Ti3AlC2 MXene nanosheets as a novel corrosion inhibitor for carbon steel in 0.5 M sulfuric acid solution.

Herein we report that Ti3AlC2 MXene nanosheets were identified as a highly effective cathodic protection corrosion inhibitor for carbon steel in hydrochloric acid solution. Ti3AlC2 Mxene nanosheets form a stable inhibition layer on metal surfaces due to their high adsorption capacity and act as a barrier or protective film to prevent attacks from corrosive substances and thus lead to an extended metal service life.

Pt(II) metallacycles encapsulated by ferritin enable precise cancer combination chemo-photodynamic therapy.

Different from common anti-tumor drugs, organoplatinum(II) metallacycles can integrate imaging and other therapeutic capabilities by incorporating corresponding functional donor ligands to enable potential applications in biomedicine. However, most of the emerging therapeutic agents not only show poor solubility and selectivity but also have serious side effects and unsatisfactory efficacy and encounter the tendency to develop drug resistance due to their single treatment model. Herein, an organoplatinum(II) metallacycle (PtM) was designed and synthesized using coordination-driven self-assembly via the combination of a metallic chemotherapy precursor and a reactive oxygen species generating organic precursor. The hydrophobic PtM molecules were encapsulated in the cavity of human heavy chain ferritin (HFn) during the reassembly of HFn to prepare the active targeting nanoagent HFn-PtM for use in chemo-photodynamic combination therapy. The HFn-PtM nanoagents exhibited excellent stability in buffer (pH from 5 to 7.2), alleviating the concern of drug leakage during circulation. A cellular uptake assay indicated that HFn-PtM could efficiently enter specific cells that overexpress the transferrin receptor 1. In vitro and in vivo anti-tumor investigations revealed that HFn-PtM exhibited excellent anti-tumor efficiency with negligible systemic toxicity. This work provides a strategy for the easy construction of multifunctional organoplatinum-based tumor-targeted drugs.

Facile surface functionalization of MXene by pillar[5]arene for enhanced electrochemical performance.

A simple strategy was used to prepare functional two-dimensional materials via the combination of pillar[5]arene (P5) and MXene. The electrochemical results of MXene-P5 exhibit high supramolecular recognition, enrichment capability, and high electrochemical response toward dye molecules, which are probably due to the synergetic effects from high conductivity, high surface area, and host-guest recognition. This study provides a promising electrochemical sensing platform based on different kinds of pillararenes.

Inorganic-Organic Hybrid Membrane Based on Pillararene-Intercalated MXene Nanosheets for Efficient Water Purification.

Discharge of antibiotic-containing wastewater causes environmental pollution and threatens biological and human health. An efficient treatment method for this wastewater is urgently required. We prepared inorganic-organic hybrid MXene-pillararene nanosheets with a large lateral size (5-8 µm). The hybrid nanosheets were stacked on supports via vacuum-assisted filtration to prepare membranes with regular parallel slits and an interlayer spacing of 1.36 nm, which were used to purify antibiotic-containing water. Permeance through the membrane increased 100-fold compared with most polymeric and other two-dimensional nanofiltration membranes with similar rejection. This high permeance and rejection was attributed to the large lateral size of the nanosheets, regular interlayer spacing, and electrostatic interaction between the membrane and antibiotics. These membranes will broaden the applications of lamellar materials for the separation of high-value-added drugs in academia and industry.

Photoresponsive Solid Nanochannels Membranes: Design and Applications.

Light stimuli have notable advantages over other environmental stimuli, such as more precise spatial and temporal regulation, and the ability to serve as an energy source to power the system. In nature, photoresponsive nanochannels are important components of organisms, with examples including the rhodopsin channels in optic nerve cells and photoresponsive protein channels in the photosynthesis system of plants. Inspired by biological channels, scientists have constructed various photoresponsive, smart solid-state nanochannels membranes for a range of applications. In this review, the methods and applications of photosensitive nanochannels membranes are summarized. The authors believe that this review will inspire researchers to further develop multifunctional artificial nanochannels for applications in the fields of biosensors, stimuli-responsive smart devices, and nanofluidic devices, among others.

Encapsulation of NIR-II AIEgens in Virus-like Particles for Bioimaging.

The development of organic nanoparticles that fluoresce in the near-infrared, especially in the second near-infrared (NIR-II) window, improves in vivo fluorescence imaging due to deeper penetration and higher spatiotemporal resolution. We report two kinds of NIR-II fluorescent molecules with twisted intramolecular charge-transfer (TICT) and aggregation-induced emission (AIE) characteristics. The virus-like particles (VLPs) of simian virus 40 (SV40) were used as templates to encapsulate the molecules in a well-defined structure (referred to as CH1-SV40 and CH2-SV40). The CH1-SV40 dots exhibited a highly uniform size of 21.5 nm, strong fluorescence, high photostability, and good biocompatibility in vitro and in vivo. Their fluorescence spectrum exhibited a peak at 955 nm, with a tail extending to 1200 nm. Moreover, the CH1-SV40 dots, with a quantum yield of 13.03%, enabled blood vessel imaging and image-guided surgery with a high signal-to-background ratio. Overall, the hybrid nanoparticles represent a new kind of NIR-II AIE nanoprobes for biomedical imaging.

AIE nanodots scaffolded by mini-ferritin protein for cellular imaging and photodynamic therapy.

Photodynamic therapy (PDT) is one of the most elegant cancer treatment strategies that can be controlled by a beam of light with non-invasion, precise control, and high spatiotemporal accuracy. An ideal photosensitizer (PS) is the key to ensure the efficacy of PDT. Due to their hydrophobic and rigid planar structures, most traditional PSs are prone to aggregate under physiological conditions, which causes fluorescence quenching and significantly reduces reactive oxygen species (ROS) generation. Fortunately, the emergence of aggregation-induced emission (AIE) dyes offers a potential opportunity to overcome these limitations. When AIE PS molecules are in the aggregation state, the fluorescence intensity and ROS production can be increased. We herein use red AIE PS molecules to prepare stable AIE nanodots for cell imaging and PDT via a simple method with a highly negatively charged mini-ferritin protein as the scaffold. The as-prepared protein-AIE nanodots show strong fluorescence emission and efficient singlet oxygen generation, with good stability, relatively long wavelengths of absorption and emission, and negligible dark toxicity. The mini-ferritin-AIE system may be useful in developing novel functional probes for tumour nanotheranostics.

DNA-Conjugated Amphiphilic Aggregation-Induced Emission Probe for Cancer Tissue Imaging and Prognosis Analysis.

Detection of an ultralow concentration of mRNA is important in the prognosis of gene-related diseases. In this study, a DNA-conjugated amphiphilic aggregation-induced emission probe (TPE-R-DNA) was synthesized for cancer tissue imaging and prognosis analysis based on an exonuclease III-aided target recycling technique. TPE-R-DNA comprise two components: a hydrophobic component that serves as the "turn-on" long wavelength fluorescence imaging agent (TPE-R-N3); and a hydrophilic single DNA strand (Alk-DNA) which acts as specific recognition part for target mRNA. In the absence of target mRNA, TPE-R-DNA had almost no fluorescence because of its high water solubility. Conversely, the TPE-R-DNA was digested by exonuclease III (Exo III) in the presence of MnSOD mRNA to release the hydrophobic fluorogens (TPE-R-AT). Subsequently, TPE-R-AT formed aggregates, and therefore, fluorescence signal was distinctly observed. For the first time, the structure of the hydrolysis product (TPE-R-AT), containing two bases A and T, was proved by the mass spectrum (MS) and high-performance liquid chromatography (HPLC). Moreover, the detection limit toward mRNA could be achieved in as low as 0.6 pM. Furthermore, the fluorescent signal can be used to confirm the MnSOD mRNA expression level in cancer tissue. The MnSOD mRNA expression in renal cancer was lower than in renal cancer adjacent tissue. In particular, the expression level was analyzed to predict prognosis of cancer patients. Our results demonstrate that a shorter survival time was evident among patients in lower MnSOD mRNA expression. Thereby, it indicates great potential for the development of an ultrasensitive biosensing platform for the application in disease prognosis.

AIE-based superwettable microchips for evaporation and aggregation induced fluorescence enhancement biosensing.

Superwettable microchips with superhydrophilic microwells on superhydrophobic substrate have attracted increasing attention in fluorescence-based biological and medical diagnostics. However, traditional fluorophores often suffer from the aggregation-caused quenching (ACQ) problem at high concentration or in aggregated state. Here, we developed an AIE-based superwettable microchip by combining the evaporation-induced enrichment of superwettable microchips and the aggregation-induced emission of AIEgens together into one chip. Benefitting from the synergistic effect of the above two mechanisms, the AIE molecules (TPE-Z, a tetraphenylethene salt) were enriched from the diluted solution via evaporation and aggregated within the superhydrophilic microwell and then realized the fluorescence enhancement. Based on the dual enhancement effect of the AIE-based superwettable microchip, microRNA-141 (miR-141) can be detected with excellent reproducibility, sensitivity and specificity. A low detection limit of 1 pM can be achieved with higher signal-to-noise ratio than the traditional fluorescent probes. The proposed AIE-based superwettable microchip will provide a simple fluorescence enhancement biosensing platform for rapid, multiplexed and high-throughput analysis of specific targets in environmental monitoring, food safety, medical diagnosis and related research areas.

An AIEgens and exonuclease III aided quadratic amplification assay for detecting and cellular imaging of telomerase activity.

Monitoring telomerase activity with high sensitive and reliable is of great importance to cancer analysis. In this paper, we report a sensitive and facile method to detect telomerase activity using AIEgens modified probe (TPE-Py-DNA) as a fluorescence reporter and exonuclease III (Exo III) as a signal amplifier. With the aid of telomerase, repeat units (TTAGGG)n are extended from the end of template substrate oligonucleotides (TS primer) that form duplex DNAs with TPE-Py-DNA. Then, Exo III catalyzes the digestion of duplex DNAs, liberating elongation product and releasing hydrophobic TPE-Py. The released hydrophobic TPE-Py aggregate together and produce a telomerase-activity-related fluorescence signal. The liberated product hybridizes with another TPE-Py-DNA probe, starting the second cycle. Finally, we obtain the target-to-signal amplification ratio of 1:N2. This strategy exhibits good performance for detecting clinical urine samples (distinguishing 15 cancer patients' samples from 8 healthy ones) and checking intracellular telomerase activity (differentiating cell lines including HeLa, MDA-MB-231, MCF-7, A375, HLF and MRC-5 from the cells pretreated with telomerase-related drug), which shows its potential in clinical diagnosis as well as therapeutic monitoring of cancer.

Protease-Responsive Prodrug with Aggregation-Induced Emission Probe for Controlled Drug Delivery and Drug Release Tracking in Living Cells.

Controlled drug delivery and real-time tracking of drug release in cancer cells are essential for cancer therapy. Herein, we report a protease-responsive prodrug (DOX-FCPPs-PyTPE, DFP) with aggregation-induced emission (AIE) characteristics for controlled drug delivery and precise tracking of drug release in living cells. DFP consists of three components: AIE-active tetraphenylethene (TPE) derivative PyTPE, functionalized cell penetrating peptides (FCPPs) containing a cell penetrating peptide (CPP) and a short protease-responsive peptide (LGLAG) that can be selectively cleaved by a cancer-related enzyme matrix metalloproteinase-2 (MMP-2), and a therapeutic unit (doxorubicin, DOX). Without MMP-2, this prodrug cannot go inside the cells easily. In the presence of MMP-2, DFP can be cleaved into two parts. One is cell penetrating peptides (CPPs) linked DOX, which can easily interact with cell membrane and then go inside the cell with the help of CPPs. Another is the PyTPE modified peptide which will self-aggregate because of the hydrophobic interaction and turn on the yellow fluorescence of PyTPE. The appearance of the yellow fluorescence indicates the release of the therapeutic unit to the cells. The selective delivery of the drug to the MMP-2 positive cells was also confirmed by using the intrinsic red fluorescence of DOX. Our result suggests a new and promising method for controlled drug delivery and real-time tracking of drug release in MMP-2 overexpression cells.

Live Cell MicroRNA Imaging Using Exonuclease III-Aided Recycling Amplification Based on Aggregation-Induced Emission Luminogens.

Enzyme-assisted detection strategies of microRNAs (miRNAs) in vitro have accomplished both great sensitivity and specificity. However, low expression of miRNAs and a complex environment in cells induces big challenges for monitoring and tracking miRNAs in vivo. The work reports the attempt to carry miRNA imaging into live cells, by enzyme-aided recycling amplification. We utilize facile probes based yellow aggregation-induced emission luminogens (AIEgens) with super photostable property but without quencher, which are applied to monitor miRNAs not only from urine sample extracts (in vitro) but also in live cells (in vivo). The assay could distinguish the cancer patients' urine samples from the healthy urine due to the good specificity. Moreover, the probe showed much higher fluorescence intensity in breast cancer cells (MCF-7) (miR-21 in high expression) than that in cervical cancer cells (HeLa) and human lung fibroblast cells (HLF) (miR-21 in low expression) in more than 60 min, which showed the good performance and super photostability for the probe in vivo. As controls, another two probes with FAM/Cy3 and corresponding quenchers, respectively, could perform miRNAs detections in vitro and parts of in vivo tests but were not suitable for the long-term cell tracking due to the photobleach phenomena, which also demonstrates that the probe with AIEgens is a potential candidate for the accurate identification of cancer biomarkers.

A photostable AIE fluorogen for lysosome-targetable imaging of living cells.

Disruptive variation in intracellular pH and its fluctuations in lysosomes have a close relationship with the more acidic lysosome lumen of cancer cells (pH 4.5-5.5). Traditional lysosome-targeted probes, such as LysoTracker Green DND-26 (LTG) and LysoTracker Red DND-99 (LTR), can fluoresce when the weak base units in the probes are removed after donating protons under the photoinduced electron-transfer (PET) effect. However they can only be used at low concentration to avoid the aggregation-caused quenching (ACQ) effect and are also easily photobleached under continuous excitation irradiation, displaying low photostability. Herein, a tetraphenylethylene (TPE)-based lysosome-targetable fluorescence probe, TPE-CA, was synthesized, which could selectively monitor the pH change in subcellular organelles and exhibited a strong blue emission under an acidic condition with pH = 4. Using crystallographic, NMR and HRMS analyses, the mechanism regarding the pH dependent fluorescent performance of TPE-CA has been illustrated at the molecular level. In addition, experimental results show that TPE-CA is cell-permeable and biocompatible with HeLa, MCF-7 and HLF cells. The punctate fluorescent spots in the co-staining experiment of TPE-CA with LTG and LTR proves that the blue fluorescence spots of TPE-CA are indeed localized in the most acidic lysosome organelles. In particular, TPE-CA also inherits the aggregation-induced emission (AIE) feature of TPE, showing better photostability under continuous UV illumination compared with the commercial dyes (LTG and LTR). These results show that TPE-CA would be beneficial for understanding the acid environment of lysosomes in related cells and organs with potential biological significance.

Correction: A photostable AIE fluorogen for lysosome-targetable imaging of living cells.

Correction for 'A photostable AIE fluorogen for lysosome-targetable imaging of living cells' by Xiaoding Lou et al., J. Mater. Chem. B, 2016, 4, 5412-5417.

Quencher group induced high specificity detection of telomerase in clear and bloody urines by AIEgens.

Telomerase is a widely used tumor biomarker for early cancer diagnosis. On the basis of the combined use of aggregation-induced emission (AIE) fluorogens and quencher, a quencher group induced high specificity strategy for detection of telomerase activity from cell extracts and cancer patients' urine specimens was creatively developed. In the absence of telomerase, fluorescence background is extremely low due to the short distance between quencher and AIE dye. In the addition of telomerase, fluorescence enhances significantly. The telomerase activity in the E-J, MCF-7, and HeLa extracts equivalent to 5-10 000 cells can be detected by this method in ∼1 h. Furthermore, the distinguishing of telomerase extracted from 38 cancer and 15 normal urine specimens confirms the reliability and practicality of this protocol. In contrast to our previous results (Anal. Chem. 2015, 87, 6822-6827), these advanced experiments obtain more remarkable specificity.

Lab in a Tube: Sensitive Detection of MicroRNAs in Urine Samples from Bladder Cancer Patients Using a Single-Label DNA Probe with AIEgens.

We demonstrate an ultrasensitive microRNA detection method based on an extremely simple probe with only fluorogens but without quencher groups. It avoids complex and difficult steps to accurately design the relative distance between the fluorogens and quencher groups in the probes. Furthermore, the assay could accomplish various detection limits by tuning the reaction temperature due to the different activity of exonuclease III corresponding to the diverse temperature. Specifically, 1 pM miR-21 can be detected in 40 min at 37 °C, and 10 aM (about 300 molecules in 50 µL) miR-21 could be discriminated in 7 days at 4 °C. The great specificity of the assay guarantees that the real 21 urine samples from the bladder cancer patients are successfully detected by our method.

Real-Time, Quantitative Lighting-up Detection of Telomerase in Urines of Bladder Cancer Patients by AIEgens.

As a biomarker for early cancer diagnosis, telomerase are one of the promising targets for cancer therapeutics. Inspired by the fluorescent emission principle of aggregation-induced emission fluorogens, we creatively designed an AIE-based turn-on method to detect telomerase activity from cell extracts. A positively charged fluorogen (TPE-Z) is not fluorescent when freely diffused in solution. The fluorescence of TPE-Z is enhanced with the elongation of the DNA strand which could light up telomere elongation process. By exploitation of it, we can detect telomerase activity from different cell lines (E-J, HeLa, MCF-7, and HLF) with high sensitivity and specificity. Moreover, our method is successfully employed to demonstrate the applications in bladder cancer diagnosis (41 urine specimens from bladder cancer patients and 15 urine specimens from normal people are detected). The AIE-based method provides a simple one-pot technique for quantification and monitoring of the telomerase activity and shows great potential for future use in clinical tests.

Biocompatible Green and Red Fluorescent Organic Dots with Remarkably Large Two-Photon Action Cross Sections for Targeted Cellular Imaging and Real-Time Intravital Blood Vascular Visualization.

Fluorescent organic dots are emerging as promising bioimaging reagents because of their high brightness, good photostability, excellent biocompatibility, and facile surface functionalization. Organic dots with large two-photon absorption (TPA) cross sections are highly desired for two-photon fluorescence microscopy. In this work, we report two biocompatible and photostable organic dots fabricated by encapsulating tetraphenylethene derivatives within DSPE-PEG matrix. The two organic dots show absorption maxima at 425 and 483 nm and emit green and red fluorescence at 560 and 645 nm, with high fluorescence quantum yields of 64% and 22%, respectively. Both organic dots exhibit excellent TPA property in the range of 800-960 nm, affording upon excitation at 820 nm remarkably large TPA cross sections of 1.2×10(6) and 2.5×10(6) GM on the basis of dot concentration. The bare fluorophores and their organic dots are biocompatible and have been used to stain living cells for one- and two-photon fluorescence bioimagings. The cRGD-modified organic dots can selectively target integrin αvß3 overexpressing breast cancer cells for targeted imaging. The organic dots are also applied for real-time two-photon fluorescence in vivo visualization of the blood vasculature of mouse ear, providing the spatiotemporal information about the whole blood vascular network. These results demonstrate that the present fluorescent organic dots are promising candidates for living cell and tissue imaging.