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

174 Citations (Scopus)

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
Pages (from-to)248-254
Number of pages7
JournalNature Materials
Volume7
Issue number3
DOIs
StatePublished - Mar 1 2008
Externally publishedYes

Fingerprint

cartilage
Cartilage
Polymers
Peptides
Nanoparticles
peptides
nanoparticles
Ligands
polymers
Tissue
matrices
ligands
Peptide Library
Bacteriophages
clearances
collagens
Collagen
entry
mice
drugs

ASJC Scopus subject areas

  • Engineering(all)

Cite this

Biofunctional polymer nanoparticles for intra-articular targeting and retention in cartilage. / Rothenfluh, Dominique A.; Bermudez, Harry; O'Neil, Conlin P.; Hubbell, Jeffrey A.

In: Nature Materials, Vol. 7, No. 3, 01.03.2008, p. 248-254.

Research output: Contribution to journalArticle

Rothenfluh, DA, Bermudez, H, O'Neil, CP & Hubbell, JA 2008, 'Biofunctional polymer nanoparticles for intra-articular targeting and retention in cartilage', Nature Materials, vol. 7, no. 3, pp. 248-254. https://doi.org/10.1038/nmat2116
Rothenfluh, Dominique A. ; Bermudez, Harry ; O'Neil, Conlin P. ; Hubbell, Jeffrey A. / Biofunctional polymer nanoparticles for intra-articular targeting and retention in cartilage. In: Nature Materials. 2008 ; Vol. 7, No. 3. pp. 248-254.
@article{d0864f43589b4053a374c2a9a6b5a6a8,
title = "Biofunctional polymer nanoparticles for intra-articular targeting and retention in cartilage",
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.",
author = "Rothenfluh, {Dominique A.} and Harry Bermudez and O'Neil, {Conlin P.} and Hubbell, {Jeffrey A.}",
year = "2008",
month = "3",
day = "1",
doi = "10.1038/nmat2116",
language = "English",
volume = "7",
pages = "248--254",
journal = "Nature Materials",
issn = "1476-1122",
publisher = "Nature Publishing Group",
number = "3",

}

TY - JOUR

T1 - Biofunctional polymer nanoparticles for intra-articular targeting and retention in cartilage

AU - Rothenfluh, Dominique A.

AU - Bermudez, Harry

AU - O'Neil, Conlin P.

AU - Hubbell, Jeffrey A.

PY - 2008/3/1

Y1 - 2008/3/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=39749198122&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=39749198122&partnerID=8YFLogxK

U2 - 10.1038/nmat2116

DO - 10.1038/nmat2116

M3 - Article

C2 - 18246072

AN - SCOPUS:39749198122

VL - 7

SP - 248

EP - 254

JO - Nature Materials

JF - Nature Materials

SN - 1476-1122

IS - 3

ER -