title: Stable Encapsulation of Air in Mesoporous Silica Nanoparticles: Fluorocarbon-Free Nanoscale Ultrasound Contrast Agents.
abstract: While gas-filled micrometer-sized ultrasound contrast agents vastly improve signal-to-noise ratios, microbubbles have short circulation lifetimes and poor extravasation from the blood. Previously reported fluorocarbon-based nanoscale contrast agents are more stable but their contrast is generally lower owing to their size and dispersity. The contrast agents reported here are composed of silica nanoparticles of ≈100 nm diameter that are filled with ≈3 nm columnar mesopores. Functionalization of the silica surface with octyl groups and resuspension with Pluronic F127 create particles with pores that remain filled with air but are stable in buffer and serum. Administration of high intensity focused ultrasound (HIFU) allows sensitive imaging of the silica nanoparticles down to 10(10) particles mL(-1) , with continuous imaging for at least 20 min. Control experiments with different silica particles supported the hypothesis that entrapped air could be pulled into bubble nuclei, which can then in turn act as acoustic scatterers. This process results in very little hemolysis in whole blood, indicating potential for nontoxic blood pool imaging. Finally, the particles are lyophilized and reconstituted or stored in PBS (phosphate-buffered saline, at least for four months) with no loss in contrast, indicating stability to storage and reformulation.
authors.affiliation: Department of Chemical and Biological Engineering, University of Colorado Boulder, Boulder, CO, 80303, USA.
authors.forename: Adem
authors.initials: A
authors.lastname: Yildirim
authors.affiliation: Department of Chemical and Biological Engineering, University of Colorado Boulder, Boulder, CO, 80303, USA.|Department of Mechanical Engineering, University of Colorado Boulder, Boulder, CO, 80309, USA.
authors.forename: Rajarshi
authors.initials: R
authors.lastname: Chattaraj
authors.affiliation: Department of Chemical and Biological Engineering, University of Colorado Boulder, Boulder, CO, 80303, USA.
authors.forename: Nicholas T
authors.initials: NT
authors.lastname: Blum
authors.affiliation: Department of Chemical and Biological Engineering, University of Colorado Boulder, Boulder, CO, 80303, USA.
authors.forename: Galen M
authors.initials: GM
authors.lastname: Goldscheitter
authors.affiliation: Department of Chemical and Biological Engineering, University of Colorado Boulder, Boulder, CO, 80303, USA.
authors.forename: Andrew P
authors.initials: AP
authors.lastname: Goodwin
mesh_terms: D000388:Air; D003287:Contrast Media / Q000737:chemistry*; D005466:Fluorocarbons / Q000737:chemistry*; D053758:Nanoparticles / Q000737:chemistry*; D010316:Particle Size; D020442:Poloxamer / Q000737:chemistry; D012822:Silicon Dioxide / Q000737:chemistry*; D014463:Ultrasonography / Q000379:methods
chemical_list: D003287:Contrast Media; D005466:Fluorocarbons; D020442:Poloxamer; D012822:Silicon Dioxide
keywords: aur encapsulation; biomedical applications; imaging; mesoporous silica; surface science; ultrasound contrast agents