title: Toward in vivo detection of hydrogen peroxide with ultrasound molecular imaging.
abstract: We present a new class of ultrasound molecular imaging agents that extend upon the design of micromotors that are designed to move through fluids by catalyzing hydrogen peroxide (H₂O₂) and propelling forward by escaping oxygen microbubbles. Micromotor converters require 62 mm of H₂O₂ to move - 1000-fold higher than is expected in vivo. Here, we aim to prove that ultrasound can detect the expelled microbubbles, to determine the minimum H₂O₂ concentration needed for microbubble detection, explore alternate designs to detect the H₂O₂ produced by activated neutrophils and perform preliminary in vivo testing. Oxygen microbubbles were detected by ultrasound at 2.5 mm H₂O₂. Best results were achieved with a 400-500 nm spherical design with alternating surface coatings of catalase and PSS over a silica core. The lowest detection limit of 10-100 μm was achieved when assays were done in plasma. Using this design, we detected the H₂O₂ produced by freshly isolated PMA-activated neutrophils allowing their distinction from naïve neutrophils. Finally, we were also able to show that direct injection of these nanospheres into an abscess in vivo enhanced ultrasound signal only when they contained catalase, and only when injected into an abscess, likely because of the elevated levels of H₂O₂ produced by inflammatory mediators.
authors: Department of Radiology, University of California, 410 Dickinson St., San Diego, CA 92103, United States.
authors: Emilia S
authors: ES
authors: Olson
authors: Jahir
authors: J
authors: Orozco
authors: Zhe
authors: Z
authors: Wu
authors: Christopher D
authors: CD
authors: Malone
authors: Boemha
authors: B
authors: Yi
authors: Wei
authors: W
authors: Gao
authors: Mohammad
authors: M
authors: Eghtedari
authors: Joseph
authors: J
authors: Wang
authors: Robert F
authors: RF
authors: Mattrey
mesh_terms: D000818:Animals; D002374:Catalase / Q000737:chemistry; D006861:Hydrogen Peroxide / Q000032:analysis*; D006863:Hydrogen-Ion Concentration; D045423:Microbubbles; D008855:Microscopy, Electron, Scanning; D057054:Molecular Imaging / Q000379:methods*; D054118:Nanospheres / Q000737:chemistry; D009504:Neutrophils / Q000737:chemistry / Q000166:cytology; D051381:Rats; D017207:Rats, Sprague-Dawley; D014465:Ultrasonics / Q000295:instrumentation* / Q000379:methods
chemical_list: D006861:Hydrogen Peroxide; D002374:Catalase
keywords: Abscess; Hydrogen peroxide; Molecular imaging; Nanotechnology; Ultrasound
references: J Acoust Soc Am. 2000 Apr;107(4):2272-80
references: 10790053
references: Nanoscale. 2012 Apr 7;4(7):2447-53
references: 22374514
references: J Am Chem Soc. 2011 Mar 23;133(11):3776-9
references: 21366297
references: Antioxid Redox Signal. 2006 Jul-Aug;8(7-8):1249-52
references: 16910772
references: Nat Mater. 2007 Oct;6(10):765-9
references: 17704780
references: Am J Cardiol. 1983 Sep 1;52(5):607-9
references: 6613886
references: Invest Radiol. 1984 Sep-Oct;19(5):438-46
references: 6511250
references: ACS Nano. 2009 Jan 27;3(1):4-9
references: 19206241
references: Cancer Res. 1991 Feb 1;51(3):794-8
references: 1846317
references: Int J Tissue React. 1987;9(1):39-43
references: 3596956
references: Invest Radiol. 1991 Sep;26(9):792-8
references: 1938289
references: J Biol Chem. 1984 Jan 10;259(1):399-405
references: 6323407
references: Trends Pharmacol Sci. 2003 Sep;24(9):471-8
references: 12967772
references: Ann Biomed Eng. 2012 Sep;40(9):2059-68
references: 22562306
references: J Immunol Methods. 1989 Jul 6;121(1):105-13
references: 2474025
references: Acad Radiol. 2002 Aug;9 Suppl 2:S279-81
references: 12188248
references: Arch Biochem Biophys. 2004 Feb 15;422(2):119-24
references: 14759598
references: Sci Am. 2009 May;300(5):72-7
references: 19438052
references: Adv Mater. 2012 Oct 2;24(38):5205-11
references: 22811026
references: J Am Chem Soc. 2011 Aug 10;133(31):11862-4
references: 21749138