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Quantitation of nanoparticle accumulation in flow using optimized microfluidic chambers.

J Kusunose1, M K J Gagnon, J W Seo

  • 1Department of Biomedical Engineering, University of California , Davis, CA , USA.

Journal of Drug Targeting
|October 2, 2013
PubMed
Summary

Researchers developed VCAM-1-targeted nanoparticles, including dendrimers and liposomes, for atherosclerosis. These nanocarriers showed specific binding to endothelial cells in microfluidic chambers under flow conditions.

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Area of Science:

  • Biomedical Engineering
  • Nanotechnology
  • Cardiovascular Research

Background:

  • Vascular cell adhesion molecule-1 (VCAM-1) targeting peptide VHPKQHR shows promise for atherosclerosis.
  • Nanoparticles like dendrimers and liposomes can be functionalized with targeting moieties.

Purpose of the Study:

  • Develop VCAM-1-targeted nanoparticles for enhanced endothelial accumulation under shear stress.
  • Create robust microfluidic chambers for flow cytometric analysis of cell-nanoparticle interactions.

Main Methods:

  • Synthesized VHP-peptide, VHP-dendrimers (bisbidentate/radial, with/without N-terminal acetylation), and VHP-peptide liposomes.
  • Assessed nanoparticle binding to human umbilical vein endothelial cells under varying shear conditions (0 or 2.9 dyne/cm²).
  • Fabricated and characterized polydimethylsiloxane microfluidic chambers for cell-based assays.

Main Results:

  • Liposomes exhibited the highest accumulation efficiency; dendrimers also showed specific binding.
  • N-terminal acetylation decreased dendrimer binding; bisbidentate dendrimers outperformed radial ones.
  • Liposome binding increased 300% under shear, while dendrimer binding decreased 65%.

Conclusions:

  • Optimized dendrimers and liposomal nanocarriers demonstrate specific accumulation on endothelial cells.
  • Microfluidic chambers were successfully engineered to support cell-based nanoparticle studies under flow.