ABSTRACT
Drug-induced liver injury (DILI) poses a significant risk to human health. Increasing evidence indicates that the superoxide anion (O2â¢-), as the precursor of the other reactive oxygen species, is key in the pathological processes associated with DILI. Nonetheless, understanding of the mechanisms of DILI is difficult due to the lack of an imaging tool for monitoring the fluctuation of O2â¢- levels during the progression of DILI. Herein, we developed an upconversion nanoprobe (Rbh-UCNs) for in vivo ratiometric tracking of endogenous O2â¢- in DILI. In this design, the addition of O2â¢- triggers the luminescent resonance energy transfer between Rbh and UCNs, which significantly enhances absorption centered at 534 nm and translates into a distinct decrease of the UCL emission at 543 nm, while the UCL emission peak at 654 nm and 800 nm are not significantly affected, offering a ratiometric UCL signal for the quantitative detection of O2â¢-. In addition, Rbh-UCNs could effectively visualize endogenous O2â¢- in living cells, zebrafish, and liver tissues upon stimulation with PMA or cisplatin. More importantly, tissue imaging of the liver region of mice revealed that the fluctuation of O2â¢- levels is associated with DILI and the protective effect of L-carnitine against DILI. Altogether, this study provides an available method for a deeper comprehension of the mechanisms underlying DILI and accelerating the development process of hepatoprotective medicines.
ABSTRACT
ß-galactosidase (ß-gal) is a diagnostic biomarker of primary ovarian cancers. The development of effective fluorescent probes for investigating the activity of ß-gal will be beneficial to cancer diagnosis. Herein, a near-infrared (NIR) excited ratiometric nanoprobe (DCM-ß-gal-UCNPs) by assembling pyranonitrile dye (DCM-ß-gal) on the surface of upconversion nanophosphors (UCNPs) was designed for the evaluation of ß-gal activity in vivo. Upon the interaction with ß-gal, a marked decrease of upconversion luminescence (UCL) signal in the green channel was observed owing to the luminescence resonance energy transfer from the UCNPs to pyranonitrile chromophore, whereas the NIR UCL emission at 800 nm was almost no influence. Thus, the ß-gal activity could be quantitatively detected by the UCL intensity ratio of UCL543 nm/UCL800 nm with the limit of detection of 3.1 × 10-4 U/mL. Moreover, DCM-ß-gal-UCNPs was effectively applied for monitoring ß-gal fluctuation in living cells and zebrafish by a ratiometric UCL signal excited by 980 nm laser. We envision that nanoprobe DCM-ß-gal-UCNPs might be used as a potential bioimaging tool to disclose more biological information of ß-gal in ß-gal-associated diseases in the future.
Subject(s)
Nanoparticles , Animals , Zebrafish , Light , Spectroscopy, Near-Infrared/methods , beta-GalactosidaseABSTRACT
Exploring a chemical imaging tool for visualizing the endogenous CO biosignaling molecule is of great importance in understanding the pathophysiological functions of CO in complex biological systems. Most of the existing CO fluorescent probes show excitation and emission in the region of ultraviolet and visible light, which are not suitable for application in in vivo deep-depth imaging of CO. Herein, a new near-infrared (NIR) to NIR upconversion luminescence (UCL) nanosystem for in vivo visualization of CO was developed, which possesses the merits of high selectivity and sensitivity, a deep tissue penetration depth, and a high signal-to-noise ratio. In this design, upon interaction with CO, the maxima absorption peak of the nanosystem showed a significant blue shift from 795 nm to 621 nm and triggered a remarkable turn-on NIR UCL signal due to the luminescence resonance energy transfer process. Leveraging this nanosystem, we achieved an NIR UCL visualization of the generation of CO biosignals caused by hypoxic, acute inflammation, or ischemic injury in living cells, zebrafish, and mice. Moreover, the protective effect of CO in zebrafish models of oxygen and glucose deprivation/reperfusion (OGD/R) and mice models of lipopolysaccharide-induced oxidative stress (LOS) and hepatic ischemia/reperfusion (HI/R) was also further verified. Therefore, this work discloses that the nanosystem not only serves as a promising nanoplatform to study biological signaling pathways of CO in pathophysiological events, but may also provide a powerful tool for HI/R injury diagnosis.
Subject(s)
Nanoparticles , Reperfusion Injury , Mice , Animals , Luminescence , Carbon Monoxide , Zebrafish , Reperfusion Injury/diagnostic imaging , Spectroscopy, Near-Infrared/methods , Nanoparticles/chemistryABSTRACT
Carbon monoxide (CO) is considered as the second gasotransmitter involved in a series of physiological and pathological processes. Although a number of organic fluorescent probes have been developed for imaging CO, these probes display excitation within the ultraviolet or visible range, which restrict their applications in the complex biosystems. In the present work, a strategy is developed to construct an upconversion nanoparticles-based nanosystem for upconversion luminescent (UCL) sensing CO. This nanosystem exhibits a fast response to CO with high sensitivity and selectivity in aqueous solution by a near-infrared-excited ratiometric UCL detection method. Meanwhile, laser scanning upconversion luminescence microscope experiments demonstrate that this nanosystem can visualize the endogenous CO bio-signaling in living cells, deep tissues, zebrafish, and living mice by ratiometric UCL imaging. In particular, this nanosystem has been successfully employed in visualization of the endogenous CO bio-signaling through up-regulation of heme oxygenase-1 (HO-1) in the progression of hypoxia, acute inflammation, or ischemic injury. This work demonstrates that the outstanding performance of the nanosystem not only can provide an effective tool for further understanding the role of CO in the physiological and pathological environment, but also may have great potential ability for tracking the expression of HO-1 in living systems.
Subject(s)
Carbon Monoxide , Nanoparticles , Animals , Carbocyanines , Luminescence , Mice , ZebrafishABSTRACT
Although being as an important chemical material in industry, hydrazine (N2H4) is highly toxic to the humans and animals. The development of sensitive methods for the detection of hydrazine is meaningful. Herein, we develop a new organic-inorganic hybrid nanoprobe for the detection of N2H4 based on luminescent resonance energy transfer (LRET) process. The nanoprobe contains N2H4-responsive NIR cyanine dye (CQM1) and α-cyclodextrin (CD) anchored on the surface of lanthanide-doped upconversion nanophosphors (UCNPs). In the presence of hydrazine, the hybrid materials (CQM1-UCNPs) showed the a large ratiometric luminescent signal change with high sensitivity and selectivity. More importantly, by taking advantage of ratiometric Upconversion luminescent (UCL) signal and the features of NIR emission/excitation, the nanoprobe was successfully applied for visualization of hydrazine in living cells for the first time.
Subject(s)
Coloring Agents , Fluorescence Resonance Energy Transfer , Animals , HeLa Cells , Humans , LuminescenceABSTRACT
The development of an inorganic-organic hybrid probe to more accurately detect ions in living systems is very challenging but highly desirable. Here we combined upconversion nanoparticles with the electrically active ferrocene group to detect Cu2+ in living cells. The as-prepared probe displays three different signal changes in absorption, emission, and electrochemical behavior, respectively, during Cu2+ ion detection. Moreover, this new probe has been demonstrated to show high stability and adaptability. In addition, bioimaging testing reveals that this probe is suitable for detecting and visualizing Cu2+ in A549 cells with low cytotoxicity.