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Toward in vivo detection of hydrogen peroxide with ultrasound molecular imaging

Olson, Emilia S. and Orozco, Jahir and Wu, Zhe and Malone, Christopher D. and Yi, Boemha and Gao, Wei and Eghtedari, Mohammad and Wang, Joseph and Mattrey, Robert F. (2013) Toward in vivo detection of hydrogen peroxide with ultrasound molecular imaging. Biomaterials, 34 (35). pp. 8918-8924. ISSN 0142-9612 . PMCID PMC3794895. http://resolver.caltech.edu/CaltechAUTHORS:20180123-113900256

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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 (H_2O_2) and propelling forward by escaping oxygen microbubbles. Micromotor converters require 62 mm of H_2O_2 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 H_2O_2 concentration needed for microbubble detection, explore alternate designs to detect the H_2O_2 produced by activated neutrophils and perform preliminary in vivo testing. Oxygen microbubbles were detected by ultrasound at 2.5 mm H_2O_2. 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 H_2O_2 produced by inflammatory mediators.


Item Type:Article
Related URLs:
URLURL TypeDescription
https://doi.org/10.1016/j.biomaterials.2013.06.055DOIArticle
https://www.sciencedirect.com/science/article/pii/S0142961213007709#PublisherArticle
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3794895PubMed CentralArticle
Additional Information:© 2013 Elsevier Ltd. Received 7 May 2013, Accepted 26 June 2013, Available online 16 August 2013. T32-EB005970 provided salary support for EO; Beatriu de Pinoìs Fellowship from the Government of Catalonia provided support for J.O; W.G. is a HHMI International Student Research fellow; Study was supported by ICMIC P50 CA128346 and NSF CBET 0853375. We wish to thank Siemens Medical Solutions for providing the Sequoia 512 scanner as an equipment loan. We would also like to thank Allan Cortes, Ashley Pourazary, Christopher Barback and Jacqueline Corbeil for providing technical assistance and for helpful discussion.
Funders:
Funding AgencyGrant Number
Beatriu de Pinoìs (Catalonia)UNSPECIFIED
Howard Hughes Medical Institute (HHMI)UNSPECIFIED
NIHP50 CA128346
NSFCBET-0853375
Subject Keywords:UltrasoundNanotechnologyHydrogen peroxideMolecular imagingAbscess
PubMed Central ID:PMC3794895
Record Number:CaltechAUTHORS:20180123-113900256
Persistent URL:http://resolver.caltech.edu/CaltechAUTHORS:20180123-113900256
Official Citation:Emilia S. Olson, Jahir Orozco, Zhe Wu, Christopher D. Malone, Boemha Yi, Wei Gao, Mohammad Eghtedari, Joseph Wang, Robert F. Mattrey, Toward in vivo detection of hydrogen peroxide with ultrasound molecular imaging, Biomaterials, Volume 34, Issue 35, November 2013, Pages 8918-8924, ISSN 0142-9612, https://doi.org/10.1016/j.biomaterials.2013.06.055. (https://www.sciencedirect.com/science/article/pii/S0142961213007709)
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:84477
Collection:CaltechAUTHORS
Deposited By: Ruth Sustaita
Deposited On:31 Jan 2018 23:10
Last Modified:01 Feb 2018 00:36

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