TY - JOUR
T1 - A Ratiometric Acoustogenic Probe for in Vivo Imaging of Endogenous Nitric Oxide
AU - Reinhardt, Christopher J.
AU - Zhou, Effie Y.
AU - Jorgensen, Michael D.
AU - Partipilo, Gina
AU - Chan, Jefferson
N1 - Funding Information:
This work was supported by the Chemistry-Biology Interface Training Grant (T32 GM070421 to C.J.R. and E.Y.Z.), the National Science Foundation Graduate Research Fellowship Program (NGE-1144245 to E.Y.Z.), the Springborn Fellowship (to E.Y.Z.), the Alfred P. Sloan fellowship (FG-2017-8964 to J.C.), and the Neurotechnology for Memory and Cognition Award (to M.D.J.). Major funding for the 500 MHz Bruker CryoProbe was provided by the Roy J. Carver Charitable Trust (Muscatine, Iowa; Grant No. 15-4521) to the School of Chemical Sciences NMR Lab. The Q-Tof Ultima mass spectrometer was purchased in part with a grant from the National Science Foundation, Division of Biological Infrastructure (DBI-0100085). We acknowledge Professor Elvira de Mejia (Food Science and Human Nutrition, UIUC) for providing RAW 264.7 macrophage cells. We also acknowledge the Core Facilities at the Carl R. Woese Institute for Genomic Biology for access to the Zeiss LSM 700 Confocal Microscope and corresponding software.
Publisher Copyright:
© 2018 American Chemical Society.
PY - 2018/1/24
Y1 - 2018/1/24
N2 - Photoacoustic (PA) imaging is an emerging imaging modality that utilizes optical excitation and acoustic detection to enable high resolution at centimeter depths. The development of activatable PA probes can expand the utility of this technology to allow for detection of specific stimuli within live-animal models. Herein, we report the design, development, and evaluation of a series of Acoustogenic Probe(s) for Nitric Oxide (APNO) for the ratiometric, analyte-specific detection of nitric oxide (NO) in vivo. The best probe in the series, APNO-5, rapidly responds to NO to form an N-nitroso product with a concomitant 91 nm hypsochromic shift. This property enables ratiometric PA imaging upon selective irradiation of APNO-5 and the corresponding product, tAPNO-5. Moreover, APNO-5 displays the requisite photophysical characteristics for in vivo PA imaging (e.g., high absorptivity, low quantum yield) as well as high biocompatibility, stability, and selectivity for NO over a variety of biologically relevant analytes. APNO-5 was successfully applied to the detection of endogenous NO in a murine lipopolysaccharide-induced inflammation model. Our studies show a 1.9-fold increase in PA signal at 680 nm and a 1.3-fold ratiometric turn-on relative to a saline control.
AB - Photoacoustic (PA) imaging is an emerging imaging modality that utilizes optical excitation and acoustic detection to enable high resolution at centimeter depths. The development of activatable PA probes can expand the utility of this technology to allow for detection of specific stimuli within live-animal models. Herein, we report the design, development, and evaluation of a series of Acoustogenic Probe(s) for Nitric Oxide (APNO) for the ratiometric, analyte-specific detection of nitric oxide (NO) in vivo. The best probe in the series, APNO-5, rapidly responds to NO to form an N-nitroso product with a concomitant 91 nm hypsochromic shift. This property enables ratiometric PA imaging upon selective irradiation of APNO-5 and the corresponding product, tAPNO-5. Moreover, APNO-5 displays the requisite photophysical characteristics for in vivo PA imaging (e.g., high absorptivity, low quantum yield) as well as high biocompatibility, stability, and selectivity for NO over a variety of biologically relevant analytes. APNO-5 was successfully applied to the detection of endogenous NO in a murine lipopolysaccharide-induced inflammation model. Our studies show a 1.9-fold increase in PA signal at 680 nm and a 1.3-fold ratiometric turn-on relative to a saline control.
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U2 - 10.1021/jacs.7b10783
DO - 10.1021/jacs.7b10783
M3 - Article
C2 - 29313677
AN - SCOPUS:85041126234
SN - 0002-7863
VL - 140
SP - 1011
EP - 1018
JO - Journal of the American Chemical Society
JF - Journal of the American Chemical Society
IS - 3
ER -