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Mapping the self-organization and spatial distribution of membrane proteins is key to understanding their function. Developing methods that can provide insight into correlations between membrane protein colocalization and interactions is challenging. We report here on a correlated stochastic optical reconstruction microscopy/homoFRET imaging approach for resolving the nanoscale distribution and oligomeric state of membrane proteins. Using live cell homoFRET imaging of carcinoembryonic antigen-related cellular adhesion molecule 1, a cell-surface receptor known to exist in a complex equilibrium between monomer and dimer/oligomer states, we revealed highly heterogeneous diffraction-limited structures on the surface of HeLa cells. Furthermore, correlated super-resolved stochastic optical reconstruction microscopy imaging showed that these structures comprised a complex mixture and spatial distribution of self-associated carcinoembryonic antigen-related cellular adhesion molecule 1 molecules. In conclusion, this correlated approach provides a compelling strategy for addressing challenging questions about the interplay between membrane protein concentration, distribution, interaction, clustering, and function. [ABSTRACT FROM AUTHOR]

The catalytic generation of H 2 in living cells provides a method for antioxidant therapy. In this study, an [FeFe]-hydrogenase mimic [Ru + Fe 2 S 2 @F127(80)] was synthesized by self-assembling polymeric pluronic F-127, catalytic [Fe 2 S 2 ] sites, and photosensitizer Ru(bpy) 3 2+. Under blue light irradiation, hydrated protons were photochemically reduced to H 2 , which increased the local pH in living cells (HeLa cells). The generated H 2 was subsequently used as an antioxidant to decrease reactive oxygen species (ROS) levels in living cells (HEK 293T, HepG2, MCF-7, and HeLa cells). Our findings revealed that the proliferation of HEK 293T cells increased by a factor of about six times, relative to that of other cells (HepG2, MCF-7, and HeLa cells). Intracellular ROS and pH levels were then monitored using fluorescent cell imaging. Our study showed that cell imaging can be used to evaluate the ability of Ru + Fe 2 S 2 @F127 to eliminate oxidative stress and prevent ROS-related diseases. [Display omitted] • An [FeFe]-hydrogenase mimic was synthesized for H 2 photogeneration. • The catalytic generation of H 2 was evaluated in HEK 293T cells. • The H 2 generated by Ru + Fe 2 S 2 @F127(80) was able to decrease ROS levels. • Light irradiation of Ru + Fe 2 S 2 @F127(80) led to an increase in intracellular pH. [ABSTRACT FROM AUTHOR]

Native broken-rice starch was used to create starch nanoparticles (StNPs) with particle sizes ranging from 100 nm to 800 nm. The fluorescent isothiocyanate poly- l -lysine StNPs (FITC-PLL-StNPs) were created in two steps. First, the StNPs were electrostatically modified by poly- l -lysine (PLL) molecules rich in amino acids. Second, fluorescein isothiocyanate reacted with some amino groups on PLL molecules (FITC). Fluorescence spectrophotometry was used to determine the degree of substitution (DS) and fluorescent properties of fluorescent starches. The study found that FITC-PLL-StNP-200 has higher fluorescence stability, more phagocytic cells, and a better and clearer fluorescence detecting effect than FITC-PLL-St, FITC-PLL-StNP-100, FITC-PLL-StNP-400, and FITC-PLL-StNP-800. The biological evaluation results showed that FITC-PLL-StNP-200 did not affect the viability of HeLa cells at the lysosome labeling concentration. These findings suggest that FITC-PLL-StNP-200 has strong and stable fluorescence, indicating that FITC-PLL-StNP-200 can be used as a fluorescent probe and lysosome marker in a variety of applications, particularly in biomedicine. [Display omitted] • Fluorecent starch nanoparticles (StNP) were synthesized. • FITC-PLL-StNP-200 has clearer fluorescence detecting effect. • FITC-PLL-StNP-200 has higher phagocytic amount of Hela cells. • FITC-PLL-StNP-200 is safe and possesses excellent biocompatibility. [ABSTRACT FROM AUTHOR]

[Display omitted] • Synthesis of indole dyes with good fluorescence properties to enhance the fluorescence of drugs and solve the problem of visualization therapy. • Water-soluble nido -carborane was introduced to solve the problem of poor water solubility of carborane. • Encapsulation with sodium alginate and different types of acrylic resins to improve drug biocompatibility and control the rate of slow drug release in vivo. • Tumor cell imaging shows that both the complexes INS-A and INS-C are able to enter the cell and are distributed within the cell. • The results of cell proliferation toxicity assay shows that both INS-A and INS-C have inhibitory effects on cancer cells. In this experiment, by combining water-soluble nido -carborane with indole dyes, and used non-toxic and non-irritating sodium alginate and acrylic resin as coating materials to obtain four fluorescent complexes, indol- nido -carborane-sodium alginate- Polymer-A (INS-A) 、indol- nido -carborane-sodium alginate-Polymer-B (INS-B)、indol- nido -carborane-sodium alginate-Polymer-C (INS-C) and indol- nido -carborane-sodium alginate-Polymer-D (INS-D).The transmission electron microscopy (TEM) results showed that the four complexes have different morphologies, with INS-A showing irregular clusters, INS-B being uniformly spherical, INS-C demonstrating a cashew-nut shape and INS-D manifesting a semi-encapsulated state. The spectroscopic properties and in vitro release experiments of the four complexes were performed in different simulated gastrointestinal environments. The results indicated that INS-A and INS-C had excellent photophysical properties and high cumulative release, so INS-A and INS-C were selected for subsequent experiments. Atomic Force Microscope (AFM) test manifested that the surfaces of INS-A and INS-C were relatively smooth. Imaging of HeLa cells with different channels was performed, the Pearson correlation coefficients of both INS-A and INS-C could be calculated to be distributed between 0.21 and 0.60, indicating that the complexes exhibited good imaging performance and could enter the cell and distribute around the nucleus. The results of cell proliferation toxicity (CCK8) experiments showed that at the concentration of 125 μg/mL, the inhibition rates of INS-A and INS-C on HCT-116 and HeLa cells were 47.15 %, 36.70 % and 42.81 %, 35.52 %, respectively, demonstrating that the complexes had an inhibitory effect on cancer cells. In summary, the fluorescent complexes prepared in this paper have good imaging ability and tumor targeting, and are potential fluorescent anticancer reagent. [ABSTRACT FROM AUTHOR]

The first difunctional probe H-1 for detecting ONOO− and Zn2+ at the same time showed high selectivity, good anti-interference capability, lower detect limit and short response time to them. [Display omitted] • · A new difuctional probe H-1 for ONOO− and Zn2+ detection at the same time was obtained firstly. • ·H-1 showed good selectivity and strong anti-interference ability for detecting ONOO− and Zn2+. • ·H-1 could fast response to ONOO− and Zn2+ in 15 s. • ·H-1 was used to monitor the ONOO− and Zn2+ level in living cells. Peroxynitrite (ONOO−) is one of the most significant reactive oxygen species (ROS) in living cells. Zn2+ in living cells plays an essential part in different physiological processes. The abnormal concentration of ONOO− and Zn2+ in living cells are related to many kinds of diseases, such as anemia, epilepsy, diarrhea, Alzheimer's disease, and so on. The relationship of ONOO− and Zn2+ in living cells when the relative disease occurs remains unknown. So we develop the first probe H-1 for detecting ONOO− and Zn2+ at the same time. The probe H-1 shows high selectivity, good anti-interference capability, low detection limit and short response time to ONOO− and Zn2+. When the probe was applied to detect ONOO− and Zn2+ in HeLa cells, we could observe the fluorescence changing in the green and blue channels separately without interference in real time. It has the potential to employ the relation of ONOO− and Zn2+ in some disease mechanism research. [ABSTRACT FROM AUTHOR]

Nitroreductase (NTR) is overexpressed in hypoxic tumor cells, which is closely related to inflammation, tumorigenesis, tumor invasion and metastasis. Therefore, developing fluorescence probes for detecting intracellular NTR sensitivity has great significance for diagnosis and treatment of tumors. Therefore, we designed a novel fluorescent probe (Pro-CN) based on julolidine skeleton for the detection of NTR. The probe could discriminate rapidly NTR from other biological species like sulfhydryl compounds and some ions. Meanwhile, a fine linear relationship between fluorescence intensity of the probe and NTR consistence has been observed with a very low detection limit of 4.4 ng/mL. In addition, Pro-CN was successfully applied in imaging endogenous NTR in Hela cells and living zebrafish. The excellent performance of the probe makes it have great potential for monitoring NTR in complex biological systems, and it also provides the possibility of its application in human health, disease diagnosis and treatment. [Display omitted] • Probe Pro-CN exhibits a turn-on fluorescence for sensing NTR. • Pro-CN is highly sensitive to sense NTR with a very low detection limit of 4.4 ng/mL. • Pro-CN was successfully applied for imaging endogenous NTR in living Hela cells and zebrafish. [ABSTRACT FROM AUTHOR]

Detecting and neutralizing Pd2+ ions are a significant challenge due to their cytotoxicity, even at low concentrations. To address this issue, various chemosensors have been designed for advanced detection systems, offering simplicity and the potential to differentiate signals from different analytes. Nonetheless, these chemosensors often suffer from limited emission response and complex synthesis procedures. As a result, the tracking and quantification of residual palladium in biological systems and environments remain challenging tasks, with only a few chemosensing probes available for commercial use. In this paper, a straightforward approach for the selective detection of Pd2+ ions is proposed, which involves the design, synthesis, and utilization of a propargylated naphthalene-derived probe (E)-N'-((2-(prop-2-yn-1-yloxy)naphthalen-1-yl)methylene)benzohydrazide (NHP). The NHP probe exhibits sensitive dual-channel colorimetry and fluorescence Pd2+ detection over other tested metal ions. The detection process is performed through a catalytic depropargylation reaction, followed by an excited state intramolecular proton transfer (ESIPT) process, the detection limit is as low as 11.58 × 10−7 M under mild conditions. Interestingly, the resultant chemodosimeter adduct (E)-N'-((2-hydroxynaphthalen-1-yl)methylene)benzohydrazide (NHH) was employed for the consecutive detection of CN− ions, exhibiting an impressive detection limit of 31.79 × 10−8 M. Validation of both detection processes was achieved through 1H nuclear magnetic resonance and density functional theory calculations. For real-time applications of the NHP and NHH probes, smartphone-assisted detection, and intracellular detection of Pd2+ and CN− ions within HeLa cells were studied. This research presents a novel naphthalene derivative for visually detecting environmentally toxic Pd2+ and CN− ions. The synthesized probe selectively binds to Pd2+, forming a chemodosimeter. It successfully detects CN− ions through colorimetry and fluorimetry, offering a low detection limit and quick response. Notably, it's the first naphthalene-based small molecule to serve as a dual probe for toxic analytes - palladium and cyanide. Moreover, it effectively detects Pd2+ and CN− intracellularly in cancer cells. [Display omitted] • Probe NHP selectively detects Pd2+ and forms chemodosimeter adduct NHH , showing a specific turn-on response to CN- ions. • The "off-on-off" ESIPT process led to the dual-channel detection of Pd2+ and CN− in an ethanol-H 2 O solution. • Consecutive detection, first of Pd2+ and then of CN-, showed naked-eye visibility, rapid response, and a low detection limit. • The study explored both on-site smartphone-based detection and intracellular detection of Pd2+ and CN- within HeLa cells. [ABSTRACT FROM AUTHOR]

Mercury (Hg) is one of the most widespread pollutants that pose serious threats to public health and the environment. People are inevitably exposed to Hg via different routes, such as respiration, dermal contact, drinking or diet. Hg poisoning could cause gingivitis, inflammation, vomiting and diarrhea, respiratory distress or even death. Especially during the developmental stage, there is considerable harm to the brain development of young children, causing serious symptoms such as intellectual disability and motor impairments, and delayed neural development. Therefore, it's of great significance to develop a specific, quick, practical and labor-saving assay for monitoring Hg2+. Herein, a mitochondria-targeted dual (excitation 700 nm and emission 728 nm) near-infrared (NIR) fluorescent probe JZ-1 was synthesized to detect Hg2+, which is a turn-on fluorescent probe designed based on the rhodamine fluorophore thiolactone, with advantages of swift response, great selectivity, and robust anti-interference capability. Cell fluorescence imaging results showed that JZ-1 could selectively target mitochondria in HeLa cells and monitor exogenous Hg2+. More importantly, JZ-1 has been successfully used to monitor gastrointestinal damage of acute mercury poisoning in a drug-induced mouse model, which provided a great method for sensing Hg species in living subjects, as well as for prenatal diagnosis. [Display omitted] • An activated probe JZ-1 for fluorescent detecion of Hg2+ was devised. • JZ-1 has dual NIR excitation and emission analysis wavelengths (both > 700 nm). • JZ-1 has a rapid response time and outstanding detection limit. • It was successfully used to in a drug-induced mouse of acute mercury poisoning. [ABSTRACT FROM AUTHOR]

[Display omitted] • A phenothiazine coumarin based fluorescent probe (WX-Lyso) for the detection of ClO– was synthesized. • WX-Lyso displayed a low LOD (0.99 µm) and rapid responsive time to ClO– (<5 s). • WX-Lyso was proved successfully has good lysosomal-targeting and imaging abilities to ClO– in Hela cells. A new phenothiazine coumarin based probe WX-Lyso for detection of ClO– was developed. The probe showed obvious aggregation-induced emission (AIE) characteristic and exhibited a highly selective and sensitive turn-on fluorescence signal at 544 nm for ClO– with a large Stokes shift of 144 nm. The limit of detection (LOD) of ClO– was measured as low as 0.99 μM and a good line equation was obtained in the 0–50 μM concentration range. The detection mechanism was elucidated FT-IR, ESI-MS analysis and DFT. Furthermore, the probe had been demonstrated successfully has good lysosomal-targeting and high-contrast imaging abilities, which has the potential to become a new chemical tool and provide help for detecting ClO– in living systems. [ABSTRACT FROM AUTHOR]

[Display omitted] • Ratiometric fluorescent probe for detecting H 2 S. • NIR emission wavelength and high energy transfer efficiency. • Excellent sensitivity and selectivity. • Achieving the detection of exogenous and endogenous H 2 S in living cells. Hydrogen sulfide is an important signaling molecule which plays a vital role in many biological processes. In this work, a novel near-infrared FRET (fluorescence resonance energy transfer) fluorescent probe was developed based on the rhodol derivative to detect H 2 S. The ratio of fluorescent intensity with the concentration of H 2 S exhibited an excellent linear relationship when probe LT responded to H 2 S. Probe LT exhibited excellent selectivity, sensitivity and anti-interference. LT was applied to sense endogenous and exogenous H 2 S in cells with great performance. Moreover, LT had the ability to target endoplasmic reticulum (ER) in Hela cells. [ABSTRACT FROM AUTHOR]

[Display omitted] • Based on dicyanoisophorone skeleton a near-infrared fluorescent probe was prepared and used to detect CO with high selectivity. • Two emission channels ratiometric fluorescence changes can be observed through adjusting the ICT effect of probe by CO. • The design of the probe enables it to be used for detecting CO in lysosomal subcellular organelles and further validated through cell co-localization imaging experiments. • The probe can be used to detect the endogenous and exogenous CO in Hela cells and could be used in living mice. • The probe is capable of detecting endogenous and exogenous CO through cell imaging experiments and has been successfully used in living mice. Carbon monoxide (CO) as an endogenous gas signaling molecule possesses important physiological functions and is of great significance in the treatment of various diseases. Real-time tracking of CO in living organisms has become a research hotspot in recent years. This article presents a lysosomal targeted near-infrared ratio fluorescence probe (TBM-CO) for selective detection of CO based on the dicyanoisophorone skeleton and morpholine fragment. The probe TBM-CO with weak ICT effect can be transformed to precursor TBM-NH 2 with strong ICT effect by the traditional Tsuji-Trost reaction procession in the presence of Pd2+ ions. The mechanism was proved by DFT calculation or the MS and HPLC results respectively. In the near-infrared region an obvious ratio fluorescence intensity change (F 686 / F 616) is observed in vitro spectral experiments. The concentration titration experiments indicate that there is a good liner relationship between the ratio fluorescence intensity and the concentration in the range of 0 to 50 μM (R2 = 0.996) and the detection limit is calculated as 0.38 μM. The cell fluorescence imaging and co-localization experiments further demonstrate that TBM-CO is able to detect the exogenous and endogenous CO in lysosomal subcellular organelle. Finally, it was used to detect the changes of CO concentration in living mice successfully. In short, a probe with three advantages of near-infrared emission, ratiometric fluorescence and organelle targeting was reported and used to detect CO successfully in cells and in living mice. [ABSTRACT FROM AUTHOR]

[Display omitted] • A new fluorescent probe CSH based on carbazole-thiophene was synthesized for the detection of ClO−. • CSH exhibits specific recognition of ClO− in the UV and fluorescence spectra, with detection limits as low as 3.61 × 10−6 mol/L and 1.16 × 10−6 mol/L. • Probe CSH can not only realize the detection of real water samples, but also can be applied to the detection of exogenous ClO− in HeLa cells. A carbazole thiophene-aldehyde and 4-methylbenzenesulfonhydrazide conjugate CSH was synthesized by introducing 5-thiophene aldehyde at the 3-position of the carbazole group as the precursor and then condensing it with 4-methylbenzenesulfonhydrazide. CSH has high selectivity and sensitivity towards ClO−, which can specifically identify ClO− by UV–Vis and fluorescence spectroscopy. CSH can rapidly respond to ClO− in the physiological pH range through a fluorescence quenching pattern, accompanied by the color of CSH changing markedly from turquoise to yellowish green under the 365 nm UV light. Probe CSH exhibits a quantitative response to ClO− (0–11 μM) with a low detection limit (1.16 × 10−6 M). Cell imaging experiments have shown that CSH can capture fluorescent signals in the cyan and yellow channels of HeLa cells through fluorescence confocal microscopy, and can successfully identify exogenous ClO− in HeLa cells. In addition, probe CSH can also be used to detect ClO− in environmental water samples. These results indicate that CSH has potential application prospects in the environmental analysis and biological aspects. [ABSTRACT FROM AUTHOR]

[Display omitted] • Water-soluble near-infrared QDs enable precise detection of intracellular copper ions with exceptional selectivity and sensitivity. • Low cytotoxicity and high biocompatibility of QDs ensure safe intracellular imaging applications. • Fluorescence bursts in response to changing copper ion content demonstrate QDs' excellent cellular imaging capabilities. • Synthesized QDs demonstrate stable and selective performance for precise quantification of copper content in biological systems. • This research contributes to understanding the physiological role of intracellular copper ions and advances biomedical imaging techniques. The detection and imaging of intracellular copper ions (Cu2+) play a crucial role in understanding their physiological implications and their involvement in various cellular processes. This study focuses on the synthesis and characterization of water-soluble near-infrared fluorescent CIS/ZnS core–shell quantum dots (QDs) with excellent biocompatibility and stability. The QDs exhibit exceptional selectivity and sensitivity for Cu2+ detection, allowing for precise quantification of Cu2+ content within biological systems. Furthermore, Co-incubation of the QDs with HeLa cells demonstrates their impressive cellular imaging capabilities, facilitated by fluorescence bursts in response to changing Cu2+ content. Overall, our proposed QDs are of great significance in advancing the research and application of near-infrared semiconductor quantum dots in biomedicine, and their near-infrared fluorescence properties and high fluorescence quantum yield (34.48 %) make them very advantageous for the precise detection of intracellular Cu2+ and cell fluorescence imaging. This research contributes to the understanding of copper ion dynamics within cells and opens avenues for further exploration of its role in cellular physiology. [ABSTRACT FROM AUTHOR]

[Display omitted] • Rare earth-doped carbon dots with aggregation-induced emission (AIE) for enhanced fluorescence. • Y-CDs exhibit bright yellow fluorescence upon water addition and UV light exposure. • Y-CDs show sensitivity to temperature and pH changes, with stable fluorescence intensity reduction. • Y-CDs enable specific imaging of the nucleus in HeLa cells for targeted cellular imaging. • Y-CDs demonstrate safety and efficiency in imaging zebrafish embryos for extended durations, offering potential for long-term vertebrate or ocular imaging. Carbon dot (CDs) materials are typically hindered by aggregation-caused quenching (ACQ) effect. However, there are limitations in terms of their development and application. The introduction of aggregation-induced emission (AIE) characteristics into CDs has emerged as a viable solution to this challenge. In this work, we synthesized a novel yellow fluorescence (FL) rare earth-doped AIE CDs (named Y-CDs), which integrate the benefits of AIE materials, rare earth materials, and CDs. Y-CDs exhibit bright yellow FL, good temperature sensitivity and pH response properties. In cell imaging, Y-CDs showed excellent targeting capability towards the nuclear in HeLa cells. Y-CDs also showed excellent biocompatibility and safety in imaging of zebrafish embryos and zebrafish. Even on the 10th day following culture of zebrafish embryos, the digestive system and lens of zebrafish can be accurately located and imaged. The work presented here suggests the great potential of replacing commercial dyes with Y-CDs for highly specific nuclear labeling and bioimaging. [ABSTRACT FROM AUTHOR]

In this manuscript, we designed and synthesized a fluorescent probe HBA based on caffeic acid for detecting Al3+ and HPO 4 2− by the mode of "off-on-off". The probe HBA can be utilized as a powerful method for the sequential recognition of Al3+ and HPO 4 2– in biological samples. [Display omitted] • A new dual-functioned fluorescent probe HBA based on caffeic acid was synthesized. • The new fluorescent probe HBA can sequential detect Al3+ and HPO 4 2–− with good selectivity and excellent sensitivity. • The probe HBA has good performance for detection of Al3+/HPO 4 2– in HeLa cells. In this work, we focused on synthesizing a new fluorescent probe HBA based on caffeic acid for detecting Al3+/HPO 4 2− by the mode of "off-on-off". HBA alone exhibited a weak fluorescence emission in aqueous solution. When Al3+ was added into the HBA solution, a significant green fluorescence was found at 498 nm. However, the introduction of HPO 4 2− to the solution of [ HBA -Al3+] complex induced the disappearance of green fluorescence. The detection limit of HBA was calculated as low as 41.7 nM for Al3+ and 62.1 nM for HPO 4 2−, respectively. Probe HBA exhibited good cell-membrane penetrability and had the potential to trace Al3+/HPO 4 2− in biological systems. [ABSTRACT FROM AUTHOR]

[Display omitted] • Lysosome-targeted carbon dots (L-CDs) were synthesized from hematoxylin. • The L-CDs have been used to visually recognize Hg2+ and SO 3 2− by smartphone. • The L-CDs have been employed to differentiate Hg2+ and SO 3 2− in living cells. Smartphone-assisted visual assay not only expands quantitative analysis but also enhance real-time on-site sensing capabilities. Herein, lysosome-targeted dual-emissive carbon dots (L-CDs) can not only recognize Hg2+ and SO 3 2− by ratiometric fluorescence and ratiometric absorption, but also visually quantify Hg2+ and SO 3 2− by smartphone-assisted method. With monitoring of intrinsic ratiometric fluorescent variation (I 580 /I 468), L-CDs are developed as an effective sensing platform for ratiometric fluorescent successive identification of Hg2+ and SO 3 2− accompanying with continuous fluorescence variation of blue, purplish pink, pink, and light yellow. With detecting of inherent ratiometric absorption change (A 538 /A 206), L-CDs are also constructed as an efficacious sensing terrace for ratiometric absorption consecutive discrimination of Hg2+ and SO 3 2−. More crucially, integrating continuous fluorescence color change and color recognizer APP in the smartphone, visual quantification of Hg2+ and SO 3 2− can be accomplished on the basis of the ratio of red value and blue value (R/B) with linear ranges of 0–130 and 0–850 µM, respectively, as well as LOD of 8.4 and 12.9 nM, respectively. More interestingly, confocal fluorescent imaging of HeLa cells further verifies that L-CDs can be regarded as favorable biosensors for on-site, real-time differentiation of Hg2+ and SO 3 2− in vitro and in vivo with ratiometric manners. [ABSTRACT FROM AUTHOR]

We have previously shown that exposure to TiO 2 nanoparticles (NPs) reduces the resistance of HeLa cells to bacterial infection. Here we demonstrate that the increased infectivity is associated with enhanced asymmetry in the cholesterol distribution. We applied a live cell imaging method which uses tunable orthogonal cholesterol sensors to visualize and quantify in-situ cholesterol distribution between the two leaflets of the plasma membrane (PM). In the control culture, we found marked transbilayer asymmetry of cholesterol, with the concentration in the outer plasma membrane (OPM) being 13 ± 2-fold higher than that in the inner plasma membrane (IPM). Exposure of the culture to 0.1 mg/mL of rutile TiO 2 NPs increased the asymmetry such that the concentration in the OPM was 51 ± 10 times higher, while the total cholesterol content increased only 21 ± 2%. This change in cholesterol gradient may explain the increase in bacterial infectivity in HeLa cells exposed to TiO 2 NPs since many pathogens, including Staphylococcus aureus used in the present study, require cholesterol for proper membrane attachment and virulence. RT-PCR indicated that exposure to TiO 2 was responsible for upregulation of the ABCA1 and ABCG1 mRNAs, which are responsible for the production of the cholesterol transporter proteins that facilitate cholesterol transport across cellular membranes. This was confirmed by the observation of an overall decrease in bacterial infection in ABCA1 knockout or methyl-β-cyclodextrin-treated HeLa cells, as regardless of TiO 2 NP exposure. Hence rather than preventing bacterial infection, TiO 2 nanoparticles upregulate genes associated with membrane cholesterol production and distribution, hence increasing infectivity. A great deal of work has been done regarding the toxicology of the particles, especially focusing on detrimental outcomes associated with reactive oxygen species (ROS) production. In this paper we show unambiguously a very surprising result, namely the ability of these particles to enhance bacterial infection even at very small exposure levels, where none of the deleterious effects of ROS products can yet be detected. Using a new imaging technique, we are able to demonstrate, in operando, the effect of the particles on cholesterol generation and distribution in live HeLa cells. This paper also represents the first in a series where we explore other consequences of increased membrane cholesterol, due to particle exposure, which are known to have multiple other consequences on human tissue function and development. [Display omitted] [ABSTRACT FROM AUTHOR]

[Display omitted] Carbon quantum dots (CQDs) with an average diameter of 3 nm, exhibiting blue photoluminescence, have been obtained from commercial conductive carbon black by a cost-effective and straightforward exfoliation method using dry ball milling in the presence of sodium carbonate. As a secondary abrasive medium, sodium carbonate provides effective exfoliation of carbon black with a high degree of CQD graphitization and plays an essential role in the functionalization of CQDs with oxygen groups. Due to the low toxicity of CQDs against HeLa cancer cells (cell viability above 90% at a CQD concentration of 200 μg cm−3) and the ability to penetrate cells and emit blue light, CQDs are possibly suitable for biological imaging of cells. [ABSTRACT FROM AUTHOR]

[Display omitted] • A triphenylamine based molecular probe (TPOH) is synthesized. • TPOH exhibits an extremely low toxic to HeLa cell. • TPOH has good prospects for biological and practical applications. • TPOH has the advantages of sensitive, rapidly response and low detection limit to the detection of Zn2+. A triphenylamine-based Schiff base (TPOH) was synthesized as a good fluorescent sensor for recognizing of Zn2+. The fluorescence intensity of the probe TPOH was significantly enhanced after coordination with Zn2+ with a yellow fluorescence at the excitation wavelength of 525 nm. In MeOH-H 2 O (3:7 in v/v) solution, the probe showed excellent selectively for Zn2+ over most other competing ions, which exhibited an Intramolecular Charge Transfer (ICT) mechanism in the recognition procedure. The reaction stoichiometry of 1:1 between TPOH and Zn2+ was determined based on the Job's plot and 1H NMR spectra, respectively. The HeLa cells maintained over 95 % of viability after 24 h exposure to TPOH, which identified the extremely low toxic of TPOH and can be used for in vivo cell imaging. [ABSTRACT FROM AUTHOR]

Complexes formed by combining pentacyclic triterpenes (PTs) with Aggregation-Induced Emission luminogens (AIEgens), termed pentacyclic triterpene-aggregation induced emission (PT-AIEgen) complexes, merge the chemotherapeutic properties of PTs with the photocytotoxicity of AIEgens. In this study, we synthesized derivatives by connecting three types of triphenylamine (TPA) pyridinium derivatives with three common pentacyclic triterpenes. Altering the connecting group between the electron donor TPA and the electron acceptor pyridinium resulted in increased production of reactive oxygen species (ROS) by PT-AIEgens and a red-shift in their fluorescence emission spectra. Importantly, the fluorescence emission spectra of BA-3, OA-3, and UA-3 extended into the near-infrared (NIR) range, enabling NIR-AIE imaging of the sites where the derivatives aggregated. The incorporation of the pyridinium structure improved the mitochondrial targeting of PT-AIEgens, enhancing mitochondrial pathway-mediated cell apoptosis and improving the efficiency of chemotherapy (CT) and chemo-photodynamic combined therapy (CPCT) both in vivo and in vitro. Cellular fluorescence imaging demonstrated rapid cellular uptake and mitochondrial accumulation of BA-1 (−2, −3). Cell viability experiments revealed that BA-1 (−2), OA-1 (−2), and UA-1 (−2) exhibited superior CT cytotoxicity compared to their parent drugs, with BA-1 showing the most potent inhibitory effect on HeLa cells (IC 50 = 1.19 μM). Furthermore, HeLa cells treated with BA-1 (1 μM), BA-2 (1.25 μM), and BA-3 (1 μM) exhibited survival rates of 2.99 % ± 0.05 % μM, 5.92 % ± 2.04 % μM, and 2.53 % ± 0.73 % μM, respectively, under white light irradiation. Mechanistic experiments revealed that derivatives induced cell apoptosis via the mitochondrial apoptosis pathway during both CT and CPCT. Remarkably, BA-1 and BA-3 in CPCT inhibited cancer cell proliferation in an in vivo melanoma mouse xenograft model. These results collectively encourage further research of PT-AIEgens as potential anticancer agents. PT-AIEgens BA-3 permeates cell membranes and accumulates in mitochondria, and subsequently triggers tumor cell apoptosis through the mitochondrial pathway in the absence or presence of light. [Display omitted] • Synthesizing nine PT-AIEgen fluorescent derivatives with AIE properties. • PT-AIEgens efficiently enter HeLa cells and specifically target mitochondria. • Developing a combined anticancer therapy based on CT of PTs and PDT of AIEgens. • Inducting synergistically apoptosis via mitochondrial pathway in vivo and vitro. [ABSTRACT FROM AUTHOR]

• 5-Methyl-2-phenyl-1,2,3-triazole-5-hydrazid (PT) was synthesized by "click chemistry". • A new Schiff base of 1,2,3-triazole (PTSB) was satisfactory for detecting Al3+. • PTSB was applied to image Al3+ in HeLa cells with a lower cytotoxicity. A new compound, 5-methyl-2-phenyl-1,2,3-triazole-5-hydrazid (PT) was designed and synthesized based on "click chemistry". The fluorescence probe 5-methyl-2-phenyl-1,2,3-triazole-5-hydrazid Schiff base (PTSB) was further constructed by a chemical reaction between PT and 4-(diethylamino) salicylaldehyde. PTSB could be used to determine Al3+ in EtOH with high sensitivity and strong anti-interference performance by fluorescence and UV–vis spectroscopic methods. The limit of detection to Al3+ is 5.84 nM and it showed an obvious solvatochromic effect under ultraviolet light. Furthermore, the sensing mechanism of PTSB detecting Al3+ was confirmed in the form of planar structure and 1:1 complexation ratio based on MS, Job's plot, 1H NMR titration, DFT calculation, and the single-crystal structure of PTSB, respectively. PTSB showed less low cytotoxicity to HeLa cells and was successfully used for chromatic bioimaging Al3+ in HeLa cells. It is expected to be developed and utilized as a fluorescence probe for detecting Al3+ in vivo. [Display omitted] [ABSTRACT FROM AUTHOR]

[Display omitted] • Chemosensor was configured by attaching responsive group, diaminomaleonitrile, to BODIPY scaffold. • Cu2+ can be selectively recognized on a 2-s time-scale. • The recognition mechanism is based on the Cu2+ induced intramolecular oxidative cyclization of γ-aminoimine. • The absolute fluorescence quantum yield of BD + Cu2+ is determined to be 98%, attributing to the formation of dicarbonitrile substituted imidazole ring. A highly fluorescent Cu2+-responsive sensor, 2-amino-3-(BODIPYmethyleneamino)maleonitrile (BD) was constructed by attaching diaminomaleonitrile to a BODIPY scaffold. Cu2+ can be selectively recognized on a 2-s time-scale by way of fluorescence emission. When Cu2+ and BD coexist in solution, typical BODIPY emission was observed and the emission intensity could be increased to 334 times that of the blank dye solution. The mechanism of fluorescence increase is based on the generation of highly fluorescent species by Cu2+-triggered oxidative cyclization of the attached diaminomaleonitrile. The absolute fluorescence quantum yield (AFQY) of the cyclization product is 98% determined by integrating sphere. The highly emissive character can be attributed to the imidazole ring and dicarbonitrile on the BODIPY scaffold. It surpasses the meso -phenyl substituted analogue in AFQY and detection limits (DL). The specific Cu2+ recognition behavior was also validated in Hela cells with high-contrast fluorescence images. [ABSTRACT FROM AUTHOR]

Nowadays, one of the most important reasons of death in the world is cancer. With the development of nanotechnology, advanced methods for treatment of cancer have introduced. In this work, the fluorescent carbon dots (CDs) were prepared from chitosan as the second abundant polysaccharide present in the nature. The surface of CDs was modified with chitosan (CDs/CS) and then the amino groups of chitosan were conjugated with activated folic acid (CDs/CS-FA) for controlled delivery of doxorubicin (DOX) as anticancer drug against HeLa cancer cells. The DOX loading efficiency of fluorescent CDs/CS-FA was high and nearly 60 %. Due to pH sensitive swelling/deswelling of CS, the percentage of cumulative DOX release could reach 90 % at cancer tissue (pH of 5.0) and 52 % at normal tissue (pH of 7.4) within 30 h. The cytotoxicity study revealed that the synthesized CDs were highly compatible on HeLa cells with cell viability 97–88 %. Cellular imaging shows that the entry of CDs/CS-FA to HeLa cells causes a green fluorescence, while the CDs/CS without FA have a negligible fluorescence. These results are due to the important role of FA in cell internalization. Thus, the CDs/CS-FA nanocarrier is suitable candidate for controlled pH sensitive drug delivery and cellular imaging. • The fluorescent carbon dots were synthesized by thermal decomposition and functionalized further with chitosan and folic acid. • The loading efficiency of anticancer drug (doxorubicin, DOX) into CDs/CS-FA nanocarrier was approximately 60%. • The drug release is pH responsive and could reach 90% at tumor tissue (pH 5.0) and 52% at normal tissue (pH 7.4) within 30h. • DOX loaded CDs/CS-FA displayed anticancer activity at low concentration of 4 μg/ml. • CDs/CS-FA nanocarrier was found to be highly compatible on HeLa cells and was used as fluorescent probes for the bio-imaging. [ABSTRACT FROM AUTHOR]

Bio-enzymes have the advantages of strong substrate specificity, high catalytic efficiency, and minimal toxic side effects, making them promising drugs in cancer therapy. However, the poor stability and cellular penetrability of uncoated protein in the physiological environment severely restricts the direct application of Bio-enzyme. To address it, we report a metal-organic framework (MOF), Hf-DBA (H 2 DBA, biphenyl carboxylic acid ligands). The morphology of the Hf-DBA was revealed by TEM and the diameter was in the range of 200 to 350 nm. Hf-DBA acted a carrier for intracellular delivery and protection of horseradish peroxidase (HRP). The prepared HRP@Hf-DBA can catalyze the excess H 2 O 2 in the tumor cells to generation of •OH for chemodynamic therapy (CDT). Compared with free HRP, the catalytic activity of HRP@Hf-DBA is significantly improved, and the optimal catalytic conditions are explored. The catalytic stability of HRP@Hf-DBA remained above 70% after 12 cycles of catalysis. After treatment with HRP@Hf-DBA, the apoptosis rates of A549 and Hela cells was 71.64%, and 76.86%. The results in vitro show that HRP@Hf-DBA can effectively inhibit the growth of tumor cells through enhanced CDT. We constructed a MOF (Hf-DBA) using biphenyl carboxylic acid ligands (H 2 DBA) and Hf4+ clusters, which employed as the carrier to immobilize horseradish peroxidase (HRP) for chemodynamic therapy. [Display omitted] • Hf-DBA was synthesized and used as a carrier for intracellular delivery and protection of horseradish peroxidase (HRP). • Hf-DBA displays excellent protection of HRP at high temperature and different pH. • HRP@Hf-DBA can catalyze the excess H 2 O 2 for chemodynamic therapy, showing good apoptosis induction of A549 and Hela cells. [ABSTRACT FROM AUTHOR]

[Display omitted] • Probe FBC-DS performed sufficient selectivity, fast response time, high sensitivity and a large Stokes shift to HClO. • FBC-DS was applied for imaging of exogenous and endogenous HClO in living HeLa cells and zebrafish with satisfactory performances. • FBC-DS was applied for corroborating that HClO could be an efficient marker for APAP-induced hepatotoxicity in the mice liver injury models. Drug-induced liver injury (DILI), as a classic acute inflammation, has attracted widespread concern due to its unpredictability and severity. Among the various reactive oxygen species, HClO has been used as a marker for the detection of DILI process. Thus, we designed and synthesized a "turn-on" fluorescent probe FBC-DS by modifying 3'-formyl-4'-hydroxy-[1,1'-biphenyl]-4-carbonitrile (FBC-OH) with N, N-dimethylthiocarbamate group for sensitively sensing HClO. Probe FBC-DS showed a low detection limit (65 nM), fast response time (30 s), an enormous Stokes shift (183 nm) and 85-fold fluorescence enhancement at 508 nm in the detection of HClO. Probe FBC-DS could monitor exogenous and endogenous HClO in living HeLa cells, HepG2 cells and zebrafish. In addition, probe FBC-DS has been successfully utilized in biological vectors for imaging acetaminophen (APAP)-induced endogenous HClO. Moreover, DILI caused by APAP is evaluated by probe FBC-DS through imaging over-expression of endogenous HClO in the mice liver injury models. All in all, we have every reason to believe that probe FBC-DS can be a potential tool to study the complex biological relationship between HClO and drug-induced liver injury. [ABSTRACT FROM AUTHOR]

[Display omitted] • Silver-mediated CDs as a red emissive probe (RCDs@Ag+) for the selective detection of intracellular GSH with LOD of 0.12 μM. • The almost 100% recovery of quenched fluorescence in addition to GSH, without interference for cysteine and homocysteine. • RCDs@Ag+ found effective in discriminating between normal and cancer cells. Glutathione (GSH) serves as a significant cancer-related biomarker that plays a pivotal role in preserving intracellular homeostasis. However, the structural and functional similarities between GSH and other biothioles (cysteine and homocysteine), make it difficult to distinguish GSH from them. In this study, we have developed a novel fluorescent probe utilizing silver-mediated red emissive carbon dots (RCDs@Ag+) for the discrimination of cancer cells from normal cells through the bioimaging of glutathione (GSH). The fluorescence intensity of RCDs is quenched significantly upon the addition of Ag+ (50 µM) and is recovered 95 % with the identical concentration of added GSH, without such effect occurring in cysteine and homocysteine. The fluorescence lifetime of the RCDs was found to be approximately 7.022 ns and the quantum yield was determined to be approximately 9.24 %. Further, RCDs@Ag+ are suitable for selectively detecting intracellular GSH due to their excellent biocompatibility, and low toxicity in normal NIH3T3 and HeLa cells. Most significantly, RCDs@Ag+ may be used as an excellent approach to spot cancer cells overexpressing GSH. [ABSTRACT FROM AUTHOR]

The successful synthesis of organoboron complexes with novel core structures facilitates the development of new functional dyes. In this context, synthesizing stable seven-membered organoboron complexes poses substantial challenges, so dyes of this type have seldom been studied. The successful synthesis of a series of pyrrole hemithioindigo-derived organoboron complexes is reported. The photophysical properties have been analyzed, and the results have been compared to those predicted by rigorous theoretical calculations. The presence of a seven-membered ring N,O boron-chelated moiety in these complexes was definitively confirmed by single crystal X-ray diffraction studies. Confocal laser experiments demonstrated the ability of one of the complexes studied to effectively permeate HeLa cells and selectively stain the cytoplasmic region. The reported synthetic strategy provides a framework for synthesizing a wide range of versatile organoboron dyes and opening up new avenues for developing innovative materials. [Display omitted] • Pyrrole hemithioindigo-derived organoboron complexes were designed and fully characterized. • Theoretical calculations were employed to disclose the structure-property relationships. • Cellular imaging of the dye was studied by confocal laser imaging. [ABSTRACT FROM AUTHOR]

Novel zinc porphyrins (trans -A 2 B 2 and A 3 B type) are reported containing pharmacophoric groups derived from Sorafenib at the meso -positions. The pharmacophoric and bioisosteric modification of Sorafenib was done with 2-methyl-4-nitro- N -phenylaniline. The in-vitro photo-cytotoxicity studies of zinc porphyrins on HeLa cells revealed excellent PDT based autophagy inhibition of cancer cells, with IC 50 values between 6.2 to 15.4 μM. The trans -A 2 B 2 type zinc porphyrin with two bioisosteric groups gave better cytotoxicity than A 3 B type. Molecular docking studies revealed excellent binding with mTOR protein kinase of the designed porphyrins. The confocal studies indicated significant ER localization of trans -A 2 B 2 type zinc porphyrin in HeLa cells along with ROS generation. trans -A 2 B 2 type zinc porphyrin induced ER stress in cancer cells, thereby causing elevation of Ca+2 ions in cytoplasm, which led to cancer cell death via autophagy pathway. The studies suggested that trans -A 2 B 2 and A 3 B type zinc porphyrins can be developed as theranostic agents for anti-cancer applications. Novel zinc porphyrins with pharmacophoric group at their meso -positions have been synthesized. Zinc porphyrins showed ER localization in HeLa cells and induced cell death via autophagy pathway. [Display omitted] • Novel zinc porphyrins having Sorafenib inspired pharmacophoric unit were synthesized. • Zinc porphyrins exhibited excellent photocytotoxicity against cancer cells. • Live cell imaging showed co-localization of zinc porphyrins in the ER. • These porphyrins caused ER stress via ROS generation in the cancer cells. • These porphyrins induced autophagy in the cancer cells through ER stress mechanism. [ABSTRACT FROM AUTHOR]

A multifunctional fluorescent probe with "ESIPT+AIE" properties were synthesized. Three mental ions including Pb2+, Ag+ and Fe3+ could be selectively recognized and distinguished and remarkable fluorescence enhancement was observed. [Display omitted] • 1. A multifunctional fluorescent probe with "ESIPT + AIE" properties was synthesized. • 2. Pb2+, Ag+ and Fe3+ ions could be selectively recognized and distinguished with remarkable fluorescence enhancement. • 3. The probe had been successfully applied to water sample detection, test paper experiment and biological cell imaging. In this work, three Schiff-based fluorescent probes with aggregation-induced emission (AIE) and excited intramolecular proton transfer (ESIPT) characters were synthesized by grafting 2-aminobenzothiazole group onto 4-substituted salicylaldehydes. More important, a rare tri-responsive fluorescent probe (SN-Cl) was developed by purposeful variation of substituents in the molecule. It could selectively identify Pb2+, Ag+ and Fe3+ in different solvent systems or with the help of masking agent and show complete fluorescence enhancement without interference of other ions. Meanwhile, the other two probes (SN-ON and SN-N) could only recognize Pb2+ in DMSO/Tris-HCl buffer (3: 7, v/v, pH = 7.4). According to Job's plot, density functional theory (DFT) calculations and NMR analysis, coordination between SN-Cl and Pb2+/Ag+/Fe3+ was determined. The LOD values for three ions were as low as 0.059 μM, 0.012 μM and 8.92 μM, respectively. Ideally, SN-Cl showed satisfactory performance in real water samples detection and test paper experiments for three ions. Also, SN-Cl could be used as an excellent imaging agent for Fe3+ in HeLa cells. Therefore, SN-Cl has the ability to be a "single fluorescent probe for three targets". [ABSTRACT FROM AUTHOR]

Hypochlorous acid (HClO) is a vital bioactive molecule. Abnormal levels of HClO can affect the body's immune system and pathological processes, leading to many diseases such as kidney disease and neurodegenerative diseases. Therefore, it is very important and necessary to develop a rapid and sensitive HClO detection method. In this work, we propose a novel phenothiazine-xanthene fluorophore, which has flexible adjustability and outstanding responsiveness to HClO. Using phenothiazine-xanthene fluorophore, a "turn-on" probe 7-ethyl-1,2,3,7-tetrahydrochromeno[2,3- b ]phenothiazine-4-carbaldehyde (PTZ-CHO) was designed and synthesized for the trace analysis of HClO. In the presence of HClO, the sulfur atom on phenothiazine is rapidly oxidized to the sulfoxide, and a significant fluorescence enhancement (about 100-fold) was observed. Moreover, the advantages including fast response (<10 s), ultra-high sensitivity (limit of detection = 6 nM), strong specificity, and splendid light stability can all be achieved by PTZ-CHO. Benefitting from these advantages, this unique HClO-responding probe has been successfully applied to the detection of HClO in Hela cells, RAW 264.7 cells, and environmental water samples. [Display omitted] • A novel phenothiazine-xanthene fluorophore PTZ-CHO was first synthesized. • PTZ-CHO has fast response time (<10 s) and high sensitivity (LOD = 6 nM) to HClO. • PTZ-CHO shows 100-fold fluorescence enhancement after responding to HClO. • PTZ-CHO was employed for imaging of exogenous and endogenous HClO in living cells. • PTZ-CHO was applied to the detection of HClO in real water samples. [ABSTRACT FROM AUTHOR]

With the promising biosafety and favorable cell imaging efficiency, silicon quantum dots (SiQDs) was broadly exploited as non-viral gene carriers in recent years. However, the low transfection efficiency and weak targeting ability hindered its further clinical applications. In this study, the combined plasma membrane coating and cluster bombing strategy was adopted to enhance the gene delivery potential of silicon quantum dots nanoclusters (SiNC). Initially, SiNC was generated via 3, 3′-Dithiodipropionic acid (DipA) crosslinking of SiQDs, then the obtained nanoclusters were coated by distinct plasma membrane. Interestingly, cell membrane coated SiNC (CM-SiNC) underwent particle size change, the typical character of "cluster bombing", when exposed to high GSH concentration, which was observed in the tumor microenvironment. Meanwhile, CM-SiNC can be efficiently uptaken by HEK 293T and HeLa cells, therefore transferring DNA into those cells. More importantly, among the particles coated by HeLa (HeLa-M), Red Blood (RBC-M) or RAW267.4 (RAW-M) cell membrane, HeLa cell membrane coating exhibited better cellular uptake and transfection efficiency in HeLa cells, which suggested the encouraging tumor targeting ability. In sum, these data suggested that cluster bombing of SiNC could be beneficial for physical stability and biodistribution, the additional plasma membrane coating further endowed SiNC the efficient gene delivery and tumor targeting ability. Therefore, CM-SiNC had the potential as a gene delivery vector and its application should be further addressed in vivo. [Display omitted] • The combined plasma membrane coating and cluster bombing strategy was adopted to enhance the gene delivery potential of SiNC. • CM-SiNC exhibited the responsive capacity to the high GSH level tumor environment. • SiNC coated by tumor cell membrane endows the nanoparticles the homologous properties of the source cells. • In addition to carrying genes, CM-SiNC/DNA can act as tracers. [ABSTRACT FROM AUTHOR]

Due to the favorable stability, water solubility and good biocompatibility, carbon dots have attracted much attention. Herein, a novel nitrogen-doping bifunctional carbon dots (N-BCDs) with ultra-highly quantum yield (QY abs = 70.4%) is prepared through microwave-assisted method. 50 μg/mL of N-BCDs emit intense fluorescence in HeLa and GES-1 cells with negligible cytotoxicity. In addition, effective inhibition of N-BCDs to human insulin (HI) fibrillation is observed even at 10:1 (mass ratio of HI: N-BCDs) by ThT fluorescence, CD assay and TEM. N-BCDs prevent HI from fibrillation with prolonged lag time and reduced fluorescent intensity at equilibrium, regardless of the addition time of N-BCDs (HI: N-BCDs = 1:1, mass ratio), which has been rarely reported before. Furthermore, the morphology of final HI fibrils is shorter and thinner in the presence of N-BCDs. Mechanism studies reveal that the enhanced hydrogen bond between HI monomers and N-BCDs inhibits nucleation during the lag stage (K a : 1.54 × 104 L·mol−1, 298 K), while the accumulation of N-BCDs blocks the growth of profibrils in the elongation stage. To the best of our knowledge, it's the first time to observe the accumulation of N-BCDs around HI profibrils with TEM. Our study provides a new strategy for developing efficient nanoparticle inhibitors for protein fibrillation. Unlabelled Image [ABSTRACT FROM AUTHOR]

The nitrogen and sulfur co-doped carbon dots (NSCDs) were synthesized using cysteine as precursor by hydrothermal approach, which showed good aqueous solubility, high fluorescent quantum yield (QY = 38.7%) and good photostability. The experiments with cells demonstrated that NSCDs possessed excellent biocompatibility and their cytotoxicity was low (cell viability ≥90%) in both normal and cancer cell lines. Furthermore, NSCDs as fluorescent probes could be used for the imaging of cells, which showed a good membrane permeability and strong resistance to photobleaching. In addition, the cellular uptake of NSCDs presented a time-dependent saturation. The imaging applicability of NSCDs in different cancer cells (MCF-7, A375, Hela and U251 cells) has also been demonstrated. Therefore, NSCDs are considered as promising candidates for the design of low cytotoxicity bioimaging agents and a cellular location system based on fluorescence measurements. Unlabelled Image • NSCDs show well-dispersed, high QY of 38.7% and good photostability. • NSCDs possess excellent biocompatibility in normal and cancer cell lines. • NSCDs are as fluorescent probes for cancer cell imaging and locating • The cellular uptake of NSCDs presents a time-dependent saturation. . [ABSTRACT FROM AUTHOR]

This study examined the efficiency of pH-dependent, fluorescent carbon dots for the sensing of hazardous anions in aqueous media and cell imaging. The nitrite anion, an important water-soluble element for environmental and biological systems, requires continuous monitoring because a high concentration can affect the systems severely. The as-synthesized carbon dots efficiently detected the nitrite anion in aqueous solution through a fluorescent 'Turn Off' phenomenon. The quenching mechanism was investigated through proper microscopic and spectroscopic studies. The limit of detection and linear detection range were 7.9 nM and 2.3μM-7.7 mM, respectively. The sensitivity was tested with different water samples. In a parallel experiment, the as-synthesized carbon dots were used as a cell-imaging probe for HeLa cells, highlighting their potential in different biological studies. Image 1 • Fluorescent nitrogen-doped carbon nanodots were synthesized using a facile green chemical pathway. • The as-synthesized carbon dots showed selective and sensitive nitrite ion detection. • The as-synthesized carbon dots exhibited high efficiency for cell imaging. [ABSTRACT FROM AUTHOR]

Abnormal levels of Cys, Hcy and GSH are associated with various diseases, thus monitoring biothiols is of great significance. In this work, a dual-emission responsive near-infrared fluorescent probe NIR-NBD for detecting Hcy and Cys/GSH was developed based on the conjugation of a dicyanoisophorone based fluorophore (NIR-OH) and 7-nitrobenzofurazan (NBD). To our surprise, the addition of Hcy induced significant fluorescence enhancement at both 549 and 697 nm; while Cys/GSH resulted in major fluorescence emission at 697 nm. The detection limit was determined to be 33.2 nM for Cys, 33.5 nM for Hcy, and 34.4 nM for GSH. Therefore, the probe can be used for discriminative detection of Hcy and Cys/GSH. Moreover, fluorescence imaging of HeLa cells indicated that the probe was cell membrane permeable and could be used for visualizing Hcy and Cys/GSH in living cells. Image 1 • A novel NIR fluorescent probe for discriminative sensing of Hcy and Cys/GSH in dual channel was developed. • The probe can measure Hcy level in serum samples. • The probe could sense intracellular Hcy and Cys/GSH in living HeLa cells. [ABSTRACT FROM AUTHOR]

A fluorescence-enhanced and lysosome-targeted Al3+ probe (1) based on a pyrazole-containing hydrazone was developed in this work. The fluorescent probe 1 displays an OFF–ON fluorescence response to Al3+ in the lysosome pH environment. In addition, the resultant 1 –Al3+ complex could act as an ON–OFF fluorescence sensor for F−. Fluorescence imaging shows that 1 is suitable for visualization of Al3+ in lysosomes of HeLa cells. Image 1 • A quite simple hydrazone-based fluorescent probe for Al3+ has been developed. • The probe displayed an OFF-ON response toward Al3+ in aqueous solution. • The resultant Al3+ complex of the probe could act as an on-off fluorescent sensor for F−. • The probe has been used for imaging of Al3+ in lysosomes of HeLa cells. [ABSTRACT FROM AUTHOR]

• Acetyl curcumin (AC) was synthesized from curcumin via hydrothermal method. • An electrospinning process has been employed for the preparation of all liposome nanoparticles. • Korsmeyer-Peppas (K-P) and Higuchi models were used for the kinetic studies. • Drug loaded PCSLNPs are exhibiting promising results towards sustain drug delivery applications. • The 20 μM IC 50 value was obtained from MTT assay for ACPCSLNPs in HeLa cells. Despite substantial advancements in divergent drug delivery systems (DDS), there is still room for novel and innovative nanoparticle-mediated drug delivery methodologies such as core/shell liposomes to deliver drugs in a kinetically controlled manner into the active site without any side effects. Herein, ((1E,6E)-3,5-dioxohepta-1,6-diene-1,7-diyl) bis (2-methoxy-4,1-phenylene) diacetate acetyl curcumin (AC)-loaded poly(lactic-co-glycolic acid) (PLGA) core/shell liposome nanoparticles (ACPCSLNPs) were prepared using an electron spray method under an applied electric field, which facilitated the uniform formation of nano-sized liposome nanoparticles (LNPs). Then, kinetically controlled and sustained drug release profiles were investigated using the as-prepared ACPCSLNPs. Moreover, the inner polymeric core could not only induce the generation of electrostatic interactions between the polymer and drug molecules but could also affect the prominent repulsions between the polar head groups of lipids and the nonpolar drug molecules. As a result, the sustained maximum release of the drug molecules (~48.5%) into the system was observed over a long period (~4 days). Furthermore, cell cytotoxicity studies were conducted in a human cervical cancer cell line (HeLa) and a healthy human dermal fibroblast cell line (HDFa) by employing all AC loaded LNPs along with free drugs. Multicolor cell imaging was also observed in HeLa cells using ACPCSLNPs. Notably, more curcumin was released from the ACPCSLNPs than AC due to the presence of polar group attractions and polar-polar interactions between the lipid head groups and curcumin since curcumin is more soluble than AC in aqueous medium. In addition, the predictions of the release kinetic patterns were also investigated thoroughly using the exponential-based Korsmeyer-Peppas (K-P) and Higuchi models for drug-loaded LNPs and PLGA NPs, respectively. [ABSTRACT FROM AUTHOR]

Aggregation-induced emission luminogens (AIEgens) provide a new approach to address the aggregation-induced quenching (ACQ) defect prevalent in traditional fluorescent dyes. Since there are only two dispersion forms of single molecule (monomer state, weak fluorescence) and aggregates (multimer state, strong fluorescence) in aqueous medium, most of the reported AIEgens exhibit a single emission band and therefore cannot be used for dual-channel fluorescence imaging in living cells. In this work, the "monomer-dimer-multimer" dispersion mechanism was innovatively introduced into the design of dual-emission AIEgens. Under the guidance of this concept, two cyanovinyl-pyrene dual-emission AIEgens with twisted molecular configuration have been readily synthesized and studied by theoretical calculations, UV–visible absorption, steady-state fluorescence, time-resolved fluorescence, dynamic laser scanning (DLS) and laser confocal imaging. These AIEgens emit weak fluorescence in monomer state due to intramolecular C C rotation. With gradual aggregation, they form dimer state to emit blue fluorescence centered at 460 nm, and then convert into multimer state to emit red fluorescence around 570 nm, simultaneously exhibiting AIE and dual-emission characteristics. They also have excellent photostability, good membrane permeability and low cytotoxicity. Confocal imaging tests demonstrate that AIEgens composed of cyanovinyl-pyrene and benzimidazole moieties is available for dual-channel imaging in Hela cells and macrophages cells, and shows great potential in designing ratiometric nanoprobe. Our design mechanism will provide a versatile platform for the development of dual-emission AIEgens. • "Monomer-dimer-multimer" dispersion mechanism was used to design dual-emission AIEgens. • Two dual-emission AIEgens were synthesized and studied. • They have excellent photostability, good membrane permeability and low cytotoxicity. • Cyanovinyl-pyrene-benzimidazole AIEgens show potential in dual-channel imaging and ratiometric sensing in cells. [ABSTRACT FROM AUTHOR]

• A dicyanoisophorone-based fluorescent probe was developed for sensing H 2 S with a large Stokes shift (155 nm). • The probe showed faster time response and high sensitivity for H 2 S. • The probe can be used to detect exdogenous and endogenous H 2 S in living HeLa cells. Due to the importance of hydrogen sulfide (H 2 S) in physiology and pathology, the development of fluorescence probes for the detection of H 2 S has attracted extensive attention of researchers. We developed a H 2 S fluorescence probe (DCN-S) based on dicyanoisopentanone using dithioether and ester groups as the reaction sites. Under the nucleophilic substitution of H 2 S, disulfide bond of DCN-S was broken. Then the probe changed into dicyanoisophorone derivative and emitted an orange fluorescence band from 530 nm to 700 nm (centred 580 nm). Upon response for H 2 S, DCN-S exhibited high sensitivity (88 nM detection limit) and large stokes shift (155 nm). Importantly, the probe also was successfully used for endogenous and exogenous imaging of living cells. [ABSTRACT FROM AUTHOR]

A quinoline-based fluorescence sensor QDTD was developed for Zn2+. QDTD can detect Zn2+ by fluorescence turn-on. Detecting limit (0.27 μM) of QDTD for Zn2+ was far below WHO standard (76.0 μM). For the practical application, compound QDTD could be used to determine Zn2+ in real samples and applied to the test kit. More importantly, QDTD was expertly applied for Zn2+ imaging in HeLa cells and zebrafish with good membrane-permeability. Detection mechanism of Zn2+ ion by compound QDTD was suggested through the analytical tools like 1H NMR titration, ESI-MS, Job plot, fluorescent and UV–vis titration, and theoretical calculations, and through the synthesis and applications of a model compound AAQA. Unlabelled Image • A highly selective fluorescent chemosensor QDTD for Zn2+ was designed and synthesized. • QDTD could detect Zn2+ by fluorescence turn-on with the low detection limit (0.27 μM). • Sensor QDTD was applied to the real water samples and test strip. • Sensor QDTD could successfully quantify Zn2+ in HeLa cells and zebrafish. [ABSTRACT FROM AUTHOR]

[Display omitted] • A fluorescent probe was synthesized based on benzopyran-chromone for detection of ONOO−. • The probe shows short response time for ONOO− (<30 s). • The probe shows specifically selectivity and a very low detection limit of 22.4 nM for ONOO−. • The probe can accurately identify endogenous and exogenous ONOO− in HeLa cells. Peroxynitrite is widely present in organisms and closely related to many pathophysiological functions. Therefore, it is of great physiological significance to develop capable probes for detecting ONOO−. In this work, a novel fluorescent probe B-Ch was designed based on the intramolecular charge transfer (ICT) effect. By means of molecular engineering, the replacement from diethylamine group to hydroxyl group has improved the detection sensitivity of the probe. After the addition of ONOO−, the solution color and fluorescence showed noticeable changes, which were visible to the naked eye. The probe showed excellent advantages: visualization, good selectivity, low sensitivity (22.4 nM), good stability and biocompatibility, exogenous and endogenous imaging of ONOO− in HeLa cells. [ABSTRACT FROM AUTHOR]

[Display omitted] • Borophene quantum dots are fabricated via liquid-phase exfoliation-assisted ultrasonication. • Borophene quantum dots exhibited blue fluorescence at 428 nm when excited at 370 nm. • Borophene quantum dots acted as a sensor for the detection of dehydroepiandrosterone biomarker. • Borophene quantum dots loaded cellulose paper used as a sensor for DHEA detection. • Cell imaging of Saccharomyces cerevisiae and MTT assay of HeLa cells were performed using borophene quantum dots. A novel fluorescence approach is introduced for sensing of dehydroepiandrosterone (DHEA). The primary characteristic of pediatric adrenocortical carcinoma disease causes due to the excessive production of DHEA, a hormone whose levels in the bloodstream can potentially facilitate the early diagnosis of cancer. In this paper, a water-dispersed borophene quantum dots (BQDs) based sensor was developed for the detection of DHEA, marking the first instance of such an application. The as-synthesized BQDs display blue fluorescence under 365 nm of UV light and exhibit λ Ex/Em at 370/428 nm with a good quantum yield of 24.12%. The as-prepared BQDs acted as a fluorescent "turn-on" sensor for the detection of DHEA with a dynamic range from 0.1 to 125 μM with the detection limit of 18.72 nM. The BQDs-based paper strip was designed for visual detection of DHEA. In addition, BQDs were utilized as imaging probes to visualize Saccharomyces cerevisiae cells. The developed method was extended for DHEA assay in biofluids (plasma and urine). [ABSTRACT FROM AUTHOR]

• Two new " turn off" chemosensor (V3 &V4) based on oxazolonaphthoimidazo[1,2- a ] pyridine has been synthesized. • V3 and V4 fluorescent probes shows high sensitivity and selectivity for detecting Fe3+ and DCP analytes. • For Fe3+, V3 and V4 undergo " turn-off " mechanism with the detection limit of 14.1 and 4.5 nM, respectively. • Vapour phase sensing of DCP. • Live cell imaging in HeLa cells. Two new turn-off fluorescent sensors (V3 and V4) presented in the article revealed the potential application for the precise detection of Fe3+ and diethylchlorophosphate (DCP). These sensors include oxazolonaphthoimidazo[1,2- a ]pyridine scaffold integrated with anthracene and pyrene-based framework. This design has facilitated the twisted intramolecular charge transfer (TICT) and planarised intramolecular charge transfer (PLICT) mechanisms, which were confirmed using computational and photophysical studies. The V3 and V4 fluorescent probes were particularly sensitive and highly selective for detecting Fe3+ and DCP analytes. For Fe3+, V3 and V4 undergo turn-off mechanism with the detection limit of 14.1 and 4.5 nM , respectively. Intracellular detection of Fe3+ via confocal live cell imaging was also demonstrated, showing its application under intracellular conditions. Our experimental data revealed the promises of V3 and V4 for instantaneous, accurate and on-spot monitoring of Fe3+ and DCP, even in the presence of other interfering analytes. [ABSTRACT FROM AUTHOR]

The red emission of upconversion nanoparticles (UCNPs) is located in an "optical window" range of the biological tissue, which has a promising prospect in biology application. In this work, novel red-emitting NaYF 4 :Yb3+/Er3+ UCNPs with CH 3 COO− modifications were synthesized by single-mode focused microwave method. The morphology, structure, and luminescence properties of as-prepared UCNPs were characterized. The results showed that single-mode focused microwave method was an effective approach to prepare hydrophilic and strongly red emission UCNPs within a drastically reduced reaction time (only 10 min) compared to the traditional methods. Importantly, we also demonstrated that the CH 3 COO− modified NaYF 4 :Yb3+/Er3+ UCNPs could be successfully applied for in vitro imaging of HeLa cells. This work not only provides a rapidly synthetic methodology for the preparation of red-emitting UCNPs but also offers an effective material for cancer cell imaging. • Red-emitting NaYF 4 :Yb3+/Er3+ UCNPs with CH 3 COO− modifications. • Application of UCNPs for imaging of HeLa cells. • Single-mode focused microwave method. • Preparation of UCNPs within short reaction time (only 10 min). [ABSTRACT FROM AUTHOR]

[Display omitted] • Nitrogen and bromine co-doped red fluorescence carbon dots (N,Br-CDs) with high QY were synthesized. • The multifunctional fluorescent sensors for off–on detection of Ag+ and glutathione were constructed based on N,Br-CDs. • The fluorescence sensor has been applied to the determination of Ag+ in environmental water samples. • Cellular imaging of Ag+ and glutathione was performed in HeLa cells by the N,Br-CDs. Carbon dots (CDs) with red fluorescence emission have excellent advantages in cell imaging. Herein, novel nitrogen and bromine doped CDs (N,Br-CDs) were prepared with 4-bromo-1,2-phenylenediamine as precursor. The N, Br-CDs present the optimal emission wavelength at 582 nm (λ ex = 510 nm) at pH 7.0 and 648 nm (λ ex = 580 nm) at pH 3.0 ∼ 5.0, respectively. The fluorescence intensity of N,Br-CDs at 648 nm versus Ag+ concentration shows a good relationship from 0 to 60 μM with the limit of detection (LOD) of 0.14 μM. Furthermore, the fluorescence of N,Br-CDs/Ag+ is efficiently restored via the combination of glutathione (GSH) and Ag+ and linearly changes with GSH concentration from 0 ∼ 6.0 μM with LOD of 49 nM. This method has been successfully employed to monitor intracellular Ag+ and GSH with fluorescence imaging. The results suggest that the N,Br-CDs has application potential in the sensing of Ag+ and visual monitoring of GSH in cells. [ABSTRACT FROM AUTHOR]

• A FRET-based probe presented showed selective and rapid detection of nitric oxide (NO) with LOD ∼1 nM. • The nitric oxide detection is assisted by Cu2+ ion, which in turn provide more specific detection. • The detection of NO with Cu2+ ion assistance constructs a molecular level security device. • High efficiency for NO detection in HeLa cells by dual channel (green/red), low cytotoxicity and high brightness. • The probe has dual fluorophores, FRET mechanism, smart device application and useful for NO detection in HeLa cells. A rhodamine-dansyl conjugate (RPD) has been synthesized for rapid FRET-based ratiometric detection of nitric oxide (NO) up to nM level mediated by the Cu2+ ions. The emission band of dansyl centered at 481 nm showed quenching upon addition of Cu2+ and further addition of NO, showed a decrease at dansyl emission band and ratiometrically generate a new band at 580 nm corresponding to the open spirolactam derivative of rhodamine. Subsequent chemical inputs of Cu2+ and NO generate a smart molecular level security device with a unique set of inputs to unlock the device. The rapid detection of NO is devoid of false signalling, as the detection is dependent on sequence-based two input correct combination. The [ RPD -Cu2+] solution was also highly efficient to detect NO in solution by a visual change in colour: i.e. colourless to pink and pale green to orange under naked eye and UV-light respectively. The probe-Cu2+ solution exhibits excellent NO imaging in HeLa cells with low cytotoxicity and the lower level of emission in the presence of probe-Cu2+ which is advantageous to see the initial incubation of probe inside the live cells. The applicability of [ RPD +Cu2+] has been proven by efficient detection of NO in HeLa cells by dual enhanced emissions in green /red channels. [ABSTRACT FROM AUTHOR]

Hydrogen sulfide (H 2 S) is a kind of gaseous signal molecule in many physiological processes. In order to detect H 2 S, a novel "turn on" fluorescent probe 6,12-dihydroxyperylene-1,7-dione (DPD) was designed and synthesized. The probe DPD is fluorescence silence, while the addition of H 2 S induces an obvious green fluorescence with an obvious color change from dark blue to yellow-green. The probe shows excellent selectivity, fast response (2.5 min) and linear curve (0–90 μM) in wide effective pH range (4–10). Competition experiments are also revealed in corresponding studies and the detection limit is 3.6 μM. The response mechanism is proved to be the reduction of the probe by H 2 S, which is confirmed by 1H NMR. Furthermore, through the fluorescence turn-on signal toward H 2 S in Hela cells, probe DPD was successfully applied to monitor H 2 S in living Hela cells. Unlabelled Image • A "turn-on" probe DPD for hydrogen sulfide was developed. • DPD shows highly selective and sensitive response to hydrogen sulfide. • DPD shows rapid response and high sensitivity toward hydrogen sulfide. • The response mechanism of the probe DPD with H 2 S was confirmed to be reduction of carbonyl groups to hydroxyl groups. • DPD can monitor the exogenous cysteine in solution and living cells. [ABSTRACT FROM AUTHOR]

Abstract Thiols such as amino acids Cys/Hcy and peptides GSH play vital roles in biological systems. Due to their similar structures and reaction activities, it is still desirable to develop new probes to simultaneously detect and discriminate Cys/Hcy and GSH. Taking advantage of the reductive activity of SH in these thiols, we combined two fluorophores coumarin and 7-nitrobenzofurazan with an ether bond to form the CA-NBD sensor to detect and discriminate Cys/Hcy and GSH simultaneously. CA-NBD showed high selectivity towards Cys/Hcy and GSH over other analytes with apparent colorimetric and fluorescent signals. At the excitation wavelength of 460 nm, CA-NBD could be used to discriminate Cys/Hcy from GSH with different fluorescence response. Furthermore, CA-NBD was successfully used to detect thiols in living Hela cells with low cytotoxicity. Graphical abstract A structurally simple and versatile fluorescent probe CA-NBD was synthesized, which could be used as a dual emission fluorescent probe for the detection and discrimination of Cys/Hcy and GSH in aqueous solution under mild conditions. Furthermore, the probe was successfully used to simultaneously detect Cys and GSH in living cells with low cytotoxicity. Image 1 Highlights • Coumarin and 7-nitrobenzofurazan were combined by an ether bond to form CA-NBD. • CA-NBD can be used as a naked-eye detector for biothiols over other amino acids. • CA-NBD can detect and discriminate Cys/Hcy and GSH simultaneously. • CA-NBD can be used to detect Cys in living cells with low cytotoxicity. [ABSTRACT FROM AUTHOR]

A highly Zn2+ ion responsive novel cation sensor (L) based on the dual mechanism (ESIPT/ICT) was designed, synthesized and characterized. The sensor L shows great turn on selectivity for Zn2+ ion in 1:1 stoichiometric manner via rapid color change and 5-fold fluorescence enhancement in CH 3 CN over other interfering cations. The addition of Zn2+ ion to L, triggers the deprotonation of imidolic and hydroxylic protons of L, which in turn shows an enhanced red shift in both UV–Vis and fluorescence spectra of the sensor. The limit of detection and binding constant obtained are well within those reported for Zn2+ ion. The theoretical calculations were correlated with experimental results to understand the sensing mechanism between host guest interactions and L distinguishes Zn2+ from Cd2+. Furthermore, bioimaging studies were undertaken to investigate practical usefulness of L to recognize Zn2+ ion using HeLa cells. • A cation sensor L was synthesized by simple condensation reaction. • Optical sensor (L) is highly selective for Zn (II) ion. • An L penetrate into HeLa cells and recognizes Zn (II) ion. • The cell viability of L was found to be 98.72%. • The L could be easily recyclable using suitable reagent. [ABSTRACT FROM AUTHOR]

Abstract A new fluorescent probe was designed and synthesized according to the photo-induced electron transfer theory (PET) and the results of density functional theory calculation. The synthesized probe had a larger Stokes shift (130 nm) and double emission peak in response to highly toxic thiophenols, which could be applied in rapid and high sensitive detection of thiophenol in aqueous solution. A 25-fold fluorescence intensity enhancement was achieved and the fluorescent intensity at 460 nm had a linear relationship to the thiophenol in concentration range of 0–2.0 μM. Furthermore, a remarkable detection limit (6 nM) could be achieved. 50-fold other species have no interference to the detection. The practical utility of the probe was demonstrated by live HeLa cells imaging and thiophenol detection in real water samples. In linear range of 0–2.0 μM, the probe showed good recoveries (from 95% to 108%) for thiophenol detection in natural water samples. This method possesses high sensitivity, lower detection limit and fast response (i.e., 10 min, which is shorter than the average time response of other reported methods), indicating that the synthesized probe would be promising for real-time detection of thiophenols. Graphical abstract fx1 Highlights • DFT calculations were used to design a thiophenol sensor and understand the mechanism. • A novel double emission fluorescent probe BIN-T was synthesized and characterized. • BIN-T possesses high fluorescence quantum yield and fast response to thiophenol. • The probe can be applied in thiophenol assay in real water samples and bioimaging. [ABSTRACT FROM AUTHOR]