Phosphorescent nanoparticles for quantitative measurements of oxygen profiles in vitro and in vivo.

Abstract

We present the development and characterization of nanoparticles loaded with a custom phosphor; we exploit these nanoparticles to perform quantitative measurements of the concentration of oxygen within three-dimensional (3-D) tissue cultures in vitro and blood vessels in vivo. We synthesized a customized ruthenium (Ru)-phosphor and incorporated it into polymeric nanoparticles via self-assembly. We demonstrate that the encapsulated phosphor is non-toxic with and without illumination. We evaluated two distinct modes of employing the phosphorescent nanoparticles for the measurement of concentrations of oxygen: 1) in vitro, in a 3-D microfluidic tumor model via ratiometric measurements of intensity with an oxygen-insensitive fluorophore as a reference, and 2) in vivo, in mouse vasculature using measurements of phosphorescence lifetime. With both methods, we demonstrated micrometer-scale resolution and absolute calibration to the dissolved oxygen concentration. Based on the ease and customizability of the synthesis of the nanoparticles and the flexibility of their application, these oxygen-sensing polymeric nanoparticles will find a natural home in a range of biological applications, benefiting studies of physiological as well as pathological processes in which oxygen availability and concentration play a critical role.

• Authors: Nak Won Choi, Scott S Verbridge, Rebecca M Williams, Jin Chen, Ju-Young Kim, Russel Schmehl, Cornelia E Farnum, Warren R Zipfel, Claudia Fischbach, Abraham D Stroock
• Journal: Biomaterials (Biomaterials) Vol. 33 Issue 9 Pg. 2710-22 (Mar 2012) ISSN: 1878-5905 [Electronic] Netherlands
• PMID: 22240511 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2011 Elsevier Ltd. All rights reserved.

Chemical References

• Biocompatible Materials
• Oxygen

Topics

• Animals
• Biocompatible Materials (pharmacology)
• Calibration
• Cell Death (drug effects)
• Cell Line, Tumor
• Female
• Humans
• Imaging, Three-Dimensional
• Light
• Luminescent Measurements (methods)
• Mice
• Microfluidics
• Models, Biological
• Nanoparticles (chemistry)
• Oxygen (metabolism)
• Particle Size
• Scattering, Radiation
• Spectrophotometry, Ultraviolet