisher = "John Wiley and Sons Ltd",
number = "3",

}

Download

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 -

By the same author(s)