title: Measurement of plasma volume using fluorescent silica-based nanoparticles.
abstract: Plasma volume (PV) is an important determinant of cardiovascular function and organ perfusion, and it is the target of infusion and diuretic therapies in daily clinical practice. Despite its fundamental importance PV is not commonly measured because available methods of tracer dilution are reliant on dye substances that suffer from numerous drawbacks including binding plasma proteins, spectral changes, and clearance kinetics that complicate analysis and interpretation. To address these issues, we have tested the utility of fluorescent nanoparticles comprised of a dye-rich silica core and polyethylene glycol-coated shell. Photophysical and visual analysis showed discrete size-gradated nanoparticle populations could be synthesized within a distribution tolerance of ±4 nm, which were optically unaffected in the presence of plasma/albumin. In normal mice, the cutoff for renal filtration of nanoparticles from blood into urine was ≤11 nm. A linear relationship between body weight and PV was readily determined in mice administered far red fluorescent nanoparticles sized either 20 or 30 nm. PV measurements using nanoparticles were correlated to values obtained with Evans blue dye. Induced expansion or contraction of PV was demonstrated with albumin or furosemide administration, respectively, in mice. Longitudinal experiments >30 min required matched untreated control mice to correct for nanoparticle loss (≈30%) putatively to the reticuloendothelial/phagocyte system. Collectively, the findings support a nanotechnology-based solution to methodological problems in measure of PV, notably in clinical settings where information on hemodynamic changes may improve treatment of injury and disease.
authors.affiliation: National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Christoph
authors.initials: C
authors.lastname: Eisner
authors.forename: Hooisweng
authors.initials: H
authors.lastname: Ow
authors.forename: Tianxin
authors.initials: T
authors.lastname: Yang
authors.forename: Zhanjun
authors.initials: Z
authors.lastname: Jia
authors.forename: Emilios
authors.initials: E
authors.lastname: Dimitriadis
authors.forename: Lingli
authors.initials: L
authors.lastname: Li
authors.forename: Kenneth
authors.initials: K
authors.lastname: Wang
authors.forename: Josephine
authors.initials: J
authors.lastname: Briggs
authors.forename: Mark
authors.initials: M
authors.lastname: Levine
authors.forename: Jurgen
authors.initials: J
authors.lastname: Schnermann
authors.forename: Michael Graham
authors.initials: MG
authors.lastname: Espey
mesh_terms: D000818:Animals; D001798:Blood Proteins / Q000737:chemistry; D005456:Fluorescent Dyes; D007668:Kidney / Q000502:physiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018625:Microscopy, Atomic Force; D053758:Nanoparticles; D010953:Plasma Volume; D011092:Polyethylene Glycols; D012822:Silicon Dioxide; D013050:Spectrometry, Fluorescence
chemical_list: D001798:Blood Proteins; D005456:Fluorescent Dyes; D011092:Polyethylene Glycols; D012822:Silicon Dioxide