Win-win integration: A mitochondria targeted AIE photosensitizer for hypochlorite detection and type I & type II photodynamic therapy.

BACKGROUND: Photodynamic therapy (PDT) is a pioneering and effective anticancer modality with low adverse effects and high selectivity. Hypochlorous acid or hypochlorite (HClO/ClO-) is a type of inflammatory cytokine. The abnormal increase of ClO- in tumor cells is related to tumor pathogenesis and may be a "friend" for the design and synthesis of responsive phototherapy agents. However, preparing responsive phototherapy agents for all-in-one noninvasive diagnosis and simultaneous in situ therapy in a complex tumor environment is highly desirable but still remains an enormously demanding task. RESULTS: An acceptor-π bridge-donor-π bridge-acceptor (A-π-D-π-A) type photosensitizer TPTPy was designed and synthesized based on the phenothiazine structure which was used as the donor moiety as well as a ClO- responsive group. TPTPy was a multifunctional mitochondria targeted aggregation-induced emission (AIE) photosensitizer which could quickly and sensitively respond to ClO- with fluorescence "turn on" performance (19-fold fluorescence enhancement) and enhanced type I reactive oxygen species (ROS) generation to effectively ablate hypoxic tumor cells. The detection limit of TPTPy to ClO- was calculated to be 185.38 nM. The well-tailored TPTPy anchoring to mitochondria and producing ROS in situ could disrupt mitochondria and promote cell apoptosis. TPTPy was able to image inflammatory cells and tumor cells through ClO- response. In vivo results revealed that TPTPy was successfully utilized for PDT in tumor bearing nude mice and exhibited excellent biological safety for major organs. SIGNIFICANCE AND NOVELTY: A win-win integration strategy was proposed to design a tumor intracellular ClO- responsive photosensitizer TPTPy capable of both type I and type II ROS production to achieve photodynamic therapy of tumor. This work sheds light on the win-win integration design by taking full advantage of the characteristics of tumor microenvironment to build up responsive photosensitizer for in situ PDT of tumor.

Tailoring plasmonic sensing strategies for the rapid and sensitive detection of hypochlorite in swimming water samples.

A tunable plasmonic sensor has been developed by varying the dextran content in the initially synthesized dextran-gold nanoparticle (dAuNPs) solution. A colloidal nanogold solution (dAuNPs-Sol) was initially prepared using dextran and gold salt in alkaline media by a one-pot green synthetic route. The dAuNPs-Sol was combined with varying amounts of dextran (ranging from 0.01 to 30.01%) to create a tunable probe, along with different solid formats, including tablet (dAuNPs-Tab), powder (dAuNPs-Powder), and composite (dAuNPs-Comp). Both the liquid and solid phase plasmonic probes were characterized using UV-vis spectroscopy, transmission electron microscopy (TEM) dynamic light scattering (DLS), and zeta potential analysis. The impact of dextran content in the dAuNP solution is studied in terms of surface charge and hydrodynamic size. The influence of operational treatments used to achieve solid dAuNPs probes is also explored. All plasmonic probes were employed to detect a broad range of OCl¯ concentrations (ranging from µM to mM) in water through aggregation followed by calculating a lower and upper limit of detection (LLoD, ULoD) of the proposed colorimetric sensors. Results indicate that the most sensitive detection is achieved with a lower dextran content (0.01%), which exhibits an LLoD of 50 µM. The dAuNPs-Sol sensor is selective and demonstrates real-world applicability, as confirmed by interference analysis and successful testing with various water samples. Additionally, it is found that a 20 × concentration of dextran-coated gold nanoparticles could be attained without any changes in the particle morphology. This concentration is achieved through a straightforward process that does not require the use of a centrifuge machine. This finding highlights the practicality and simplicity of the method, indicating its potential for scalable and cost-effective production of concentrated dAuNPs without compromising their structural integrity.

A novel thienothiophene-based "dual-responsive" probe for rapid, selective and sensitive detection of hypochlorite.

BACKGROUND: Hypochlorite/hypochlorous acid (ClO-/HOCl) is a biologically crucial reactive oxygen species (ROS), produced in living organisms and has a critical role as an antimicrobial agent in the natural defense system. However, when ClO- is produced excessively, it can lead to the oxidative damage of biomolecules, resulting in organ damage and various diseases. Therefore, it is imperative to have a straightforward, quick and reliable method for over watching the minimum amount of ClO- in different environments. RESULTS: Herein, a new probe TTM, containing thienothiophene and malononitrile units, was developed for exceptionally selective and sensitive hypochlorite (ClO-) detection. TTM demonstrated a rapid "turn-on" fluorescence response (<30 s), naked-eye detection (colorimetric), voltammetric read-out with anodic scan, low detection limit (LOD = 0.58 µM and 1.43 µM for optical and electrochemical methods, respectively) and applicability in detecting ClO- in real water samples and living cells. SIGNIFICANCE AND NOVELTY: This study represents one of the rare examples of a small thienothiophene-based molecule for both optical and electrochemical detections of ClO- in an aqueous medium.

A Commercially Available 2-aminoanthracene Fluorescent Probe for Rapid and Sensitive Detection of Hypochlorite in 100% Buffer Solution and its Application in Complex Water Samples.

Hypochlorite (ClO-), a crucial chemical in the living organism, engages in various physiological activities. However, high amounts of ClO- result in oxidative damage. In this work, a commercially available 2-aminoanthracene (AA) was used to detect ClO-. AA demonstrated distinct properties such as superior selectivity and rapid response (< 30 s) with a low detection limit (140 nM) towards ClO- in 100% buffer solution. Furthermore, the probe exhibited a notable achievement by effectively identifying the presence of ClO- in complicated water samples. In conclusion, AA offers an easy-to-use and accurate method for quantifying ClO- in complex water samples.

Bis-cyanostilbene based fluorescent materials: A rational design of AIE active probe for hypochlorite sensing.

In the present investigation cyanostilbene based molecular probes, PCS and PCO, bearing N,N-dimethylthiocarbamate and N,N-dimethylcarbamoyal groups, respectively, have been synthesised. These probes exhibit AIEE activity in their aggregated state in the mixed solvent system of THF: H2O by way of turning on their emission, which has also been observed in powder, neat thin films and hybrid polymer films. While the probe PCO is silent to ClO-, PCS exhibits a significant response towards ClO- rationalised on the basis of HOCl specific oxidation of thiocarbamate, which is also extended to detect ClO- in water samples. Additionally, applicability of the test strips of PCS for rapid on-site detection of ClO- has been demonstrated. The experimental results are supplemented by the theoretical calculations wherever possible.

Hypochlorous acid-activated near-infrared fluorescent probe for in vivo/exogenous detection and dairy toxicity evaluation.

Oxidative stress has been reported to be closely associated with many diseases, and an excessive overdose of hypochlorite (ClO-) can also induce stress-related diseases. In this study, we designed and synthesized a NIR probe, named W-1a based on computational analysis of DCM (4-(Dicyanomethylene)-2-methyl-6-(4-dimethylaminostyryl)-4H-pyran) derivatives for specific detection of ClO-. The probe exhibited dual fluorescence and colorimetric sensing with a response time of <1 min and a detection limit of 0.15 µM. Additionally, the probe was successfully applied for fluorescence imaging of ClO- at the cellular level and ebrafish endogenous/exogenous ClO- assay and dairy toxicity assessment. Thus, we present a potential method for developing an efficient and reliable detection of ClO- in early stage using near-infrared dyes.

A dual-responsive fluorescent turn-on sensor for sensitively detecting and bioimaging of hydrazine and hypochlorite in biofluids, live-cells, and plants.

Hydrazine (N2H4) and hypochlorite (ClO-) are extremely harmful to the public health, so it is vitally necessary to detect them in living system. Herein, we developed a new phenthiazine-thiobarbituric acid based dual-analyte responsive fluorescent sensor PT for visually distinguishing and detecting N2H4 and ClO-. PT underwent N2H4/ClO--induced CC breakage, achieving olive-drab/brilliant green fluorescence lighting-up response towards N2H4/ClO- with superb specifity, ultra-sensitivity (detection limit: 15.4 nM for N2H4, 13.7 nM for ClO-), and ultra-fast response (N2H4: <15 s, ClO-: <20 s). The mechanisms for sensing N2H4 and ClO- were investigated with support of spectral measurements and DFT investigation. Sensor based paper-strip/silica-gel device was developed for in-field supervision and on-site monitoring of gaseous and aqueous N2H4 and ClO- solution. In addition, the PT was also applied for quantitatively detecting N2H4 and ClO- in soil, food, plants and bio-fluids. Moreover, PT was utilized to visualize exogenous N2H4 and ClO- in living plants and live-cells, demonstrating this sensor utilized as a powerful tool to detect N2H4 and ClO- in biological fields.

3-Aminophenylboronic acid-functionalized molybdenum disulfide quantum dots for fluorescent determination of hypochlorite.

A simple method is reported for hypochlorite determination based on fluorescence 3-aminophenylboronic acid-functionalized molybdenum disulfide quantum dots (B-MoS2 QDs). B-MoS2 QDs with strong fluorescence at 380 nm have been successfully synthesized by the amidation reaction between APBA and hydrothermal MoS2 QDs. Hypochlorite sensing was proposed utilizing the fluorescent quenching effect of 3,3',5,5'-tetramethylbenzidine dihydrochloride (TMB) on B-MoS2 QDs and the fast redox reaction between hypochlorite and TMB. The fluorescent quenching effect of TMB to B-MoS2 QDs was proved to be caused by static dynamic quenching and inner filter effect. A good linear relationship was obtained in the hypochlorite concentration range from 1 to 20 µM, and the limit of detection (LOD) was 36.8 nM. The proposed fluorescent detection assay was simple and fast, taking only 5 min at room temperature. Satisfactory results were obtained in the standard spike recovery tests on tap water and milk samples, which indicate high potential in constructing fluorescent bio-detection assays.

Tetraphenylethylene-thiosemicarbazone based ultrafast, highly sensitive detection of hypochlorite in aqueous environments and dairy products.

We have designed and synthesised a novel fluorescent probe with a tetraphenylethylene (TPE) scaffold as an active fluorescent unit and thiosemicarbazide (TSC) group as a recognition unit. The probe, TPE-TSC, exhibited superior selectivity towards hypochlorite (ClO-) with a low limit of detection (2.0 nM). It also demonstrated a turn-off response for a brief period (<30 s) via an oxidation reaction. Furthermore, high-resolution mass spectrometry (HRMS) revealed that TPE-TSC reacted with ClO- by forming a carboxylic acid moiety in nearly 100% aqueous environments. More significantly, the probe detected ClO- in disinfectant, spiked milk samples, and spiked water samples. In all, TPE-TSC proposes an optimistic approach precisely for the determining the quality of milk and water contaminated with ClO- and trace amounts of ClO- in disinfectants.

Green-emitting carbon quantum dots as a dual-mode fluorescent and colorimetric sensor for hypochlorite.

In this work, green-emitting carbon quantum dots were successfully prepared through a facile one-step solid-state reaction method. The obtained green-emitting carbon dots (G-CDs) showed good fluorescence stability in NaCl aqueous solution and different pH values. Moreover, the G-CDs showed high sensitivity and selectivity for detecting hypochlorite by both fluorometry and colorimetry. Under the optimized condition, a highly sensitive detection of hypochlorite was established in the range of 0.2-100 µM and 10-150 µM for fluorescent and colorimetric methods, respectively. The corresponding limits of detection (LOD) were 0.0781 µM and 1.82 µM, respectively. Therefore, the G-CDs were successfully applied to determinate hypochlorite in actual water samples. In addition, a paper-based sensor loading with the G-CDs was also developed for rapid visual detection of hypochlorite. The results suggested that the G-CDs could be a promising candidate to detect hypochlorite.

A fluorescent sensor for selective detection of hypochlorite and its application in Arabidopsis thaliana.

Hypochlorite, as one of reactive oxygen species, has drawn much attention due to its essential roles in special biological events and disorders. The exogenous hypochlorite remains a risk for human, animals and plants. In this work, a novel water soluble quinolin-containing nitrone derivative T has been developed for fluorometric sensing hypochlorite. The response mechanism of T towards ClO- was reported for the first time. In comparison with the reported sensors for ClO-, the sensor T in this work exhibited advantages including high selectivity (80 fold over other analytes), rapid response (within 5 s) and lipid-water distribution transformation (LogP from 2.979 to 6.131). Further biological applications suggested that T was capable of monitoring both exogenous and endogenous ClO- in living cells. The imaging in Arabidopsis thaliana indicated that the absorption and transmission of ClO- in plant could be monitored by this sensor through the chlorine-related mechanism. This work might raise referable information for further investigations in the physiological and pathological events in both tumor and plants.

A dual-response ratiometric fluorescent probe for hypochlorite and hydrazine detection and its imaging in living cells.

In this work, a dual-response ratiometric fluorescent probe (E)-3-(5-(2-nitrovinyl)thiophen-2-yl)-9-phenyl-9H-carbazole (NTPC) for high selectivity and sensitivity detection of ClO- and N2H4 was successfully developed. This probe NTPC showed ratiometric fluorescent response to ClO- and N2H4, which induces obvious naked-eye color changes, respectively. In addition, the NTPC for ClO- and N2H4 detection displayed low detection limits of 71.4 nM and 0.6 µM, respectively. And the sensing mechanism of NTPC with ClO- and N2H4 was well confirmed by 1H NMR and HR-MS spectra. Moreover, this novel probe was applied to monitoring and differentiating ClO- and N2H4 in living cells, and exhibits good biocompatibility and low cytotoxicity.

A twist six-membered rhodamine-based fluorescent probe for hypochlorite detection in water and lysosomes of living cells.

A novel six-membered rhodamine-based fluorescent probe (6G-ClO) was developed from 2-formyl rhodamine (6G-CHO) and used for hypochlorite detection in water and HUVEC cells. Different from planar penta cycle of rhodamine spirolactam, there was a twist six-membered spirocyclic hydrazone in 6G-ClO optimized by Gaussian software at DFT/B3LYP/6-31G(d) level. The high selectivity, high sensitivity and fast response of 6G-ClO towards ClO- would be attributed to the twist six-membered spirocycle. Test-strip prepared with 6G-ClO was successfully used to semi-quantitatively indicate the concentration of ClO- in water. 6G-ClO can also quantitatively detect the concentration of ClO- in tap water and swimming pool water. The detection limit of 6G-ClO was as low as 12 nM. The co-localization staining of HUVEC cells further verified that 6G-ClO could specifically accumulate in lysosomes and capture exogenous/endogenous ClO- in living lysosomes. 6G-ClO would be a practical probe for real-time monitoring of ClO- in the biological and real water samples.

A novel pyridyl triphenylamine-BODIPY aldoxime: Naked-eye visible and fluorometric chemodosimeter for hypochlorite.

An aldoxime containing fluorescent probe based on vinylpydine-appended triphenylamine-BODIPY has been designed and used for hypochlorite detection. OX-PPA-BODIPY was developed by introducing an aldoxime group into the 2-position of BODIPY, which can be used for the detection of hypochlorite with a sharp color change from pink to green. The attachment of 4-vinylpyridine moiety to triphenylamine-BODIPY constructs a fluorogen with desirable conjugated system. The probe, which displays extremely weak fluorescence owing to the CN isomerization mechanism at 2-position of BODIPY, responds to HClO/ClO- through a dramatic enhancement of its fluorescence intensity. This new probe, a naked-eye visible and fluorometric chemodosimeter, exhibits high selectivity and sensitivity toward hypochlorite over other reactive oxygen species (ROS) and anions. The detection is accompanied by a 20-fold increase in fluorescent intensity (ΦF from 0.02 to 0.43). The detection limit of the probe for hypochlorite is 7.37×10-7M. Moreover, OX-PPA-BODIPY can be used to detect hypochlorite in real water samples.