Protease degradable tethers for controlled and cell-mediated release of nanoparticles in 2- and 3-dimensions.

Published

Journal Article

Strategies to control the release rate of bioactive signals from tissue engineering scaffolds are essential for tissue regeneration and tissue engineering applications. Here we report on a strategy to achieve temporal control over nanoparticle release from biomaterials using cell-secreted proteases. This cell-triggered release approach utilizes peptides that are degraded by matrix metalloproteinases (MMPs) at different rates to immobilize nanoparticles directly to the biomaterial surface. Thus, the peptide-immobilized nanoparticles are released with temporal control through the action of cell-released MMPs. We found that release rates of peptide-immobilized nanoparticles were a function of peptide sensitivity to proteases, the number of tethers between the nanoparticle and the surface and the concentration of proteases used to induce release. Cellular internalization of the peptide-immobilized nanoparticles was also a function of the peptide sensitivity to proteases, the number of tethers between the nanoparticle and the surface and MMP expression profile of the cells. Similar trends were observed for peptide-immobilized nanoparticles inside micro-porous hydrogels, indicating protease sensitive tethers are effective in controlling release rate and internalization of nanoparticles. Such a temporal delivery strategy of nanoparticles loaded with therapeutic payloads (e.g. protein, DNA, siRNA) can be an ideal means to guide tissue formation.

Full Text

Duke Authors

Cited Authors

  • Tokatlian, T; Shrum, CT; Kadoya, WM; Segura, T

Published Date

  • November 2010

Published In

Volume / Issue

  • 31 / 31

Start / End Page

  • 8072 - 8080

PubMed ID

  • 20688389

Pubmed Central ID

  • 20688389

Electronic International Standard Serial Number (EISSN)

  • 1878-5905

International Standard Serial Number (ISSN)

  • 0142-9612

Digital Object Identifier (DOI)

  • 10.1016/j.biomaterials.2010.07.030

Language

  • eng