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Nuclear RNA export into the cytoplasm is one of the key steps in protein expression to realize biological functions. Despite the broad availability of nucleic acid dyes, tracking and quantifying the highly dynamic process of RNA export in live cells is challenging. When dye-labeled RNA enters the cytoplasm, the dye molecules are released upon degradation of the RNA, allowing them to re-enter the cell nucleus. As a result, the ratio between the dye exported with RNA into the cytoplasm and the portion staying inside the nucleus cannot be determined. To address this common limitation, we report the design of a smart probe that can only check into the nucleus once. When adding to cells, this probe rapidly binds with nuclear RNAs in live cells and reacts with intrinsic H2S. This reaction not only activates the fluorescence for RNA tracking but also changes the structure of probe and consequently its intracellular localization. After disassociating from exported RNAs in cytoplasm, the probe preferentially enters lysosomes rather than cell nucleus, enabling real-time quantitative measurement of nuclear RNA exports. Using this probe, we successfully evaluated the effects of hormones and cancer drugs on nuclear RNA export in live cells. Interestingly, we found that hormones inhibiting RNA exports can partially offset the effect of chemotherapy.

An oligonucleotide-functionalized gold nanoparticle probe was developed and the high-efficiency detection of telomerase activity for cellular imaging toward the identification of tumors was realized.

The lysosome-targeting carbon dots (CDs) with excellent water solubility and strong blue emission were synthesized through a one-step functional modification for long-term lysosome imaging in living cells. Based on the carboxyl-rich CDs synthesized by oxidizing carbon black in refluxing HNO3, then N,N-dimethylethylenediamine (DMEDA) was chemically linked onto the CDs through acylation reaction to obtain DMEDA modified carbon dots (M-CDs). The infrared spectrum of M-CDs showed the characteristic peak of acylamide (O=C–NH–) at 1658 cm−1, indicating the successful modification of DMEDA. The quantum yield of M-CDs was 15.6%, which was 27 times higher than the initial carboxyl rich CDs, meeting the requirement of cell imaging. The probe entered cells through the temperature-dependent endocytosis way and the co-localization experiment with commercial dye Lyso-Tracker red showed that the probe localized in lysosomes and could be used as a universal lysosome tracker in different cell lines. Moreover, compared to commercially available Lyso-Tracker blue, M-CDs were more photostable under UV light. The fluorescence of M-CDs was still brightness after time-lapsed imaging by confocal microscopy for 120 min with an interval of 5 min in living cells, implying that the M-CDs could be used for long-term imaging of lysosomes.

A ratiometric fluorescent probe with a large emission shift was developed for the accurate measurement of hydrogen peroxide (H2O2) in sophisticated pyroptosis signaling pathways. The results reported here demonstrate that H2O2, as a principal member of ROS, is a critical upstream signaling molecule in regulating pyroptosis.

Understanding the biomolecular interactions in a specific organelle has been a long-standing challenge because it requires super-resolution imaging to resolve the spatial locations and dynamic interactions of multiple biomacromolecules. Two key difficulties are the scarcity of suitable probes for super-resolution nanoscopy and the complications that arise from the use of multiple probes. Herein, we report a quinolinium derivative probe that is selectively enriched in mitochondria and switches on in three different fluorescence modes in response to hydrogen peroxide (H2 O2 ), proteins, and nucleic acids, enabling the visualization of mitochondrial nucleoprotein dynamics. STED nanoscopy reveals that the proteins localize at mitochondrial cristae and largely fuse with nucleic acids to form nucleoproteins, whereas increasing H2 O2 level leads to disassociation of nucleic acid-protein complexes.

Stimulated emission depletion (STED) microscopy provides a powerful tool for visualizing the ultrastructure and dynamics of subcellular organelles, however, the photobleaching of organelle trackers have limited the application of STED imaging in living cells. Here, we report photostable and amphiphilic carbon dots (Phe-CDs) with bright orange fluorescence

Chemical sensing for the sensitive and reliable detection of mercury(II) ions (Hg

Endoplasmic reticulum (ER) is an important organelle of a membranous tubule network in cells for the synthesis, assembly, and modification of peptides, proteins, and enzymes. Autophagy and destruction of ER commonly occur during normal cellular activities. These processes have been studied extensively, but the spontaneous ER regeneration process is poorly understood because of the lack of molecular tools capable of distinguishing the intact, damaged, autophagic, and regenerative ER in live cells. Herein, we report a dual-localizing, environment-responsive, and lifetime-sensitive fluorescent probe for real-time monitoring ER autophagy and regeneration in live cells. Using this tool, the fluorescence lifetime imaging can quantitatively determine the degrees of ER destruction and spontaneous recovery. Significantly, we show that triglycerides supplied in lipid droplets can efficiently repair ER via the two critical pathways: (i) supplying materials for ER repair by converting triglycerides into fatty acids and diglycerides and (ii) partially inhibiting autophagy for stressed ER.

Understanding signaling molecules in regulating organelles dynamics and programmed cell death is critical for embryo development but is also challenging because current imaging probes are incapable of simultaneously imaging the signaling molecules and the intracellular organelles they interact with. Here, we report a chemically and environmentally dual-responsive imaging probe that can react with gasotransmitters and label cell nuclei in distinctive fluorescent colors, similar to the adaptive coloration of chameleons. Using this intracellular chameleon-like probe in three-dimensional (3D) super-resolution dynamic imaging of live cells, we discovered SO2 as a critical upstream signaling molecule that activates nucleophagy in programmed cell death. An elevated level of SO2 prompts kiss fusion between the lysosomal and nuclear membranes and nucleus shrinkage and rupture. Significantly, we revealed that the gasotransmitter SO2 is majorly generated in the yolk, induces autophagy there at the initial stage of embryo development, and is highly related to the development of the auditory nervous system.

Since the expression level of human telomerase RNA (hTR) in tumor cells is much higher than that in normal cells, the determination of hTR is of prime importance in biological research of tumors. In this work, we report molecular beacon-functionalized gold nanoparticles for hTR imaging in live cells. The molecular beacon has a loop-and-stem structure with hTR recognition sequences and a red fluorophore Cy5. In the presence of hTR, the hTR sequence could be hybridized with the loop of molecular beacon to form a duplex DNA chain and thus the fluorescence state switched from “off” to “on”. After co-incubation with cells, the probe could readily permeate into cells, leading to the in situ imaging of intracellular hTR. The proposed approach could be used to differentiate tumor cells from normal ones and assess hTR expression levels in different tumor cells. Furthermore, the proposed approach allowed us to dynamically monitor the expression level of hTR in live cells and holds great potential for application in tumor diagnosis and hTR-related drug delivery.

The dynamics of DNA and RNA structures in live cells are important for understanding cell behaviors, such as transcription activity, protein expression, cell apoptosis, and hereditary disease, but are challenging to monitor in live organisms in real time. The difficulty is largely due to the lack of photostable imaging probes that can distinguish between DNA and RNA, and more importantly, are capable of crossing multiple membrane barriers ranging from the cell/organelle to the tissue/organ level. We report the discovery of a cationic carbon quantum dot (cQD) probe that emits spectrally distinguishable fluorescence upon binding with double-stranded DNA and single-stranded RNA in live cells, thereby enabling real-time monitoring of DNA and RNA localization and motion. A surprising finding is that the probe can penetrate through various types of biological barriers in vitro and in vivo. Combined with standard and super-resolution microscopy, photostable cQDs allow time-lapse imaging of chromatin and nucleoli during cell division and Caenorhabditis elegans (C. elegans) growth.

Mitochondrial matrix contains numerous metabolism-related proteins/enzymes and nucleic acids, which play key roles in the process of energy generation and signal transduction. The fluctuations in mitochondrial biomacromolecular levels lead to the changes in the mitochondrial matrix viscosity; therefore, real-time measuring the mitochondrial matrix viscosity is of great significance for the in-depth understanding of the mitochondrial physiology and pathobiology. However, investigations are limited due to the lack of a mitochondrial matrix-specific molecular rotor. Herein, we report a design of a molecular rotor that is specifically enriched in the mitochondrial matrix. The red fluorescence of the rotor switches on when the viscosity increases, enabling the real-time monitoring of the viscosity change therein. Interestingly, the rotor showed non-fluorescence behaviour in the liposome (mimicking membrane structure), avoiding fluorescence interference from the mitochondrial bilayer membrane. Super-resolution imaging reveals that the viscosity is uneven in an individual mitochondrion.

Enzyme activity in live cells is dynamically regulated by small-molecule transmitters for maintaining normal physiological functions. A few probes have been devised to measure intracellular enzyme activities by fluorescent imaging, but the study of the regulation of enzyme activity via gasotransmitters in situ remains a long-standing challenge. Herein, we report a three-channel imaging correlation by a single dual-reactive fluorescent probe to measure the dependence of phosphatase activity on the H2S level in cells. The two sites of the probe reactive to H2S and phosphatase individually produce blue and green fluorescent responses, respectively, and resonance energy transfer can be triggered by their coexistence. Fluorescent analysis based on the three-channel imaging correlation shows that cells have an ideal level of H2S to promote phosphatase activity up to its maximum. Significantly, a slight deviation from this H2S level leads to a sharp decrease of phosphatase activity. The discovery further strengthens our understanding of the importance of H2S in cellular signaling and in various human diseases. Funding Agencies|National Basic Research Program of China [2015CB932002]; National Natural Science Foundation of China [21335006, 21475135, 21375131, 21775001, 21705001, 21602003]; Anhui Provincial Natural Science Foundation of China [1708085MC68, 1808085MB32]; Hefei Physical Science Center Foundation [2017FXZY001]

Hydrogen sulfide (H2S) is a key signaling molecule in the cytoprotection, vascular mediation and neurotransmission of living organisms. In-depth understanding of its production, trafficking, and transformation in cells is very important in the way H2S mediates cellular signal transductions and organism functions; it also motivates the development of H2S probes and imaging technologies. A fundamental challenge, however, is how to engineer probes with sensitivity and cellular penetrability that allow detection of spontaneous production of H2S in the entire cell space and live animals. Here, we report a rationally designed molecular switch capable of accessing all intracellular compartments, including the nucleus, lysosomes and mitochondria, for H2S detection. Our probe comprised three functional domains (H2S sensing, fluorescence, and biomembrane penetration), could enter almost all cell types readily, and exhibit a rapid and ultrasensitive response to H2S (≤120-fold fluorescence enhancement) for the dynamic mapping of spontaneously produced H2S as well as its distribution in the whole cell. In particular, the probe traversed blood/tissue/cell barriers to achieve mapping of endogenous H2S in metabolic organs of a live Danio rerio (zebrafish). These results open-up exciting opportunities to investigate H2S physiology and H2S-related diseases.

Understanding lysosome-related physiology needs specific lysosome probes to track the biological processes of lysosome in living cells. Here, we report an azacyclo-modified fluorescent probe that has a large Stokes shift, good photostability and negligible cytotoxicity for highly specific labeling of lysosome and autolysosome in living cells. The probes with different kinds of azacyclo groups on parent dye dansyl are screened to show that dansyl-cycleanine (DNS-C) with four nitrogen atoms possesses the best lysosome-localized ability. And DNS-C as a universal tracker exhibits excellent ability for lysosome labeling in different cell lines with high overlap coefficients (≥0.90). Different from a commercially available LysoTracker, the Stokes shift of DNS-C up to 240 nm (λex/em = 330/570 nm), is much larger than that of LysoTracker ~20 nm (λex/em = 573/595 nm). More importantly, the fluorescence of DNS-C keeps still high brightness after a time-lapsed imaging for 40 min in living cells, implying its remarkable photostability for long-term tracking. In addition, DNS-C can also clearly image the autolysosome, a critical subcellular compartment, forming by the fusion of lysosome with autophagosome in autophagy. These results suggest the promising utility of our probe as a powerful tool to real-time trace physiological processes of lysosomes.

Since the first discovery of luminescent graphene oxide (GO), exponentially increasing investigations on the tunable structures and surfaces for modulating its optical properties have struggled to expand applications in imaging, sensing, biomedical diagnostics, and so on. Here, the latest works on reconstructing or modifying the structures and surfaces of GO to achieve diverse luminescence are systematically reviewed, including fluorescence, electroluminescence, and chemiluminescence. Moreover, the fundamental difficulties of the investigations and applications of luminescent GO nanomaterials are clarified to inspire more constructive thoughts for expanding their application boundaries.

Investigating the interactions between lipid droplets (LDs) and other organelles are greatly significant to the in-depth understand the physiology and pathology of LDs. Despite of commercial LDs probes available, the ER and other membrane structures are also stained due to their amphiphilicity, which limits their further applications. To address this issue, we herein report a highly hydrophobic fluorescent probe to specifically label intracellular LDs with high signal/noise ratio, avoiding undesirable staining of ER and thus achieving to real-time monitor the interactions between LDs and other organelles. The probe showed strong emission in lipid environments but no fluorescence in water and liposomes, enabling the probe with high signal/noise ratio. Using this probe, it was found that the contacts of LDs with ER and mitochondria clearly increased under the condition of starvation.

High lipid metabolism is one of the fundamental characteristics of cancer cells different from normal cells due to lots of energy needed for the fast proliferation of cancer cells. As an important organelle to supply cellular energy, however, the difference of lipid droplets (LDs) in their dynamic features between cancer cells and normal cells remains unclear. A key difficulty is to develop a specific fluorescence-tunable probe with high signal-to-noise for rapidly and accurately identifying cancer cells via tracking lipid droplets’ dynamics. Here, we report a solvatochromic fluorescent probe, dansyl-morpholine (DNS-M), with high LDs-specificity to achieve the effective discrimination of cancer cells from normal cells by visually profiling the feature difference of LDs dynamics. Probe DNS-M is synthesized easily by one-step reaction, and possesses a large Stokes shift ∼200 nm, excellent photostablity and LDs-targeted capability with high overlap coefficient up to 0.97. Due to the remarkable biomembrance penetration, LDs-specificity and photostability, DNS-M has been applied to distinguish cancer cells from normal cells rapidly within 1 min in living cells and fixed cells, and real-time track dynamic behaviors of LDs in cancer cells, such as association, dissociation and fusion. More importantly, a significant difference in LDs behavior modes between cancer cells and normal cells is successfully visualized for the first time with our probe. We envision that our probe will become a rapid and easy-to-operate tool for cancer diagnosis and deeper understanding of LDs-related behaviors in cancer cells.

The structural features that render gold nanoclusters intrinsically fluorescent are currently not well understood. To address this issue, highly fluorescent gold nanoclusters have to be synthesized, and their structures must be determined. We herein report the synthesis of three fluorescent Au24 (SR)20 nanoclusters (R=C2 H4 Ph, CH2 Ph, or CH2 C6 H4 (t) Bu). According to UV/Vis/NIR, differential pulse voltammetry (DPV), and X-ray absorption fine structure (XAFS) analysis, these three nanoclusters adopt similar structures that feature a bi-tetrahedral Au8 kernel protected by four tetrameric Au4 (SR)5 motifs. At least two structural features are responsible for the unusual fluorescence of the Au24 (SR)20 nanoclusters: Two pairs of interlocked Au4 (SR)5 staples reduce the vibration loss, and the interactions between the kernel and the thiolate motifs enhance electron transfer from the ligand to the kernel moiety through the Au-S bonds, thereby enhancing the fluorescence. This work provides some clarification of the structure-fluorescence relationship of such clusters.

Investigating lipid droplets (LDs) behaviours is essential to deeply understand the physiology of LDs, such as their growths, movements, fusion/division, and autophagy. Among these behaviours, the growth of LDs is one of the most difficult to track due to the very subtle morphology evolution in a short time window. The major obstacle is that conventional LDs-specific dyes with low photostability cannot indicate the LDs’ size change. To address this issue, we synthesize a hydrophobic and photostable fluorescent dye (TPA-AD) and load it into the neutral lipid micelles (as artificial adiposomes). The highly hydrophobic TPA-AD enables the specific accumulation into intracellular LDs and the ready loading artificial adiposomes. When the intracellular LDs take TPA-AD-labeled adiposomes, by fusion, the sizes of LDs gradually grow, and LDs are simultaneously lighted up by the fluorescence of TPA-AD. Importantly, the high photostability of TPA-AD ensures the enhanced fluorescence signals. The finding here will further strengthen the understanding of LDs dynamics and fat metabolism.

Human telomerase RNA (hTR), a template of telomerase for telomeric repeat synthesis, was used to reflect the telomerase activity and act as a potential target of antitumor therapy. Here, we report a novel DNA-conjugated AuNP probe termed sticky-flares for the in situ detection of intracellular human telomerase RNA. The sticky-flares probe is capable of entering living cells directly without any auxiliary and recognizing the binding domain of human telomerase RNA. On recognition, the fluorophore-modified recognition flares can specifically bind to the target, separate from the sticky-flares and act as a fluorescent reporter to quantify and dynamically profile human telomerase RNA in living cells. We envision that the sticky-flares probe would be a valuable platform to investigate the function and regulation of hTR in antitumor therapy and hTR-related drug invention.

Distinguishing tumor cells from normal cells holds the key to precision diagnosis and effective intervention of cancers. The fundamental difficulties, however, are the heterogeneity of tumor cells and the lack of truly specific and ideally universal cancer biomarkers. Here, we report a concept of tumor cell detection, bypassing the specific genotypic and phenotypic features of different tumor cell types and directly going toward the hallmark of cancer, uncontrollable growth. Combining spherical nucleic acids (SNAs) with exquisitely engineered molecular beacons (SNA beacons, dubbed SNAB technology) is capable of identifying tumor cells from normal cells based on the molecular phenotype of telomerase activity, largely bypassing the heterogeneity problem of cancers. Owing to the cell-entry capability of SNAs, the SNAB probe readily achieves tumor cell detection across multiple platforms, ranging from solution-based assay, to single cell imaging and in vivo solid tumor imaging (unlike PCR that is restricted to cell lysates). We envision the SNAB technology will impact cancer diagnosis, therapeutic response assessment, and image-guided surgery.

Hydrogen sulfide (H2S) is a key signaling molecule in the cytoprotection, vascular mediation and neurotransmission of living organisms. In-depth understanding of its production, trafficking, and transformation in cells is very important in the way H2S mediates cellular signal transductions and organism functions; it also motivates the development of H2S probes and imaging technologies. A fundamental challenge, however, is how to engineer probes with sensitivity and cellular penetrability that allow detection of spontaneous production of H2S in the entire cell space and live animals. Here, we report a rationally designed molecular switch capable of accessing all intracellular compartments, including the nucleus, lysosomes and mitochondria, for H2S detection. Our probe comprised three functional domains (H2S sensing, fluorescence, and biomembrane penetration), could enter almost all cell types readily, and exhibit a rapid and ultrasensitive response to H2S (≤120-fold fluorescence enhancement) for the dynamic mapping of spontaneously produced H2S as well as its distribution in the whole cell. In particular, the probe traversed blood/tissue/cell barriers to achieve mapping of endogenous H2S in metabolic organs of a live Danio rerio (zebrafish). These results open-up exciting opportunities to investigate H2S physiology and H2S-related diseases.

Luminescent chemosensors for hydrogen sulphide (H2S) are of great interest because of the close association of H2S with our health. However, current probes for H2S detection have problems such as low sensitivity/selectivity, poor aqueous-solubility or interference from background fluorescence. This study reports an ultrasensitive and time-gated "switch on" probe for detection of H2S, and its application in test paper for visualization of exhaled H2S. The complex probe is synthesized with a luminescent Tb(3+) centre and three ligands of azido (-N3) substituted pyridine-2,6-dicarboxylic acid, giving the probe high hydrophilicity and relatively fast reaction dynamics with H2S because there are three -N3 groups in each molecule. The introduced -N3 group as a strong electron-withdrawing moiety effectively changes the energy level of ligand via intramolecular charge transfer (ICT), and thus breaks the energy transferring from ligand to lanthanide ion, resulting in quenching of Tb(3+) luminescence. On addition of H2S, the -N3 group can be reduced to an amine group to break the process of ICT, and the luminescence of Tb(3+) is recovered at a nanomolar sensitivity level. With a long lifetime of luminescence of Tb(3+) centre (1.9 ms), use of a time-gated technique effectively eliminates the background fluorescence by delaying fluorescence collection for 0.1 ms. The test paper imprinted by the complex probe ink can visualize clearly the trace H2S gas exhaled by mice.

Chemical sensing for the convenient detection of cancer cells has been widely explored with the use of various sensing materials and techniques, but it is still a challenge to achieve ultrasensitive, simple, rapid and inexpensive detection of cancer cells. Herein, we report a surface-enhanced Raman scattering (SERS) method for the detection of cancer cells in situ. In our work, ultrathin g-C3N4 nanosheet/Au@AgNP hybrids (g-C3N4/Au@AgNPs) were fabricated using a self-assembly strategy, in which poly(ethyleneimine) (PEI) was used to obtain cationic polyelectrolyte-modified ultrathin nanosheets and anchor the Au@AgNPs. The g-C3N4 nanosheets exhibited a strong enrichment ability and the self-assembled Au@AgNPs showed an excellent SERS activity, both of which led to an ultrahigh sensitivity. The hybrids were applied to detect folic acid (FA) with the sensitive detection limit of 2.41 nM. Importantly, after being modified with FA, which targeted cancer cells with folate receptors (FRs), the formed g-C3N4/Au@AgNPs–FA was used as a SERS probe for the on-site monitoring of cancer cells with FA as the Raman reporter molecule.

Precise identification and detection of cancer cells using nanoparticle probes are critically important for early cancer diagnosis and subsequent therapy. We herein develop novel folate receptor (FR)-targeted surface-enhanced Raman scattering (SERS) nanoprobes for cancer cell imaging based on a click coupling strategy. A Raman-active derivative (5,5′-dithiobis(2-nitrobenzoic acid)-N3 (DNBA-N3)) is designed with a disulfide bond for covalently anchoring to the surface of hollow gold nanoparticles (HAuNPs) and a terminal azide group for facilitating highly efficient conjugation with the bioligand. Modification of HAuNPs with DNBA-N3 yields monolayer coverage of Raman labels absorbed on the nanoparticle surface (HAuNP–DNBA-N3) and strong SERS signals. HAuNP–DNBA-N3 can be simply and effectively conjugated with folate bicyclo[6.1.0]nonyne derivatives via a copper-free click reaction. The synthesized nanoprobes (HAuNP–DNBA–folic acid (FA)) exhibit excellent targeted capacities to FR-positive cancer cells relat...

An electronic nose can detect highly volatile chemicals in foods, drugs, and environments, but it is still very much a challenge to detect the odors from crystalline compounds (e.g., solid explosives) with a low vapor pressure using the present chemosensing techniques in such way as a dog's olfactory system can do. Here, we inkjet printed silver nanoparticles (AgNPs) on cellulose paper and established a Raman spectroscopic approach to detect the odors of explosive trinitrotoluene (TNT) crystals and residues in the open environment. The layer-by-layer printed AgNP paper was modified with p-aminobenzenethiol (PABT) for efficiently collecting airborne TNT via a charge-transfer reaction and for greatly enhancing the Raman scattering of PABT by multiple spectral resonances. Thus, a Raman switch concept by the Raman readout of PABT for the detection of TNT was proposed. The AgNPs paper at different sites exhibited a highly uniform sensitivity to TNT due to the layer-by-layer printing, and the sensitive limit could reach 1.6 × 10(-17) g/cm(2) TNT. Experimentally, upon applying a beam of near-infrared low-energy laser to slightly heat (but not destruct) TNT crystals, the resulting airborne TNT in the open environment was probed at the height of 5 cm, in which the concentration of airborne species was lower than 10 ppt by a theoretical analysis. Similarly, the odors from 1.4 ppm TNT in soil and 7.2, 2.9, and 5.7 ng/cm(2) TNT on clothing, leather, and envelope, respectively, were also quickly sensed for 2 s without destoying these inspected objects.

Fluorescent probes are powerful tools for the investigations of reactive oxygen species (ROS) in living organisms by visualization and imaging. However, the multiparallel assays of several ROS with multiple probes are often limited by the available number of spectrally nonoverlapping chromophores together with large invasive effects and discrepant biological locations. Meanwhile, the spontaneous ROS profilings in various living organs/tissues are also limited by the penetration capability of probes across different biological barriers and the stability in reactive in vivo environments. Here, we report a single fluorescent probe to achieve the effective discrimination and profiling of hydroxyl radicals (•OH) and hypochlorous acid (HClO) in living organisms. The probe is constructed by chemically grafting an additional five-membered heterocyclic ring and a lateral triethylene glycol chain to a fluorescein mother, which does not only turn off the fluorescence of fluorescein, but also create the dual reactive sites to ROS and the penetration capability in passing through various biological barriers. The reactions of probe with •OH and HClO simultaneously result in cyan and green emissions, respectively, providing the real-time discrimination and quantitative analysis of the two ROS in cellular mitochondria. Surprisingly, the accumulation of probes in the intestine and liver of a normal-state zebrafish and the transfer pathway from intestine-to-blood-to-organ/tissue-to-kidney-to-excretion clearly present the profiling of spontaneous •OH and HClO in these metabolic organs. In particular, the stress generation of •OH at the fresh wound of zebrafish is successfully visualized for the first time, in spite of its extremely short lifetime.

The molecular processes of drugs from cellular uptake to intracellular distribution as well as the intracellular interaction with the target molecule are critically important for the development of new antitumor drugs. In this work, we have successfully developed a label-free surface-enhanced Raman scattering (SERS) technique to monitor and visualize the metabolism of antitumor drug 6-mercaptopurine in living cells. It has been clearly demonstrated that Au@Ag NPs exhibit an excellent Raman enhancement effect to both 6-mercaptopurine and its metabolic product 6-mercaptopurine-ribose. Their different ways to absorb at the surface of Au@Ag NPs lead to the obvious spectral difference for distinguishing the antitumor drug and its metabolite by SERS spectra. The Au@Ag NPs can easily pass through cell membranes in a large amount and sensitively respond to the biological conversion of 6-mercaptopurine in tumor cells. The Raman imaging can visualize the real-time distribution of 6-mercaptopurine and its biotransformation with the concentrations in tumor cells. The SERS-based method reported here is simple and efficient for the assessments of drug efficacy and the understanding of the molecular therapeutic mechanism of antitumor drugs at the cellular level.

Here, we report the shell thickness-dependent Raman enhancement of silver-coated gold nanoparticles (Au@Ag NPs) for the identification and detection of pesticide residues at various fruit peels. The Raman enhancement of Au@Ag NPs to a large family of sulfur-containing pesticides is ~2 orders of magnitude stronger than those of bare Au and Ag NPs, and there is a strong dependence of the Raman enhancement on the Ag shell thickness. It has been shown for the first time that the huge Raman enhancement is contributed by individual Au@Ag NPs rather than aggregated Au@Ag NPs with "hot spots" among the neighboring NPs. Therefore, the Au@Ag NPs with excellent individual-particle enhancement can be exploited as stand-alone-particle Raman amplifiers for the surface identification and detection of pesticide residues at various peels of fruits, such as apple, grape, mango, pear, and peach. By casting the particle sensors onto fruit peels, several types of pesticide residues (e.g., thiocarbamate and organophosphorous compounds) have been reliably/rapidly detected, for example, 1.5 nanograms of thiram per square centimeter at apple peel under the current unoptimized condition. The surface-lifting spectroscopic technique offers great practical potentials for the on-site assessment and identification of pesticide residues in agricultural products.

Correction for ‘Synthesis of g-C3N4 nanosheet/Au@Ag nanoparticle hybrids as SERS probes for cancer cell diagnostics’ by Jianping Wang et al., RSC Adv., 2015, 5, 86803–86810.

A chemically reactive Raman probe has been developed for ultrasensitively monitoring and imaging the in vivo generation of femtomolar oxidative species as induced by anti-tumor drugs in living cells.

Hydrophobic silver (Ag) nanoparticles of ∼16 nm diameter were self-assembled as building blocks in an emulsion to form large spherical clusters upon the removal of organic solvents. The self-assembled clusters of Ag nanoparticles have diameters in the range 0.5–1.0 μm and are composed of thousands of densely packed Ag nanoparticles, leading to the generation of multiple active sites or hot spots for surface-enhanced Raman scattering (SERS) in a single cluster, as clearly observed using confocal Raman microscopy. Such single clusters of Ag nanoparticles show significant SERS activity for Rhodamine-6G and dithiocarbamates such as thiram. The enhancement factor for R6G was calculated to reach 1 × 109, which is possible for the observation of SERS signals of a single molecule of R6G according to literature reports. The as-prepared individual clusters of Ag nanoparticles have been demonstrated for the SERS detection of the agricultural chemical thiram. The results show that the detection limit for thiram is as low as 0.024 ppm, which is much lower than the maximal residue limit (MRL) of 7 ppm in fruit prescribed by U.S. Environmental Protection Agency (EPA). The system also possesses the ability to selectively detect dithiocarbamate compounds over other types of agricultural chemical. Furthermore, spiked and recovery tests show that the Ag nanoparticle clusters can be used to detect thiram in natural lake water and commercial apple juice without much interference.