Near-infrared fluorescent probe for the imaging of viscosity in fatty liver mice and valuation of drug efficacy.

Fatty liver disease affects at least 25 percent of the population worldwide and is a severe metabolic syndrome. Viscosity is closely related to fatty liver disease, so it is urgent to develop an effective tool for monitoring viscosity. Herein, a NIR fluorescent probe called MBC-V is developed for imaging viscosity, consisting of dimethylaniline and malonitrile-benzopyran. MBC-V is non-fluorescent in low viscosity solutions due to intramolecular rotation. In high viscosity solution, the intramolecular rotation of MBC-V is suppressed and the fluorescence is triggered. MBC-V has long emission wavelength at 720 nm and large Stokes shift about 160 nm. Moreover, MBC-V can detect changes in cell viscosity in fatty liver cells, and can image the therapeutic effects of drug in fatty liver cells. By taking advantage of NIR emission, MBC-V can be used as an imaging tool for fatty liver disease and a way to evaluate the therapeutic effect of drug for fatty liver disease.

Elongin B promotes breast cancer progression by ubiquitinating tumor suppressor p14/ARF.

Elongin B (ELOB), a pivotal element in the ELOB/c-Cullin2/5-SOCS-box E3 ubiquitin-protein ligase complex, plays a significant role in catalyzing the ubiquitination and subsequent degradation of a broad spectrum of target proteins. Notably, it is documented to facilitate these processes. However, the regulatory role of ELOB in breast cancer remains ambiguous. In this study, through bio-informatic analysis of The Cancer Genome Atlas and Fudan University Shanghai Cancer Center database, we demonstrated that ELOB was over-expressed in breast cancer tissues and was related to unfavorable prognosis. Additionally, pathway enrichment analysis illustrated that high expression of ELOB was associated with multiple cancer promoting pathways, like cell cycle, DNA replication, proteasome and PI3K - Akt signaling pathway, indicating ELOB as a potential anticancer target. Then, we confirmed that both in vivo and in vitro, the proliferation of breast cancer cells could be significantly suppressed by the down-regulation of ELOB. Mechanically, immunoprecipitation and in vivo ubiquitination assays prompted that, as the core element of Cullin2-RBX1-ELOB E3 ligase (CRL2) complex, ELOB regulated the ubiquitination and the subsequent degradation of oncoprotein p14/ARF. Moreover, the anticancer efficacy of erasing ELOB could be rescued by simultaneous knockdown of p14/ARF. Finally, through analyzing breast cancer tissue microarrays and western blot of patient samples, we demonstrated that the expression of ELOB in tumor tissues was elevated in compared to adjacent normal tissues. In conclusion, ELOB is identified to be a promising innovative target for the drug development of breast cancer by promoting the ubiquitination and degradation of oncoprotein p14/ARF.

Effect of hydrothermal pH values on the morphology of special microspheres of lignin-based porous carbon and the mechanism of carbon dioxide adsorption.

The study reports the economic and sustainable syntheses of a lignin-based porous carbon (LPC) for CO2 capture application. The pH values of hydrothermal solution affected the polymerization and aromatization of spheroidization, with morphological changes from blocky to microsphere. In addition, the reliable mechanisms of CO2 adsorption were proposed by combining experiments with Gaussian16 simulations based on DFT. The electrostatic attraction of oxygen-containing functional groups and the diffusivity resistance of CO2 in the pores are the key factors for the CO2 adsorption. ​The carboxyl groups have the strongest electrostatic attraction to CO2. LPC-pH 1 has the highest carboxyl group content, possessing a CO2 adsorption capacity of up to 5.10 mmol/g at 0℃, 1 bar. Furthermore, CO2 diffusion resistance became a main factor as the adsorption temperature increases. The innovative combination of quantum chemical calculations and microscopic properties provides a viable pathway for an insight into the future control of lignin-based carbon formation.

A near-infrared fluorescent probe for viscosity: Differentiating cancer cells from normal cells and dual-modal imaging in tumor mice.

As a basic parameter of the intracellular microenvironment, viscosity is closely related to the development of cancer. Thus, it is necessary to utilize a sensitive tool to visualize the viscosity in tumor cells and mice, which is helpful for the diagnosis of cancer. Herein, a novel dual-modal probe (IX-V) that has a near-infrared fluorescence (NIRF) and photoacoustic (PA) response to viscosity is synthesized. In low viscosity media, the probe has no fluorescence. With the increase of viscosity, the fluorescence is produced in the near-infrared region due to the inhibition of the TICT process. At the same time, the probe shows different photoacoustic (PA) signals in different viscosity media. Most notably, the viscosity in tumor cells has been imaged successfully by the application of IX-V, and the probe can effectively distinguish cancer cells from normal cells co-cultured in one dish by the difference of fluorescence intensity. In addition, the probe has been used for dual-modal imaging (NIRF and PA) of viscosity in tumor mice, which provides a tool for exploring the relationship between viscosity and diseases. That is to say, IX-V can achieve complementary imaging effects and has great application prospects in the tumor diagnosis.

Biomass-based controllable morphology of carbon microspheres with multi-layer hollow structure for superior performance in supercapacitors.

The electrochemical properties of corn starch (CS)-based hydrothermal carbon microsphere (CMS) electrode materials for supercapacitor are closely related to their structures. Herein, cetyltrimethyl ammonium bromide (CTAB) was used as a soft template to form the corn starch (CS)-based carbon microspheres with radial hollow structure in the inner and middle layers by hydrothermal and sol-gel method. Due to the introduction of multi-layer hollow structure of carbon microsphere, more micropores were produced during CO2 activation, which increased the specific surface area and improved the capacitance performance. Compared to commercial activated carbon, the four different morphologies of corn starch CMS had better electrochemical performances. Consequently, the proposed CO2-(CTAB)-CS-CS exhibits a high discharge specific capacitance of 242.5F/g at 1 A/g in three-electrode system with 6 M KOH electrolyte, better than commercial activated carbon with 208.5F/g. Moreover, excellent stability is achieved for CO2-(CTAB)-CS-CS with approximately 97.14 % retention of the initial specific capacitance value after 10,000 cycles at a current density of 2 A/g, while the commercial activated carbon has 86.96 % retention. This implies that the corn starch-based multilayer hollow CMS could be a promising electrode material for high-performance supercapacitors.

Long-Term Imaging of Cys in Cells and Tumor Mice by a Solid-State Fluorescence Probe.

Cysteine is an important biological thiol and is closely related to cancer. It remains a challenge to develop a probe that can provide long-term fluorescence detection and imaging of Cys in cells as well as in living organisms. Here, a solid-state fluorophore HTPQ is combined with an acrylate group to construct a solid-state fluorescent probe HTPQC for Cys recognition. The fluorescence of the probe is quenched when the photoinduced electron transfer (PET) process is turned on and the excited-state intramolecular proton transfer (ESIPT) process is turned off. In the presence of Cys, an obvious solid-state fluorescence signal can be observed. The double quenching mechanism makes the probe HTPQC have the advantages of high sensitivity, good selectivity, and high contrast of biological imaging. Due to low cytotoxicity, the probe HTPQC can be used to detect exogenous and endogenous Cys in living cells and is capable of imaging over long periods of time. By making full use of long wavelengths, the probe can be applied for the detection of Cys levels in tumor mice and equipped with the ability to conduct long-term imaging in vivo.

A near-infrared fluorescent probe for detecting hydrogen sulfide with high selectivity in cells and ulcerative colitis in mice.

Although hydrogen sulfide (H2S) is a well-known toxic gas, its vital role as a gas transmitter in various physiological and pathological processes of living systems cannot be ignored. Relevant investigations indicate that endogenous H2S is involved in the development of ulcerative colitis pathology and is overexpressed in ulcerative colitis, and hence can be considered as an ulcerative colitis biomarker. Herein, an isophorone-xanthene-based NIR fluorescent probe (IX-H2S) was constructed to image H2S. Owing to its large conjugated structure, the probe exhibits a near-infrared emission wavelength of 770 nm with a large Stokes shift (186 nm). Moreover, IX-H2S has excellent selectivity for the detection of H2S without interference from other analytes including thiols. In addition, the probe has been successfully applied not only in fluorescence imaging of endogenous and exogenous H2S in living cells, but also in imaging of H2S in normal and ulcerative colitis mice. Encouraged by the eminent performance, IX-H2S is expected to be a potent "assistant" for the diagnosis of ulcerative colitis.

Dual Key-Activated Nir-I/II Fluorescence Probe for Monitoring Photodynamic and Photothermal Synergistic Therapy Efficacy.

As cancer markers, hydrogen peroxide (H2 O2 ) and viscosity play an essential role in the development of tumors. Meanwhile, based on the performance of near-infrared (NIR) fluorescence imaging and the high efficiency of photodynamic therapy (PDT) and photothermal therapy (PTT) synergistic therapy, it is urgent to develop a dual-key (H2 O2 and viscosity) activated fluorescence probe for cancer phototherapy. Herein, a NIR-I/II fluorescence probe named BX-B is reported. In the presence of both H2 O2 and viscosity, the fluorescence signal of NIR-I (810 nm) and NIR-II (945 nm) can be released. In the presence of H2 O2 , the PDT and PTT effects are observed. BX-B is used to monitor its therapeutic effects in cancer cells and tumor-bearing mice due to the increased viscosity caused by PDT and PTT. In addition, the tumors of mice treated with BX-B are almost completely ablated after the laser irradiation based on its PDT and PTT synergistic therapy. This work provides a reliable platform for effective cancer treatment and immediate evaluation of therapeutic effects.

A dual-channel fluorescent nanoprobe for accurate cancer diagnosis by sequential detection of adenosine triphosphate and sulfur dioxide.

Cancer is one of the major diseases that seriously endanger the health of all mankind. Accurate diagnosis of early cancer is the most promising way to reduce cancer harm and improve patient survival. However, many developed fluorescent probes for cancer imaging only have the function of identifying one marker, which cannot meet the needs of accurate diagnosis. Here, a fluorescent nanoprobe (CPH@ZIF-90) utilizing ZIF-90 to encapsulate SO2-sensitive dye (CPH) is synthesized for the sequential detection of ATP and SO2. The nanoprobe first interacts with ATP to release CPH, thus increasing the fluorescence at 685 nm and realizing the near-infrared (NIR) fluorescence detection of ATP. Then, SO2 acts on the released CPH through nucleophilic addition, affecting the π-conjugated structure of CPH and resulting in enhanced fluorescence at 580 nm. CPH@ZIF-90 exhibits satisfactory sensitivity and selectivity for sequential detection of ATP and SO2. Excitedly, CPH@ZIF-90 can sequentially image the endogenous ATP and SO2 in cells, showing sensitive fluorescence changes in dual channels (red and green). Due to the NIR emission properties of CPH@ZIF-90 and its ability to enrich in tumor, it is applied to monitor ATP and SO2 in mice and distinguish normal mice from tumor mice. The ability of CPH@ZIF-90 to sequentially detect two cancer-related biomarkers makes it provide meaningful assistance in accurate early diagnosis of cancer.

A near-infrared fluorescent probe for monitoring abnormal mitochondrial viscosity in cancer and fatty-liver mice model.

Viscosity is an important component of cell microenvironment, and abnormal mitochondrial viscosity is associated with many diseases such as tumor and fatty liver. Herein, a near-infrared fluorescence probe (QX-V) based on quinoline-xanthene dye for detecting viscosity is constructed. In high viscosity medium, the free rotation of single bond is inhibited and the fluorescence is released. The probe shows high sensitivity together with good selectivity. Notably, QX-V has a long excitation wavelength (710 nm) and emission wavelength (786 nm). At the same time, the probe is a positively charged molecule that can target mitochondria. QX-V can not only distinguish cancer cells from normal cells, but also make a distinction between normal cells and fatty hepatocytes. In addition, QX-V is used to image viscosity abnormality in tumor-bearing mice. The probe also has a good ability to image viscosity abnormality caused by liver injury in fatty-liver mice.

Near-Infrared Fluorescent Nanoprobes for Adenosine Triphosphate-Guided Imaging in Cancer and Fatty Liver Mice.

Adenosine triphosphate (ATP), as an indispensable biomolecule, is the main energy source of cells and is used as a marker for diseases such as cancer and fatty liver. It is of great significance to design a near-infrared fluorescent nanoprobe with excellent performance and apply it to various disease models. Here, a near-infrared fluorescent nanoprobe (ZIF-90@SiR) based on a zeolitic imidazole framework is proposed. The fluorescent nanoprobes are synthesized by encapsulating the dye (SiR) into the framework of ZIF-90. Upon the addition of ATP, the structure of the ZIF-90@SiR nanoprobe is disrupted and SiR is released to generate near-infrared fluorescence at 670 nm. In the process of ATP detection, ZIF-90@SiR shows high sensitivity and good selectivity. Moreover, the ZIF-90@SiR nanoprobe has good biocompatibility due to its low toxicity to cells. It is used for fluorescence imaging of ATP in living cells and thus distinguishing normal cells and cancer cells, as well as distinguishing fatty liver cells. Due to excellent near-infrared fluorescence properties, the ZIF-90@SiR nanoprobe can not only distinguish normal mice and tumor mice but also differentiate normal mice and fatty liver mice for the first time.

A Dual-Channel Fluorescent Nanoprobe for Sequential Detection of ATP and Peroxynitrite to Accurately Distinguish between Normal Cells and Cancer Cells.

Cancer is one of the biggest public enemies of global health with its high morbidity and mortality. Achieving early diagnosis is the most effective means of reducing cancer harm, which requires the use of powerful tools to accurately identify biomarkers. However, most of the reported fluorescent probes for cancer diagnosis can only detect one substance, which makes it difficult to meet the requirements of high accuracy. Here, a fluorescent nanoprobe (CPQ@ZIF-90) for sequential detection of ATP and ONOO- is constructed by encapsulating the ONOO- sensitive unit CPQ within ZIF-90. CPQ@ZIF-90 first reacts with ATP to release CPQ, which greatly enhances the fluorescence at 740 nm. Then, the released CPQ continues to react with ONOO- and is oxidatively cleaved by ONOO- to form a coumarin product with a small π-conjugated structure, which significantly enhances the fluorescence at 510 nm. CPQ@ZIF-90 shows high sensitivity and selectivity for the detection of ATP and then ONOO-. Moreover, CPQ@ZIF-90 has good biocompatibility and successfully realizes the sequential detection of a dual-channel fluorescence change of ATP and ONOO- in living cells and zebrafish and accurately distinguishes normal cells from cancer cells. CPQ@ZIF-90 is expected to be a potential tool for accurate cancer diagnosis through sequential detection of two cancer markers.

A HPQ-based far-red fluorescent probe for monitoring viscosity in mice model of acute inflammation.

Viscosity is an essential microenvironmental parameter, which is related to various diseases such as acute inflammation. So it is necessary to develop a probe to monitor viscosity changes during the inflammatory progression in vivo. Herein, a HPQ (2-(2'-hydroxyphenyl)-4(3H)-quinazolinone)-based fluorescent probe named HPQ-BI-V is prepared for detecting viscosity in biological systems. The introduction of benzindole groups extends the π conjugation of HPQ, resulting in far-red emission wavelength at 610 nm. When the viscosity raises from 3.11 cP to 567.1 cP, the fluorescence signal increases 711 times, indicating the high sensitivity of the probe. Furthermore, this probe displays excellent selectivity for viscosity in comparison with other interfering analytes. Furthermore, the probe has excellent photostability and outstanding response capability in the physiological pH range. Given these advantages, HPQ-BI-V can be applied for detecting viscosity changes in HepG2 cells and zebrafish. In particular, the probe can successfully visualize viscosity changes in acute inflammatory mice induced by LPS and the assessment of anti-inflammatory drug.

A nitrobenzoxadiazole-based near-infrared fluorescent probe for the specific imaging of H2S in inflammatory and tumor mice.

As a common gaseous signaling molecule, hydrogen sulfide (H2S) plays a vital role in physiology and pathology. The development of fluorescent probes for detecting H2S has attracted widespread attention. However, most of the reported fluorescent probes with nitrobenzoxadiazole (NBD) as the recognition group have been widely used to simultaneously detect biothiols and H2S, instead of specifically detecting H2S. Herein, a novel NBD-based near-infrared (NIR) fluorescent probe named CX-N for the detection of H2S is synthesized. The selectivity of CX-N for H2S is significantly higher than that for biothiols and other potential interferences. After reacting with H2S, CX-N shows a significant increase in NIR fluorescence (75-fold), large Stokes shift (155 nm) and fast response (4 min). And the possible response mechanism of CX-N to H2S is given and confirmed by HPLC and HRMS. Based on the low cytotoxicity of CX-N, it has been used for H2S imaging in live cells and zebrafish. More importantly, CX-N has also been successfully applied for the real-time imaging of H2S in inflammatory and tumor mice based on its NIR emission, which provides a reliable platform for the specific recognition of H2S in complex biological systems.

A dual-response fluorescent probe for simultaneously monitoring polarity and ATP during autophagy.

Autophagy plays a vital role in maintaining intracellular homeostasis through a lysosome-dependent intracellular degradation pathway, which is closely related to the polarity and ATP. Herein, the first example of the dual-response fluorescent probe Lyso-NRB was reported for visualizing the fluctuation of polarity and ATP in lysosomes during autophagy. Probe Lyso-NRB is non-fluorescent. After the decrease of polarity, Lyso-NRB exhibits significant green emission due to the unique intramolecular charge transfer (ICT) effect. Upon the addition of ATP, the probe can react with ATP to rapidly open the spirocycle of rhodamine and a strong red emission can be observed. Moreover, Lyso-NRB exhibits a high sensitivity and selectivity toward polarity and ATP. Most importantly, the probe possesses a good lysosome-targeting ability and is used for the real-time monitoring of lysosome polarity and ATP fluctuations during H2O2 or starvation induced autophagy in living cells. Interestingly, it is found that that ATP deficiency can induce autophagy to increase lysosome polarity. Furthermore, the probe is applied for imaging the change of polarity and ATP under oxidative stress induced autophagy in zebrafish. Therefore, this work holds great potential for tracking the autophagy procedure by detecting the changes of lysosome polarity and ATP, which makes it a potentially powerful tool for understanding the roles of autophagy in diverse biological processes.

[Analysis of Coexisting Gene with NRAS in Acute Myeloid Leukemia].

OBJECTIVE: To investigate the coexisting mutations and clinical significance of Homo sapiens neuroblastoma RAS viral oncogene homolog (NRAS) gene in acute myeloid leukemia (AML) patients. METHODS: High-throughput DNA sequencing and Sanger sequencing were used to detect 51 gene mutations. The occurrence, clinical characteristics and treatment efficacy of coexisting genes with NRAS were investigated. RESULTS: A total of 57 NRAS mutations (17.5%) were detected in 326 patients with AML. Compared with the patients in NRAS non-mutation group, patients in the mutant group were younger (P=0.018) and showed lower platelet count (P=0.033), but there was no significant difference in peripheral leukocyte count, hemoglobin, and sex. For FAB classification, NRAS mutation and M2 subtype showed mutually exclusive (P=0.038). Among 57 patients carried with NRAS mutation, 51 (89.5%) patients carried with other gene mutations, 25 (43.9%) carried with double gene mutations, 10 (17.5%) carried with 3 gene mutations, and 16 (28.1%) corried with ≥ 4 gene mutations. The most common coexisting gene mutation was KRAS (24.6%, 14/57), followed by FLT3-ITD (14.0%, 8/57), RUNX1 (12.3%, 7/57), NPM1 (10.5%, 6/57), PTPN11 (10.5%, 6/57), DNMT3A (10.5%, 6/57) and so on. The age (P=0.013, P=0.005) and peripheral platelet count (P=0.007, P=0.021) of patients with NPM1 or DNMT3A mutations were higher than those of the patients with wild type, but there was no significant difference in peripheral leukocyte count and hemoglobin. Also, there was no significant difference in age, peripheral leukocyte count, hemoglobin, and peripheral platelet count between the patients in KRAS, FLT3-ITD, RUNX1 or PTPN11 mutant group and the wild group. Patients with FLT3-ITD mutations showed a lower complete remission (CR) rate (P=0.044). However, there was no significant difference in CR rate between the patients with KRAS, NPM1, RUNX1, PTPN11 or DNMT3A mutations and the wild group. The CR rate of the patents with single gene mutation, double gene mutations, 3 gene mutations, and≥ 4 gene mutations were decreased gradually, and there was no significant difference in CR rate between pairwise comparisons. CONCLUSION: The mutation rate of NRAS mutation is 17.5%, 89.5% of AML patients with NRAS mutation coexist with additional gene mutations. The type of coexisting mutations has a certain impact on clinical characteristics and CR rate of patients with AML.

A tumor-targeting near-infrared fluorescent probe for real-time imaging ATP in cancer cells and mice.

Adenosine triphosphate (ATP) is an important biomolecule, which is the primary source of cellular energy. In particular, an abnormal metabolism of ATP level has been took part in many diseases, such as cancer. Thus, developing an effective fluorescent probe for tumor-targeting imaging of ATP is great importance for in-depth understanding the functions of ATP in tumor invasion and matastasis. In this work, we present the design and synthesis of a tumor-targeting near-infrared (NIR) fluorescent probe named Bio-SiR. Bio-SiR is mainly composed of three parts: si-rhodamine-based fluorophore, diethylenetriamine-based recognition group and biotin-based tumor-targetable group. When Bio-SiR reacts with ATP, a turn-on fluorescence at 675 nm (NIR region) is observed clearly, which is suitable for its application in mice. In addition, due to a concurrent effect from dual recognition sites, the probe Bio-SiR displays excellent selectivity for ATP over other potential biological analytes. Under the guidance of biotin group, Bio-SiR can be successfully used for imaging ATP in cancer cells. Furthermore, live-cell imaging allows us to directly real-time monitor the dynamic change of ATP in cancer cells. In particular, this is the first tumor-targeting NIR small-molecule fluorescent probe for endogenous ATP imaging in tumor-bearing mice. These features demonstrate that this probe is a useful imaging tool for expounding the function of ATP in cancer.

Angiography-derived radial wall strain predicts coronary lesion progression in non-culprit intermediate stenosis.

BACKGROUND: Intermediate coronary lesions (ICLs) are highly prevalent but ported mixed prognosis. Radial strain has been associated with plaque vulnerability, yet its role in predicting lesion progression is largely unknown. The purpose of this study was to determine the predictive value of angiography-derived radial wall strain (RWS) for progression of untreated non-culprit ICLs. METHODS: Post-hoc analysis was conducted in a study cohort including 603 consecutive patients with 808 ICLs identified at index procedure with angiographic follow-up of up to two years. RWS analysis was performed on selected angiographic frames with minimal foreshortening and vessel overlap. Lesion progression was defined as ≥ 20% increase in percent diameter stenosis. RESULTS: Lesion progression occurred in 49 ICLs (6.1%) with a median follow-up period of 16.8 months. Maximal RWS (RWSmax), frequently located at the proximal and throat plaque regions, distinguished progressive ICLs from silent ones. The largest area under the curve value of 0.75 (95% CI: 0.67-0.82, P < 0.001) was reached at the optimal RWSmax cutoff value of > 12.6%. According to this threshold, 178 ICLs were classified as having a high strain pattern. Exposure to a high strain amplitude with RWSmax > 12.6% was independently associated with an increased risk of lesion progression (adjusted HR = 6.82, 95% CI: 3.67-12.66, P < 0.001). CONCLUSIONS: Assessment of RWS from coronary angiography is feasible and provides independent prognostic value in patients with untreated ICLs.

Accurate Fluorescence Diagnosis of Cancer Based on Sequential Detection of Hydrogen Sulfide and pH.

Cancer ranks as a leading cause of death in every country of the world. However, if they are discovered early, a lot of cancers can be prevented or cured. Discovering and monitoring cancer markers are the main methods for early diagnosis of cancer. To date, many fluorescent probes designed and used for early cancer diagnosis can only react with a single marker, which always causes insufficient accuracy in complex systems. Herein, a novel near-infrared (NIR) fluorescent probe (CyO-DNP) for the sequential detection of H2S and H+ is synthesized. In this probe, a heptamethine dye is selected as the fluorophore and a 2,4-dinitrophenyl (DNP) ether is chosen as recognition group. In the presence of H2S, CyO-DNP is transformed into CyO, which exhibits an intense fluorescence at 663 nm. Then, H+ induces the protonation of CyO to obtain CyOH, and the final fluorescence emission at 793 nm significantly enhances. Owing to the low cytotoxicity and the NIR fluorescence emission, CyO-DNP can sequentially monitor endogenous H2S and H+ in cancer cells and image exogenous and endogenous H2S and H+ in mice. It is worth mentioning that CyO-DNP can effectively avoid the false positive signal caused by the liver and kidney and discriminate normal mice and tumor mice accurately. For all we know, CyO-DNP is the first fluorescent probe for early accurate diagnosis of cancer by sequentially detecting H2S and H+.

A near-infrared fluorescent probe with large Stokes shift for imaging Cys in tumor mice.

Cysteine (Cys), a kind of small molecule biological thiol, not only involves in the regulation of physiological processes, but also is considered a marker of tumor. However, it is challenging to develop suitable probe for detecting Cys in tumors. In this paper, a near-infrared (NIR) fluorescent probe named IX for Cys has been designed and synthesized. The probe shows a NIR emission peak at 770 nm with large Stokes shift (180 nm) upon adding Cys. It displays high sensitivity to Cys with 6-fold increase of fluorescence intensity. Meanwhile, IX has the high selectivity to Cys over other potential interference such as Hcy and GSH, which have similar structure with Cys. In addition, a possible mechanism of fluorescence enhancement is the reaction of IX with Cys to release IX-OH, which is verified by fluorescence spectra, MS and HPLC. Next, IX can selectively image Cys in HCT-116 cells thanks to the low cytotoxicity. Most important of all, the fluorescent probe IX has visualized Cys in HCT116-xenograft tumor mice due to the near-infrared properties with large Stokes shift.