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 journalArticlepeer-review

41 Scopus citations


(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
Issue number3
StatePublished - Mar 18 2015
Externally publishedYes

ASJC Scopus subject areas

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


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