title: 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.affiliation: School of Chemical and Biomolecular Engineering, Cornell University, Ithaca, NY 14853, USA. nakwon.choi@kist.re.kr
authors.forename: Nak Won
authors.initials: NW
authors.lastname: Choi
authors.forename: Scott S
authors.initials: SS
authors.lastname: Verbridge
authors.forename: Rebecca M
authors.initials: RM
authors.lastname: Williams
authors.forename: Jin
authors.initials: J
authors.lastname: Chen
authors.forename: Ju-Young
authors.initials: JY
authors.lastname: Kim
authors.forename: Russel
authors.initials: R
authors.lastname: Schmehl
authors.forename: Cornelia E
authors.initials: CE
authors.lastname: Farnum
authors.forename: Warren R
authors.initials: WR
authors.lastname: Zipfel
authors.forename: Claudia
authors.initials: C
authors.lastname: Fischbach
authors.forename: Abraham D
authors.initials: AD
authors.lastname: Stroock
mesh_terms: D000818:Animals; D001672:Biocompatible Materials / Q000494:pharmacology; D002138:Calibration; D016923:Cell Death / Q000187:drug effects; D045744:Cell Line, Tumor; D005260:Female; D006801:Humans; D021621:Imaging, Three-Dimensional; D008027:Light; D008163:Luminescent Measurements / Q000379:methods*; D051379:Mice; D044085:Microfluidics; D008954:Models, Biological; D053758:Nanoparticles / Q000737:chemistry*; D010100:Oxygen / Q000378:metabolism*; D010316:Particle Size; D012542:Scattering, Radiation; D013056:Spectrophotometry, Ultraviolet
chemical_list: D001672:Biocompatible Materials; D010100:Oxygen