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H2Sn imaging in NAFLD. (a) Confocal microscopy images of endogenous H2Sn in L02 cells with the nano-probe PPG-Np-RhPhCO (4.8 μM). The first column: incubation with the nano-probe for 2 h; the second column: incubation with 100 μM Na2S for 1 h before treatment with the nano-probe for 2 h; the third column: incubation with 0.5 mM FFA for 12 h before treatment with the nano-probe for 2 h; the fourth column: incubation with 0.5 mM FFA for 12 h, and then incubation with 100 μM Na2S for 1 h before treatment with the nano-probe for 2 h; the fifth to seventh columns: pretreatment with AOAA (300 μM), PPG (1 mM), or PDTC (200 μM) for 2 h, respectively, before treatment with 0.5 mM FFA for 12 h and then the nano-probe for 2 h. Green channel (425–475 nm), red channel (570–620 nm), pseudocolor ratio images (green channel/red channel). λex = 405 nm. Scale bar: 20 μm. (b) Average fluorescence intensity ratios (FGreen/FRed) of live L02 cells under the conditions in (a). Data represent mean standard error (n = 5 independent experiments; 60 cells). (c) Western blot analysis showing MPST expression in L02 cells upon treatment with FFA and PDTC, respectively. The MPST relative abundance was normalized with β-actin relative abundance. n = 3 independent experiments. Statistical significance was calculated with unpaired two-tailed Student's t-tests. *p < 0.05, **p < 0.01, ***p < 0.001. (d) Proposed schematic of H2Sn generation in the NAFLD model. Addition of Na2S can increase H2S, the precursor of H2Sn, thus promoting the further increase of H2Sn in the NAFLD model. Meanwhile, increased MPST expression stimulated by FFA can also promote the generation of H2Sn by producing more H2S or direct reaction with H2S. Black arrows denote the signal pathway in FFA treatment; blue arrows denote the H2S participational pathway; the red dashed arrow indicates possible ROS effects in the regulation of H2Sn. PDTC is the MPST inhibitor
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Hydrogen polysulfides (H2S
n
, n > 1) have continuously been proved to act as important signal mediators in many physiological processes. However, the physiological role of H2S
n
and their signaling pathways in complex diseases, such as the most common liver disease, nonalcoholic fatty liver disease (NAFLD), have not been elucidated due to lack o...
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Small molecule modified antitumor drug conjugate nanoparticles have the advantages of high drug loading, simple synthesis and preparation, and better biocompatibility. Due to the large demand for exogenous α-linolenic acid (ALA) by tumor cells, we synthesized α-linolenic acid-paclitaxel conjugate (ALA-PTX) and prepared α-linolenic acid-pacl...
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... Ratiometric molecular probes and ratiometric nanoprobes are collectively referred to as ratiometric probes. Molecular probes are systems that form strong and inherently irreversible bonds with their target analyte [40]; Nanoprobes are constructed primarily by functionalizing nanomaterials with specific molecular ligands [41,42]; Alternatively, some nanoprobes can be obtained by combining molecular probes with nanoparticles [43,44]. Therefore, in the following sections, the molecular probes and the nanoprobes are represented as probes. ...
Biosensing by optical probes is bringing about a revolution in our understanding of physiological and pathological states. Conventional optical probes for biosensing are prone to inaccurate detection results due to various analyte-independent factors that can lead to fluctuations in the absolute signal intensity. Ratiometric optical probes provide built-in self-calibration signal correction for more sensitive and reliable detection. Probes specifically developed for ratiometric optical detection have been shown to significantly improve the sensitivity and accuracy of biosensing. In this review, we focus on the advancements and sensing mechanism of ratiometric optical probes including photoacoustic (PA) probes, fluorescence (FL) probes, bioluminescence (BL) probes, chemiluminescence (CL) probes and afterglow probes. The versatile design strategies of these ratiometric optical probes are discussed along with a broad range of applications for biosensing such as sensing of pH, enzymes, reactive oxygen species (ROS), reactive nitrogen species (RNS), glutathione (GSH), metal ions, gas molecules and hypoxia factors, as well as the fluorescence resonance energy transfer (FRET)-based ratiometric probes for immunoassay biosensing. Finally, challenges and perspectives are discussed.
... CCB (E)-8-(diethylamino)-4-(4-(9-ethyl-9H-carbazol-3-yl)s tyryl)-2,2-difluoro-2H,5H-2l4,3l3-[1,3,2]dioxaborinin o [5,4-c]chromen-5-one [42] PX-P (Z)-3-(2-cyano-3-(5-(4-(diphenylamino)phenyl)furan -2-yl) crylamido)-SKL [43] RTFP 9-(2-carboxyphenyl)-11-(7-(diethylamino)-2-oxo-2Hchromen-yl)-2,3,6,7-tetrahydro-1H,5H-pyrano [2,3-f]pyrido [3,2,1-ij]uinolin-12-ium [44] Np-RhPhCO [45] N,N-diphenyl-4-(5-(pyridin-4-yl)thiophen-2-yl)aniline [38] Lip-YB ...
... hromen-2-one [41] CCB 03B 3-(4-(diphenylamino)phenyl)-N,N-diethyl-2,2-difluo ro-2H-2l4-benzo[e] [1,2] [5,4-c]chromen-5-one [42] PX-P (Z)-3-(2-cyano-3-(5-(4-(diphenylamino)phenyl)furan -2-yl) crylamido)-SKL [43] RTFP 9-(2-carboxyphenyl)-11-(7-(diethylamino)-2-oxo-2Hchromen-yl)-2,3,6,7-tetrahydro-1H,5H-pyrano [2,3-f]pyrido [3,2,1-ij]uinolin-12-ium [44] Np-RhPhCO [5,4-c]chromen-5-one [42] PX-P 03B 3-(4-(diphenylamino)phenyl)-N,N-diethyl-2,2-difluo ro-2H-2l4-benzo[e] [1,2] [5,4-c]chromen-5-one [42] PX-P (Z)-3-(2-cyano-3-(5-(4-(diphenylamino)phenyl)furan -2-yl) crylamido)-SKL [43] RTFP 9-(2-carboxyphenyl)-11-(7-(diethylamino)-2-oxo-2Hchromen-yl)-2,3,6,7-tetrahydro-1H,5H-pyrano [2,3-f]pyrido [3,2,1-ij]uinolin-12-ium [44] Np-RhPhCO [45] (Z)-3-(2-cyano-3-(5-(4-(diphenylamino)phenyl)furan-2-yl) crylamido)-SKL [43] RTFP 03B 3-(4-(diphenylamino)phenyl)-N,N-diethyl-2,2-difluo ro-2H-2l4-benzo[e] [1,2] [5,4-c]chromen-5-one [42] PX-P (Z)-3-(2-cyano-3-(5-(4-(diphenylamino)phenyl)furan -2-yl) crylamido)-SKL [43] RTFP 9-(2-carboxyphenyl)-11-(7-(diethylamino)-2-oxo-2Hchromen-yl)-2,3,6,7-tetrahydro-1H,5H-pyrano [2,3-f]pyrido [3,2,1-ij]uinolin-12-ium [44] Np-RhPhCO ...
... Zhang and coworkers designed and synthesized a fluorescent probe, Np-RhPhCO ( Figure 15), based on through-bond energy transfer (TBET) mechanism for fluorescence detection of intracellular hydrosulfide [45]. Np-RhPhCO consisted of a naphthalene donor and a rhodamine acceptor, where a recognition site with high response activity to hydropolysulfide was introduced onto the rhodamine acceptor by screening experiments. ...
Fatty liver diseases are a spectrum of liver disorders consisting of the benign fatty liver, which could eventually lead to cirrhosis or even hepatocellular cancer (HCC) without timely treatment. Therefore, early diagnosis is crucial for fatty liver diseases. Liver biopsy is regarded as the gold standard in the diagnosis of fatty liver diseases. However, it is not recommended for routine use due to its invasiveness and complicated operation. Thus, it is urgent to diagnose fatty liver diseases with non-invasive and precise methods. In this regard, fluorescence imaging technology has attracted intensive attention and become a robust non-invasive method for fatty liver visualization, and a series of fluorescent probes are being intensively designed to track the biomarkers in fatty liver. In this brief review, the small molecular fluorescent probes employed in fatty liver are summarized, mainly focusing on the last four years. Moreover, current opportunities and challenges in the development of fluorescent probes for fatty liver will be highlighted.
... With H 2 S, it demonstrated green fluorescence at 508 nm (excited at 386 nm) and only yielded a slight fluorescence at 576 nm when excited at 386 nm with H 2 S n . However, when excited at 511 nm, the probe yielded a strong orange fluorescence (at ~580 nm) with H 2 S n and only a weak fluorescence with thiols and H 2 S. Yuan et al. developed a ratiometric probe, Np-RhPhCO, for H 2 S n [50]. ...
Sulfane sulfur species such as hydropersulfides (RSSH), polysulfides (RSnR), and hydrogen polysulfides (H2Sn) are critically involved in sulfur-mediated redox signaling, but their detailed mechanisms of action need further clarification. Therefore, there is a need to develop selective and sensitive sulfane sulfur detection methods to gauge a better understanding of their functions. This review summarizes current detection methods that include cyanolysis, chemical derivatization and mass spectrometry, proteomic analysis, fluorescent probes, and resonance synchronous/Raman spectroscopic methods. The design principles, advantages, applications, and limitations of each method are discussed, along with suggested directions for future research on these methods. The development of robust detection methods for sulfane sulfur species will help to elucidate their mechanisms and functions in biological systems.
... Fluorescence imaging of the generation of H 2 S n in NAFLD cell; ROS/H 2 S/H 2 S n signaling pathway revealed in a drug induced-NAFLD cell model. [55] Np-RhPhCO with amphiphilic copolymer ...
... Furthermore, combined with the H 2 S probe and ONOO À fluorescent probes previously developed by our group, we revealed the ROS/H 2 S/H 2 S n crosstalk signaling pathways in the drug-treated NAFLD model, indicating the increased ROS would stimulate MPST and CSE to trigger the enhancement of H 2 S and H 2 S n ( Figure 12D). [55] ...
Nonalcoholic fatty liver disease (NAFLD), emerging as one of the most common chronic liver diseases including simple steatosis and non‐alcoholic steatohepatitis (NASH), is likely to progress to liver fibrosis and hepatic carcinoma if not treated in time. Therefore, early diagnosis and treatment of NAFLD are necessary. Currently, liver biopsy, as the gold standard for clinical diagnosis of NAFLD, is not widely accepted by patients due to its invasiveness. However, other non‐invasive methods that had been reported for NAFLD (such as magnetic resonance imaging, positron emission tomography, and ultrasound) still suffer from low resolution and sensitivity, which are available as a guide for liver biopsy sometimes. As a non‐invasive modality with high spatiotemporal resolution and superior sensitivity, optical imaging methods have been widely favored in recent years, mainly including fluorescence imaging, photoacoustic imaging, and bioluminescence imaging. With these optical imaging approaches, a series of optical probes based on optical and molecular‐specific design have been developed for the biomarker diagnosis and research of diseases. In this review, we summarize the existing non‐invasive optical imaging probes for the detection of biomarkers in NAFLD, including microenvironment (viscosity, polarity), ROS, RSS, ions, proteins, and nucleic acids. Design strategies for optical imaging probes and their applications in NAFLD bioimaging are discussed and focused on. We also highlight the potential challenges and prospects of designing new generations of optical imaging probes in NAFLD studies, which will further enhance the diversity, practicality, and clinical feasibility of NAFLD research.
... [38] An appealing strategy was reported for the design of an H 2 S nresponsive nanoprobe by Zhang et al, which composed of three steps: screening of the recognition moiety to response H 2 S n , combining two fluorophores with through-bond energy transfer effect to construct a ratiometric sensor, and the loading of the sensor in self-assembled amphiphilic copolymer to from the nanoprobe with advanced performances ( Figure 8A). [39] The nanoprobe PPGÀ Np-RhPhCO had been successfully applied to observe the production of endogenous and exogenous H 2 S n in cells, zebrafish and the liver tissues of NAFLD mice. Moreover, the probe helped to elucidate the relationship between ROS and H 2 S n , a stronger signal was exhibited in the mice stimulated by the co-treatment with FFA and APAP than individual treatment, suggesting the ROS can control the release of the antioxidant H 2 S n to maintain the redox balance. ...
... [45] The fluorescence signal of HeLa cells pre-incubated with probe 1 was distinctly attenuated after the incubation with a typical thiol-depleting agent N-methylmaleimide (NMM), [46] and recovered after the re-addition of thiols. Since GSH, Cys and Hcy share similar molecular structure and biological activities, the discriminative sensing of their co- [39] Copyright 2020, The Royal Society of Chemistry. (B) Schematic illustration for the synthesis steps of 1-PEI-DCNPs. ...
Liver injury‐related diseases have aroused widespread concern due to their extreme unpredictability, acute onset, and severe consequences. Nowadays, the clinical prediction and assessment of liver injury mainly focus on histopathological and serological approaches, which require a tedious process and sometimes invasive biopsy. Over the past decades, fluorescence imaging techniques have emerged for the diagnosis of diseases owing to their noninvasiveness, high fidelity and ease of operation. With regard to liver injury, fluorescent probes have been delicately designed to respond to a variety of endogenous biomolecules to precisely offer comprehensive information about the lesion site. Herein, we make a brief summary and discussion about the design strategies and applications of recently reported fluorescent biosensors responsive to a series of biomarkers involved in liver injury. The potential prospects and remaining challenges are also discussed to promote the progression in this field.
