Biofunctional polymer nanoparticles for intra-articular targeting and retention in cartilage
- 3 February 2008
- journal article
- Published by Springer Science and Business Media LLC in Nature Materials
- Vol. 7 (3), 248-254
- https://doi.org/10.1038/nmat2116
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 alpha1. 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.Keywords
This publication has 36 references indexed in Scilit:
- Fetuin mediates hepatic uptake of negatively charged nanoparticles via scavenger receptorInternational Journal of Pharmaceutics, 2007
- Synchronous selection of homing peptides for multiple tissues byin vivophage displayThe FASEB Journal, 2006
- Tumor Vascular Permeability, Accumulation, and Penetration of Macromolecular Drug CarriersJNCI Journal of the National Cancer Institute, 2006
- Discovery of 3-OH-3-methylpipecolic hydroxamates: Potent orally active inhibitors of aggrecanase and MMP-13Bioorganic & Medicinal Chemistry Letters, 2005
- Osteoarthritis — an untreatable disease?Nature Reviews Drug Discovery, 2005
- Synthesis and Physicochemical Characterization of End-Linked Poly(ethylene glycol)-co-peptide Hydrogels Formed by Michael-Type AdditionBiomacromolecules, 2003
- Screening Phage-Displayed Combinatorial Peptide LibrariesMethods, 2001
- Phage DisplayChemical Reviews, 1997
- Organ targeting In vivo using phage display peptide librariesNature, 1996
- Liposome-incorporated corticosteroids. II. Therapeutic activity in experimental arthritis.Annals Of The Rheumatic Diseases, 1979