Tumor Microenvironment Activatable Nanoprodrug System for In Situ Fluorescence Imaging and Therapy of Liver Cancer.

The development of new imaging and treatment nanoprodrug systems is highly demanded for diagnosis and therapy of liver cancer, a severe disease characterized by a high recurrence rate. Currently, available small molecule drugs are not possible for cancer diagnosis because of the fast diffusion of imaging agents and low efficacy in treatment due to poor water solubility and significant toxic side effects. In this study, we report the development of a tumor microenvironment activatable nanoprodrug system for the diagnosis and treatment of liver cancer. This nanoprodrug system can accumulate in the tumor site and be selectively activated by an excess of hydrogen peroxide (H2O2) in the tumor microenvironment, releasing near-infrared solid-state organic fluorescent probe (HPQCY-1) and phenylboronic acid-modified camptothecin (CPT) prodrug. Both HPQCY-1 and CPT prodrugs can be further activated in tumor sites for achieving more precise in situ near-infrared (NIR) fluorescence imaging and treatment while reducing the toxic effects of drugs on normal tissues. Additionally, the incorporation of hydrophilic multivalent chitosan as a carrier effectively improved the water solubility of the system. This research thus provides a practical new approach for the diagnosis and treatment of liver cancer.

High-fidelity fluorescent probes for visualizing the inhibitory behavior of selenium on cadmium uptake in rice.

Cadmium (Cd), a widespread and highly toxic environmental contaminant, has seriously impacted the growth of rice and the quality of its products. Hence, it is crucial to monitor and employ robust means to reduce Cd levels in rice, and selenium (Se) has been proven to chelate cadmium ion (Cd2+) in rice with rational use. Herein, for the first time, the reported selenocysteine (Sec) probe NN-Sec and the newly designed Cd2+ probe SCP were chosen as visualization tools to monitor Sec-inhibited Cd2+ uptake in rice. Specifically, reduced fluorescence of rice precultured with Cd2+ was observed by SCP after Se application, while similarly decreased fluorescence of rice pretreated with Se was observed by NN-Sec after Cd2+ addition. The diminished fluorescence indicated the formation of Cd-Se complexes reduced the Cd2+ content in rice. Additionally, it was Cd2+ and Se that entered the rice causing the fluorescence generation, as demonstrated by inductively coupled plasma mass spectrometry (ICP-MS). To conclude, the two probes successfully visualized Se inhibited Cd2+ uptake in rice, which could provide a robust tool for supporting the development of novel organic fertilizers and reagents to reduce Cd2+ content in rice and the environment.

Rationally Constructed De Novo Fluorescent Nanosensor for Nitric Oxide Detection and Imaging in Living Cells and Inflammatory Mice Models.

For the early diagnosis and effective evaluation of treatment effects of inflammation, a de novo bioanalytical method is urgently needed to monitor the metabolite nitric oxide (NO) associated with inflammatory diseases. However, developing a reliable detection method with excellent water solubility, biocompatibility, long retention time, and blood circulation is still challenging. In this work, we reported for the first time a de novo host-guest self-assembled nanosensor CTA for the quantitative detection and visualization of NO levels in inflammatory models. CTA mainly consists of two parts: (i) an adamantyl-labeled guest small-molecule RN-adH containing a classical response moiety o-phenylenediamine for a chemical-specific response toward NO and fluorophore rhodamine B with excellent optical properties as an internal reference for self-calibration and (ii) a remarkable water-soluble and biocompatible supramolecular ß-cyclodextrin polymer (Poly-ß-CD) host. In the presence of NO, the o-phenylenediamine unit was reacted with NO at a low pH value of ∼7.0, accompanied by changes in the intensity of the two emission peaks corrected for each other and the change in fluorescence color of the CTA solution from fuchsia to pink. Furthermore, CTA was an effective tool for NO detection with a fast response time (∼60 s), high selectivity, and sensitivity (LOD: 22.3 nM). Impressively, the CTA nanosensor has successfully achieved the targeted imaging of NO in living inflammatory RAW 264.7 cells and mice models with satisfactory results, which can provide a powerful molecular tool for the visualization and assessment of the occurrence and development of NO-related inflammatory diseases in complex biosystems.

Rational construction of a robust nanoprobe for highly selective and sensitive nitrite and formaldehyde detection and imaging in real foods.

Nitrite (NO2-) and formaldehyde (FA) are practice common food hazards, seriously threatening human health. Herein, for the first time a de novo nanoprobe, named MTB, with a single response group exhibiting different optical signals for NO2-/FA was reported, which had the following characteristics: i) An adamantane-labeled small molecule NI-adH grafted with polycyclodextrin (Poly-ß-CD) to form MTB with excellent water-solubility and biocompatibility. ii) O-phenylenediamine (OPD) with photoinduced electron transfer (PET) played both a fluorescence quencher and as NO2-/FA trappers. Interestingly, fixed on pH6.0, OPD rapidly reacted with NO2- forming triazoles, inhibiting the PET effect and releasing bright fluorescence at 530 nm. While adding FA, OPD ultrafast formed Schiff-base, and MTB absorption red-shifted from 452 nm to 545 nm. Moreover, MTB exhibited excellent selectivity, high sensitivity (21.8 nM/17.1 nM), and rapid response towards (60 s/65 s) NO2-/FA. Impressively, MTB has been successfully adopted to detect NO2-/FA in real foods with satisfactory results.

A Review for In Vitro and In Vivo Detection and Imaging of Gaseous Signal Molecule Carbon Monoxide by Fluorescent Probes.

Carbon monoxide (CO) is a vital endogenous gaseous transmitter molecule involved in the regulation of various physiological and pathological processes in living biosystems. In order to investigate the biological function of CO, many technologies have been developed to monitor the level of endogenous CO in biosystems. Among them, the fluorescence detection technology based on the fluorescent probe has the advantages of high sensitivity, excellent selectivity, simple operation, especially non-invasive damage to biological samples, and the possibility of real-time in situ detection, etc., which is considered to be one of the most effective and applicable detection techniques. Therefore, in the last few years, a lot of work has been carried out on the design, synthesis and in vivo fluorescence imaging studies of CO fluorescent probes. Furthermore, using fluorescent probes to detect the changes in CO concentrations in living cells and tissues as well as in organisms has been one of the hot research topics in recent years. However, it is still a challenge to rationally design CO fluorescent probe with excellent optical performance, structural stability, low background interference, good biocompatibility, and excellent water solubility. Therefore, this review focuses on the research progress of CO fluorescent probes in the detection mechanism and biological applications in recent years. However, this popular and leading topic has rarely been summarized comprehensively to date. Thus, the research progress of CO fluorescent probes in recent years is reviewed in terms of their design concept, detection mechanism, and their biological applications. In addition, the relationship between the structure and performance of the probes was also discussed. More significantly, we hope that more excellent optical properties fluorescent probes for gaseous transmitter molecule CO detection and imaging will overcome the current problems of high biotoxicity and limited water solubility in future.

Activated Two-Photon Near-Infrared Ratiometric Fluorescent Nanoprobe for ONOO- Detection and Early Diagnosis and Assessment of Liver Injury.

Liver injury poses a serious threat to human health and growing evidence suggests that it is closely associated with a biomarker (peroxynitrite, ONOO-). Therefore, considering that the relationship of ONOO- levels with the occurrence and development of liver injury disease remains a challenge, an urgent need exists to develop a reliable and robust tool for its visual rapid diagnosis and assessment. Herein, a two-photon near-infrared (TP-NIR) ratiometric fluorescent nanoprobe (NTC) based on a fluorescence resonance energy transfer (FRET) strategy was designed, synthesized, and characterized, which had the advantages of good water solubility, low background interference, deep tissue penetration, and high imaging resolution. Specially, NTC was constructed by self-assembly of an alkynyl group of a small-molecule fluorescent probe (NR) via click chemistry grafting onto azide chitosan (natural polymeric nanomaterial). NR contained acceptor 1 (NIR fluorophore) and donor 3 (D-π-A structure of naphthalimide derivative fluorophore) with outstanding TP properties that could be activated by ONOO- for the ratiometric detection of ONOO-. Furthermore, in the presence of ONOO-, NTC exhibited a short response time (∼10 s) and high selectivity and sensitivity toward ONOO- with an excellent detection limit as low as 15.3 nM over other reactive oxygen/nitrogen species. Notably, NTC has been successfully employed for ONOO- detection and imaging in living HepG2 cells, liver injury mice tissues, and mice models with satisfactory results. Thus, the construction of this NTC nanoprobe can provide a robust molecule tool for enabling early diagnosis and assessment of liver injury in the future.

Rational construction of a new water soluble turn-on colorimetric and NIR fluorescent sensor for high selective Sec detection in Se-enriched foods and biosystems.

As a naturally occurring amino acid, selenocysteine (Sec) plays a key role in a variety of cellular functions and Se-enriched foods. In this work, a robust water soluble fluorescence turn-on near-infrared (NIR) sensor NIR-Sec was constructed for Sec detection over biothiols in Se-enriched foods. Specifically, NIR-Sec contains a readily prepared water soluble NIR dicyanoisophorone fluorophore and a well-known response-site 2,4-dinitrobenzenesulfonyl moiety with strong intramolecular charge transfer (ICT) effect to quench the fluorescence intensity of NIR fluorophore. Upon addition of Sec, the NIR dicyanoisophorone fluorophore was released and a bright red emission at 663 nm was observed. Moreover, NIR-Sec toward Sec exhibited rapid response time (∼1 min), a large stoke shift (183 nm), and high selectivity and sensitivity (LOD: 52 nM). Impressively, NIR-Sec was successfully employed to detect and image Sec in Se-enriched foods and shrimp, indicating NIR-Sec could provide a robust tool for investigating the role of Sec in complex real-food samples.

Molecular engineering-based a dual-responsive fluorescent sensor for sulfur dioxide and nitric oxide detecting in acid rain and its imaging studies in biosystems.

Sulfur dioxide (SO2) and nitric oxide (NO), known as sulfur oxides and nitrogen oxides, are toxic air pollutants and seriously threaten human health. Herein, for the first time, a robust dual-response fluorescent sensor CGT with two different emission fluorophores and dual well-known response-group for visual bisulphites (HSO3-) and nitrites (NO2-) detection was reported. Specifically, once CGT was incubated with HSO3- firstly, the color of the test solution changed to dark yellow with no-fluorescence emission, following added NO2-, the color of the test solution changed to yellow with a bright cyan emission. However, NO2- was added firstly, the color of the test solution changed to dark purple with a white emission, and then added HSO3-, the color of the test solution changed to yellow with a bright cyan emission. Furthermore, CGT showed high sensitivity and selectivity toward HSO3- and NO2- detecting with good detection limits as low as 20.17 nM and 4.14 nM, respectively. Impressively, CGT showed good detection capability in complex aqueous samples and was successfully used for the detection of HSO3- and NO2- in biosystems. Thus, the experimental results indicated CGT as a powerful novel visual detecting tool for HSO3- and NO2- detecting in complex acid rain and biosystems.

Molecular engineering for construction of a novel ONOO-- activated multicolor fluorescent nanoprobe for early diagnosis and assessing treatment of arthritis in vivo.

Early diagnosis and assessment of the therapeutic effect of arthritis requires a reliable bioanalytical method to quantitatively and selectively detect the biomarkers peroxynitrite (ONOO-) in inflammatory diseases. Compared with previously reported probes for the specific detection of ONOO-, molecular engineering based on ONOO--activated multicolor fluorescence nanoprobes will have the advantages of providing multi-channel information and be more suitable for bioimaging in multicomponent complex environments. Herein, for the first time, a fluorescent nanoprobe (CSU-FT) based on fluorescence resonance energy transfer (FRET), which can be activated by ONOO-, was constructed for multicolor fluorescence imaging, diagnosis and treatment of arthritis in inflammatory mice. Specifically, an energy transfer scaffold was constructed by conjugation of a near-infrared (NIR) xanthane fluorophore with a rhodamine B fluorophore and multicolor by ONOO--modulated, which was then grafted onto sodium chondroitin sulfate (CSNa) to form CSU-FT through self-assembly. This nanoprobe shows a fast response time (<20s), outstanding selectivity and excellent detection limits as low as 11.7 nM. Interestingly, CSU-FT has been successfully used for intracellular multichannel imaging of endogenous ONOO- production as well as for diagnosis and treatment in a mice model of arthritis with impressive results, revealing practical application in physiological and pathological connection between ONOO- and arthritis.

Double-site-based a smart fluorescent sensor for logical detecting of sulphides and its imaging evaluation of living organisms.

Thiophenol and hydrosulphite are a group of toxic environmental pollutants, which contaminate land, water and food exhibiting a serious risk to human health. Herein, we reported a xanthene dye-based sensor (DSF) with dual well-known response sites for visual detecting PhSH and HSO3-. Specifically, when DSF reacted with PhSH firstly, the color of the solution changed to blue with bright red fluorescence emission. After added with HSO3-, the color of the solution became yellow, and emitted yellow fluorescence signal. However, DSF was first added with HSO3-, the color of the solution changed to purple with no-fluorescence emission, and then PhSH was added, the color of the solution changed to yellow with a bright yellow fluorescence. Notably, DSF exhibited high sensitivity and selectivity for PhSH and HSO3- detection with a very low detection limits of 2.27 nM and 22.91 nM, respectively. More importantly, DSF could detect PhSH and HSO3- in water, real-food and biological systems. Therefore, the experimental results showed DSF as a robust new logical monitoring tool for the detection of PhSH and HSO3- in water, real-food samples and biological systems.

Hydraulic performance prediction and optimization of an engine cooling water pump using computational fluid dynamic analysis.

In current research, the hydraulic performance prediction and optimization of an engine cooling water pump was conducted by computational fluid dynamic (CFD) analysis. Through CFD simulation, the pump head, shaft power and efficiency for the original pump at volume flow rate 25 L/min and impeller rotating speed 4231 r/min were 3.87 m, 66.7 W and 23.09% respectively. For improving hydraulic performance, an optimization study was carried out. After optimization, four potential optimized designs were put forward. The efficiency of the optimized design No.1 for engine cooling water pump was nearly 6% higher than that of the original pump model; and the head of the optimized design No.2 for engine cooling water pump was 9% higher than that of the original pump model. Under the condition of maintaining the pump head and considering comprehensive improvement effect, the optimized design No.3 was considered as the best design and selected as the test case for validating the optimum design. The hydraulic performance predictions for this optimum engine cooling water pump agreed well with experimental data at design condition with relative discrepancies of 2.9% and 5.5% for the pump head and pump efficiency, respectively. It proved that performance prediction calculation model and the automatic optimization model were effective. This research work can provide theoretical basis for the design, development and optimization of engine cooling water pump.

Rational Development of a New Reaction-Based Ratiometric Fluorescent Probe with a Large Stokes Shift for Selective Detection of Bisulfite in Tap Water, Real Food Samples, Onion Tissues, and Zebrafish.

Bisulfite (HSO3-) is usually widely added to tap water and food because it has antibacterial, bleaching, and antioxidant effects. However, its abnormal addition would cause a series of serious diseases related to it. Therefore, development of an effective method for HSO3- detection was of great significance to human health. In this work, a new reaction-based ratiometric fluorescent probe KQ-SO2 was rationally designed, which could be used for the highly selective detection of HSO3- in tap water, real food samples, onion tissues, and zebrafish. Specifically, a positively charged benzo[e]indolium moiety and a carbazole group through a condensation reaction resulted in KQ-SO2, which displayed two well-resolved emission bands separated by 225 nm, fast response (1 min), and high selectivity and sensitivity toward HSO3- upon undergoing the Michael addition reaction, as well as low cytotoxicity in vitro. In addition, KQ-SO2 has been successfully applied for the detection of HSO3- in tap water, real food samples, onion tissues, and zebrafish with satisfactory results. We predict that KQ-SO2 could be used as a powerful tool to reveal the relationship between HSO3- and the human health.