DOTAM Derivatives as Active Cartilage-Targeting Drug Carriers for the Treatment of Osteoarthritis

Hai Yu Hu, Ngee Han Lim, Danping Ding-Pfennigdorff, Joachim Saas, K. Ulrich Wendt, Olaf Ritzeler, Hideaki Nagase, Oliver Plettenburg, Carsten Schultz, Marc Nazare

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

(Graph Presented). Targeted drug-delivery methods are crucial for effective treatment of degenerative joint diseases such as osteoarthritis (OA). Toward this goal, we developed a small multivalent structure as a model drug for the attenuation of cartilage degradation. The DOTAM (1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid amide)-based model structure is equipped with the cathepsin D protease inhibitor pepstatin A, a fluorophore, and peptide moieties targeting collagen II. In vivo injection of these soluble probes into the knee joints of mice resulted in 7-day-long local retention, while the drug carrier equipped with a scrambled peptide sequence was washed away within 6-8 h. The model drug conjugate successfully reduced the cathepsin D protease activity as measured by release of GAG peptide. Therefore, these conjugates represent a promising first drug conjugate for the targeted treatment of degenerative joint diseases.

Original languageEnglish (US)
Pages (from-to)383-388
Number of pages6
JournalBioconjugate Chemistry
Volume26
Issue number3
DOIs
StatePublished - Mar 18 2015
Externally publishedYes

Fingerprint

Drug Carriers
Cartilage
Osteoarthritis
Peptides
Cathepsin D
Derivatives
Pharmaceutical Preparations
Fluorophores
Model structures
Protease Inhibitors
Amides
Collagen
Peptide Hydrolases
Therapeutics
Knee Joint
Degradation
Acids
Injections
Drug Delivery Systems
Cathepsins

ASJC Scopus subject areas

  • Biotechnology
  • Bioengineering
  • Biomedical Engineering
  • Pharmacology
  • Pharmaceutical Science
  • Organic Chemistry

Cite this

Hu, H. Y., Lim, N. H., Ding-Pfennigdorff, D., Saas, J., Wendt, K. U., Ritzeler, O., ... Nazare, M. (2015). DOTAM Derivatives as Active Cartilage-Targeting Drug Carriers for the Treatment of Osteoarthritis. Bioconjugate Chemistry, 26(3), 383-388. https://doi.org/10.1021/bc500557s

DOTAM Derivatives as Active Cartilage-Targeting Drug Carriers for the Treatment of Osteoarthritis. / Hu, Hai Yu; Lim, Ngee Han; Ding-Pfennigdorff, Danping; Saas, Joachim; Wendt, K. Ulrich; Ritzeler, Olaf; Nagase, Hideaki; Plettenburg, Oliver; Schultz, Carsten; Nazare, Marc.

In: Bioconjugate Chemistry, Vol. 26, No. 3, 18.03.2015, p. 383-388.

Research output: Contribution to journalArticle

Hu, HY, Lim, NH, Ding-Pfennigdorff, D, Saas, J, Wendt, KU, Ritzeler, O, Nagase, H, Plettenburg, O, Schultz, C & Nazare, M 2015, 'DOTAM Derivatives as Active Cartilage-Targeting Drug Carriers for the Treatment of Osteoarthritis', Bioconjugate Chemistry, vol. 26, no. 3, pp. 383-388. https://doi.org/10.1021/bc500557s
Hu HY, Lim NH, Ding-Pfennigdorff D, Saas J, Wendt KU, Ritzeler O et al. DOTAM Derivatives as Active Cartilage-Targeting Drug Carriers for the Treatment of Osteoarthritis. Bioconjugate Chemistry. 2015 Mar 18;26(3):383-388. https://doi.org/10.1021/bc500557s
Hu, Hai Yu ; Lim, Ngee Han ; Ding-Pfennigdorff, Danping ; Saas, Joachim ; Wendt, K. Ulrich ; Ritzeler, Olaf ; Nagase, Hideaki ; Plettenburg, Oliver ; Schultz, Carsten ; Nazare, Marc. / DOTAM Derivatives as Active Cartilage-Targeting Drug Carriers for the Treatment of Osteoarthritis. In: Bioconjugate Chemistry. 2015 ; Vol. 26, No. 3. pp. 383-388.
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