Biofunctional polymer nanoparticles for intra-articular targeting and retention in cartilage

Dominique A. Rothenfluh, Harry Bermudez, Conlin P. O'Neil, Jeffrey A. Hubbell

Research output: Contribution to journalArticle

182 Scopus citations

Abstract

The extracellular matrix of dense, avascular tissues presents a barrier to entry for polymer-based therapeutics, such as drugs encapsulated within polymeric particles. Here, we present an approach by which polymer nanoparticles, sufficiently small to enter the matrix of the targeted tissue, here articular cartilage, are further modified with a biomolecular ligand for matrix binding. This combination of ultrasmall size and biomolecular binding converts the matrix from a barrier into a reservoir, resisting rapid release of the nanoparticles and clearance from the tissue site. Phage display of a peptide library was used to discover appropriate targeting ligands by biopanning on denuded cartilage. The ligand WYRGRL was selected in 94 of 96 clones sequenced after five rounds of biopanning and was demonstrated to bind to collagen II α1. Peptide-functionalized nanoparticles targeted articular cartilage up to 72-fold more than nanoparticles displaying a scrambled peptide sequence following intra-articular injection in the mouse.

Original languageEnglish (US)
Pages (from-to)248-254
Number of pages7
JournalNature Materials
Volume7
Issue number3
DOIs
StatePublished - Mar 2008

ASJC Scopus subject areas

  • Chemistry(all)
  • Materials Science(all)
  • Condensed Matter Physics
  • Mechanics of Materials
  • Mechanical Engineering

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