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A Ratiometric Two-photon Fluorescent Probe for in vivo Hydrogen Polysulfides Detection and Imaging During Lipopolysaccharide-Induced Acute Organs Injury Jing Zhang, Xiaoyan Zhu, Xiaoxiao Hu, Hongwen Liu, Jin Li, Lili Feng, Xia Yin, Xiao-Bing Zhang, and Weihong Tan Anal. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.analchem.6b03702 • Publication Date (Web): 09 Nov 2016 Downloaded from http://pubs.acs.org on November 10, 2016
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Analytical Chemistry
A Ratiometric Two-photon Fluorescent Probe for in vivo Hydrogen Polysulfides Detection and Imaging During Lipopolysaccharide-Induced Acute Organs Injury
Jing Zhang, Xiao-Yan Zhu, Xiao-Xiao Hu, Hong-Wen Liu, Jin Li, Li-Li Feng, Xia Yin*, Xiao-Bing Zhang*, and Weihong Tan Molecular Science and Biomedicine Laboratory, State Key Laboratory of Chemo/Biosensing and Chemometrics, College of Chemistry and Chemical Engineering, Collaborative Innovation Center for Chemistry and Molecular Medicine, Hunan University, Changsha 410082.
* To whom correspondence should be addressed. E-mail:
[email protected],
[email protected] ACS Paragon Plus Environment
Analytical Chemistry
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Abstract Acute organ injury observed during sepsis, caused by an uncontrolled release of inflammatory mediators, such as lipopolysaccharide (LPS), is quite fatal. The development of efficient methods for early diagnosis of sepsis and LPS-induced acute organ injury in living systems is of great biomedical importance. In living systems, cystathionine γ-lyase (CSE) can be overexpressed due to LPS, and H2Sn can be formed by CSE-mediated cysteine metabolism. Thus, acute organ injury during sepsis may be correlated with H2Sn levels, making accurate detection of H2Sn in living systems of great physiological and pathological significance. In this work, our previously reported fluorescent platform was employed to design and synthesize a FRET-based ratiometric two-photon (TP) fluorescent probe TPR-S, producing a large emission shift in the presence of H2Sn. In this work, a naphthalene derivative two-photon fluorophore was chosen as the energy donor; a rhodol derivative fluorophore served as the acceptor. The 2-fluoro-5-nitrobenzoate group of probe TPR-S reacted with H2Sn and was selectively removed to release the fluorophore, resulting in a fluorescent signal decrease at 448 nm and enhancement at 541 nm. The ratio value of fluorescence intensity between 541 nm and 448 nm (I541 nm/I448 nm) varied from 0.13 to 8.12 (~62 fold) with the H2Sn concentration changing from 0 to 1 mM. The detection limit of the probe was 0.7 µM. Moreover, the probe was applied for imaging H2Sn in living cells, tissues, and organs of LPS-induced acute organ injury, which demonstrated its practical application in complex biosystems as a potential method to achieve early diagnosis of LPS-induced acute organ injury.
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Analytical Chemistry
Introduction Sepsis, a kind of systemic inflammatory response syndrome, often occurs during infection.1,2 When the disease evolves, inflammatory mediators, such as lipopolysaccharide (LPS), can spread throughout the body, leading to acute kidney injury,2-4 acute hepatic/liver injury,5-7 and acute lung injury,8-14. Almost half of patients with sepsis develop acute organ injury, and 70% of these patients with concomitant sepsis and acute organ injury will die.15,16 2,17 Therefore, the development of efficient methods for early diagnosis of LPS-induced acute organ injury are urgently needed. It is reported that H2Sn could be formed from cystathionine γ-lyase (CSE)-mediated cysteine metabolism,18-21 and CSE is over-expressed when induced by inflammatory mediators, such as LPS.21 So, the level of H2Sn is directly related to CSE, and mediated by LPS. Therefore, monitoring the level of H2Sn may be a potential strategy for early diagnosis of LPS-induced acute organ injury. However, research on the biological role of H2Sn is still in its infancy. A number of traditional methods, such as UV spectroscopy22 and mass spectrometry (MS),23 have been applied to investigate H2Sn. However, these methods are limited due to their poor sensitivity and low operability in organisms. Fluorescence assays may be the most feasible technique for detection of H2Sn in living systems, due to their numerous advantages, including real-time spatial imaging, high sensitivity, and minimal harm to biological samples.24,25 Based on the reaction of H2Sn-mediated aziridines ring-opening and benzodithiolone formation, several fluorescent probes for H2Sn have been reported.26-35 However, most of these fluorescent probes are excited by single-photons at short wavelengths (usually
