Article abstract
Nature Materials 7, 248 - 254 (2008)
Published online: 3 February 2008 | doi:10.1038/nmat2116
Subject Categories: Polymers | Biomedical materials
Biofunctional polymer nanoparticles for intra-articular targeting and retention in cartilage
Dominique A. Rothenfluh1, Harry Bermudez1,2, Conlin P. O'Neil1 & Jeffrey A. Hubbell1
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 
1. 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.
- Institute of Bioengineering and Institute of Chemical Sciences and Engineering, Ecole Polytechnique Fédérale de Lausanne, CH-1015 Lausanne, Switzerland
- Department of Polymer Science and Engineering, University of Massachusetts, Amherst, Massachusetts 01003, USA
Correspondence to: Jeffrey A. Hubbell1 e-mail: jeffrey.hubbell@epfl.ch
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