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Protein kinases constitute a rich pool of biomarkers and therapeutic targets of tremendous diseases including cancer. However, sensing kinase activity in vivo while implementing treatments according to kinase hyperactivation remains challenging. Herein, we present a nanomediator-effector cascade system that can in situ magnify the subtle events of kinase-catalyzed phosphorylation via DNA amplification machinery to achieve kinase activity imaging and kinase-responsive drug release in vivo. In this cascade, the phosphorylation-mediated disassembly of DNA/peptide complex on the nanomediators initiated the detachment of fluorescent hairpin DNAs from the nanoeffectors via hybridization chain reaction (HCR), leading to fluorescence recovery and therapeutic cargo release. We demonstrated that this nanosystem simultaneously enabled trace protein kinase A (PKA) activity imaging and on-demand drug delivery for inhibition of tumor cell growth both in vitro and in vivo, affording a kinase-specific sense-and-treat paradigm for cancer theranostics.

Dynamically monitoring intracellular glutathione (GSH), a crucial biomarker of oxidative stress, is of significance for the diagnosis and treatment of certain diseases. Although manganese dioxide (MnO2) based GSH fluorescent sensors have exhibited high sensitivity and good selectivity owing to the specific reactivity between GSH and MnO2, near-infrared (NIR) MnO2 based nanoprobes for GSH detection are scarce. Herein, we have developed a NIR activatable fluorescence nanoprobe for the imaging and determination of intracellular GSH based on a core-shell nanoparticle, consisting of NIR emitted gold nanocluster doped silica as the fluorescent core and manganese dioxide as the GSH-responsive shell (named AuNCs@MnO2). Due to the absorption competition mechanism, the outer MnO2 shell rather than the inner AuNCs core preferentially absorbed the excitation light, thus leading to fluorescence quenching of the inner AuNCs core. Upon addition of GSH, the fluorescence of the nanoprobe restored along with the reduction of MnO2 to Mn2+ because of the absorption competition disappearance-induced emission. The activatable fluorescence linearly increased upon changing the GSH concentration in the range of 2 to 5000 μM with a detection limit of 0.67 μM. The cytotoxicity test shows that the AuNCs@MnO2 nanoprobes have a good biocompatibility. After entering the cancer cells, the intracellular GSH degraded the outermost MnO2 shell and initiated the NIR fluorescence restoration of AuNCs, which can be used to monitor the dynamic change of intracellular GSH. This strategy provides an NIR-activatable way to detect GSH levels in living cells and offers a promising platform for the diagnosis and treatment of GSH-related diseases.

In recent years, Au and Ag nanomaterials have been widely used in the determination of glucose owing to their specific properties such as large specific surface area, high extinction coefficient, strong localized surface plasmon resonance effect and enzyme-mimicking activity. Compared with other methods, colorimetric determination of glucose with Au or Ag nanomaterials features the advantages of simple operation, low cost and easy observation. In this review, several typical synthesis methods of Au and Ag nanomaterials are introduced. Strategies for the colorimetric determination of glucose by Au or Ag nanomaterials are elaborated. The challenges and prospects of the application of Au or Ag nanomaterials for colorimetric detection of glucose are also discussed.

Great efforts have been devoted to the synthesis of various CsPbX3 nanostructures in view of their excellent photovoltaic performance and promising optoelectronic applications. However, the preparation of high-quality one-dimensional cesium lead halide nanotubes still remains challenging and unexplored. Here, we report a microwave-assisted synthetic approach for high-quality single crystalline CsPbI3 nanotubes featuring highly uniform sizes and stable and bright photoluminescence. Furthermore, a CsPbI3 nanotube based photodetector was assembled, which exhibits high sensitivity, stability and a fast response to 405 nm wavelength light. As a new member of the all-inorganic CsPbX3 nanostructure family, CsPbI3 nanotubes could provide a potential platform for understanding their fundamental properties and paving the way for their future application in optoelectronic devices.

In vivo monitoring of cargo protein delivery is critical for understanding the pharmacological efficacies and mechanisms during cancer therapy, but it still remains a formidable challenge because of the difficulty in observing nonfluorescent proteins at high resolution and sensitivity. Here we report an outer-frame-degradable nanovehicle featuring near-infrared (NIR) dual luminescence for real-time tracking of protein delivery in vivo. Upconversion nanoparticles (UCNPs) and fluorophore-doped degradable macroporous silica (DS) with spectral overlap were coupled to form a core-shell nanostructure as a therapeutic protein nanocarrier, which was eventually enveloped with a hyaluronic acid (HA) shell to prevent protein leakage and for recognizing tumor sites. The DS layer served as both a container to accommodate the therapeutic proteins and a filter to attenuate upconversion luminescence (UCL) of the inner UCNPs. After the nanovehicles selectively accumulated at tumor sites and entered cancer cells, intracellular hyaluronidase (HAase) digested the outermost HA protective shell and initiated the outer frame degradation-induced protein release and UCL restoration of UCNPs in the intracellular environment. Significantly, the biodistribution of the nanovehicles can be traced at the 710 nm NIR fluorescence channel of DS, whereas the protein release can be monitored at the 660 nm NIR fluorescence channel of UCNPs. Real-time tracking of protein delivery and release was achieved in vitro and in vivo by NIR fluorescence imaging. Moreover, in vitro and in vivo studies manifest that the protein cytochrome c-loaded nanovehicles exhibited excellent cancer therapeutic efficacy. This nanoplatform assembled by the outer-frame-degradable nanovehicles featuring NIR dual luminescence not only advances our understanding of where, when, and how therapeutic proteins take effect in vivo but also provides a universal route for visualizing the translocation of other bioactive macromolecules in cancer treatment and intervention.

Dynamically monitoring intracellular glutathione (GSH), a crucial biomarker of oxidative stress, is of significance for the diagnosis and treatment of certain diseases. Although manganese dioxide (MnO2) based GSH fluorescent sensors have exhibited high sensitivity and good selectivity owing to the specific reactivity between GSH and MnO2, near-infrared (NIR) MnO2 based nanoprobes for GSH detection are scarce. Herein, we have developed a NIR activatable fluorescence nanoprobe for the imaging and determination of intracellular GSH based on a core-shell nanoparticle, consisting of NIR emitted gold nanocluster doped silica as the fluorescent core and manganese dioxide as the GSH-responsive shell (named AuNCs@MnO2). Due to the absorption competition mechanism, the outer MnO2 shell rather than the inner AuNCs core preferentially absorbed the excitation light, thus leading to fluorescence quenching of the inner AuNCs core. Upon addition of GSH, the fluorescence of the nanoprobe restored along with the reduction of MnO2 to Mn2+ because of the absorption competition disappearance-induced emission. The activatable fluorescence linearly increased upon changing the GSH concentration in the range of 2 to 5000 μM with a detection limit of 0.67 μM. The cytotoxicity test shows that the AuNCs@MnO2 nanoprobes have a good biocompatibility. After entering the cancer cells, the intracellular GSH degraded the outermost MnO2 shell and initiated the NIR fluorescence restoration of AuNCs, which can be used to monitor the dynamic change of intracellular GSH. This strategy provides an NIR-activatable way to detect GSH levels in living cells and offers a promising platform for the diagnosis and treatment of GSH-related diseases.

Monitoring drug release in vitro and in vivo is of paramount importance to accurately locate diseased tissues, avoid inappropriate drug dosage, and improve therapeutic efficiency. In this regard, it is promising to develop strategies for real-time monitoring of drug release inside targeted cells or even in living bodies. Thus far, many multi-functional drug delivery systems constructed by a variety of building blocks, such as organic molecules, polymeric nanoparticles, micelles, and inorganic nanoparticles, have been developed for drug release monitoring. Especially, with the advancements in imaging modalities relating to nanomaterials, there has been an increasing focus on the use of non-invasive imaging techniques for monitoring drug release and drug efficacy in recent years. In this review, we introduce the application of fluorescence imaging, magnetic resonance imaging (MRI), surface-enhanced Raman scattering (SERS), and multi-mode imaging in monitoring drug release, involving a variety of nanomaterials such as organic or inorganic nanoparticles as imaging agents; their design principles are also elaborated. Among these, a special emphasis is placed on fluorescence-based drug release monitoring strategies, followed by a brief overview of MRI, SERS, and multi-mode imaging-based strategies. In the end, the challenges and prospects of drug release monitoring are also discussed.

A highly sensitive triple-amplification assay for the detection of microRNA (miRNA) let-7a is reported in this work. The assay relies on the formation of magnetic two-dimensional DNA/Fe3O4 nanosheet networks initiated by the target miRNA-associated hybridization chain reaction. The Fe3O4 nanosheets in the DNA/Fe3O4 networks display peroxidase-like catalytic activity towards a colorimetric reaction, thereby producing a highly sensitive signal for the quantification of let-7a. Under optimal conditions, the assay achieved a detection limit of 13 aM at a signal-to-noise ratio of 3 and a linear calibration plot between 0.05 fM and 12 nM. Successful attempts were made in the quantification of let-7a in serum samples.

In this study, a novel flower-like Co-TCPP MOF/rGO composite has been successfully synthesized by combining cobalt meso-tetrakis(4-carboxyphenyl) porphyrin (Co-TCPP MOF) and reduced graphene oxide (rGO) via a simple one-pot solvothermal method. The introduction of rGO not only reduces the stacking of MOF effectively, but also facilitates the formation of a continuous conductive network composed of entangled graphene and Co-TCPP MOF in favor of rapid electron transport. More importantly, the ultrathin lamellar structure of Co-TCPP MOF/rGO composite nanosheets could expose more active sites, reduce the diffusion distance of Li+ to the internal electroactive sites, and improve the overall electrical conductivity of the electrode due to their sufficient contact with carbon. When evaluated as anode materials for lithium-ion batteries, the flower-like Co-TCPP MOF/(15 wt%)rGO composite electrode delivers a specific capacity of 1050 mAh g−1 at 100 mA g−1 after 100 cycles. A specific capacity of 650 mAh g−1 can be remained after 300 cycles even at 1000 mA g−1. The superior performance of the Co-TCPP MOF/(15 wt%)rGO composite electrode could be attributed to the introduction of rGO, which prevents the stacking growth of Co-TCPP MOF crystals along the horizontal direction and improves the electrical conductivity.

A precisely controlled drug release is a great challenge in exploring methodologies of drug administration and fighting drug resistance for successful cancer chemotherapy. Herein, we developed a dual-mode nanocarrier to specifically deliver doxorubicin (Dox) and precisely control the drug release in target tumor cells. This hierarchical nanocarrier consisted of a gold nanorod as the heating core, biodegradable mesoporous silica as the storage chamber, and graphene quantum dot (GQD) as a drug carrier. The Arg-Gly-Asp peptides on the nanocarrier surface facilitated the specific interaction with integrin-overexpressed tumor cells and subsequent uptake via receptor-mediated endocytosis. Once exposed under the near-infrared (NIR) laser, the internalized nanocarrier rapidly heated the surrounding environment, which led to an instantaneous drug release by collapsing the π-π interaction between Dox and GQDs at high temperature and thereby intensified therapeutic efficacy. On the other hand, the silica shells underwent gradual degradation in the cellular matrix environment, along with stepwise liberation of the embedded GQD-Dox composites from the confined porous structure for the Dox release, exerting a long-term lethality to the tumor cells. By virtue of the physicochemical properties and synergistic behavior of the multiple components in this hierarchical nanocarrier, the NIR-triggered prompt release mode and the biodegradation-mediated slow release mode functioned in a precise and collaborative fashion, providing a promising way to manipulate the pharmacokinetics for precise cancer treatment.

Halide perovskite materials have emerged as a new class of revolutionary photovoltaic and optoelectronic nanomaterials. However, the study on electrochemiluminescence (ECL) from halide perovskite nanomaterials is still in its infancy due to their instability, sensitivity, and difficulties in purification and film formation. Here, we propose a scraping coating method for the fabrication of high-quality halide perovskite quantum dot (QD) film on electrode, which shows dense and uniform packing with minimum grain size. When CsPbBr3 QDs are taken as model materials, highly efficient ECL can be obtained from such perovskite QD film with anhydrous ethyl acetate as both electrolyte and coreactant. The CsPbBr3 QD film displays intense and stable ECL with ultranarrow emission spectrum bandwidth (24 nm). The CsPbBr3 QD film shows an extremely high ECL efficiency which is up to 5 times relative to the standard Ru(bpy)32+/tri-n-propylamine system. This approach is universal and also applies to hybrid organic–inorgani...

A highly sensitive triple-amplification assay for the detection of microRNA (miRNA) let-7a is reported in this work. The assay relies on the formation of magnetic two-dimensional DNA/Fe

Great challenges in investigating the release of drug in complex cellular microenvironments necessitate the development of stimuli-responsive drug delivery systems with real-time monitoring capability. In this work, a smart drug nanocarrier based on fluorescence resonance energy transfer (FRET) is fabricated by capping graphene quantum dots (GQDs, the acceptor) onto fluorescent mesoporous silica nanoparticles (FMSNs, the donor) via ATP aptamer for real-time monitoring of ATP-triggered drug release. Under extracellular conditions, the fluorescence of FMSNs remains in the "off" state in the low ATP level which is unable to trigger the release of drug. Once specifically recognized and internalized into the target tumor cells by AS1411 aptamer, in the ATP-rich cytoplasm, the conformation switch of the ATP aptamer causes the shedding of the GQDs from the nanocarriers, leading to the release of the loaded drugs and consequently severe cytotoxicity. Simultaneously, the fluorescence of FMSNs turns "on" along with the dissociation of GQDs, which allows real-time monitoring of the release of drug from the pores. Such a drug delivery system features high specificity of dual-target recognition with AS1411 and ATP aptamer as well as high sensitivity of the FRET-based monitoring strategy. Thus, the proposed multifunctional ATP triggered FRET-nanocarriers will find potential applications for versatile drug-release monitoring, efficient drug transport, and targeted cancer therapeutics.

We present a simple and effective fluorescence method for the detection of 2,4,6-trinitrotoluene (TNT), which is based on TNT recognition by amine-capped silicon quantum dots (SiQDs). The highly luminescent functionalized SiQDs were obtained by a one-step hydrothermal process, using 3-aminopropyltrimethoxysilane as the precursor. The as-prepared SiQDs were directly used as a recognition probe for the detection of TNT because of the strong interactions between the TNT molecule and the SiQDs with an amine group. The formation of Meisenheimer complexes (TNT–amine complexes) could quench the fluorescence of SiQDs by fluorescence resonance energy transfer. Such fluorescence response could be used to quantify TNT over the range of 5–500 nM with a detection limit down to 1 nM, and has been successfully applied for the assay of TNT in spiked tap water. The probe exhibited excellent selectivity. This method has great potential for applications in TNT detection.

Stereoselective preparation of alkenyl sulfide was carried out via syn-hydrozirconation of the alkynyl sulfide. Regiochemistry of halogenation of the thioalkenyl zirconocene could be switched by different halides. α-Chloroalkenyl sulfide or β-haloalkenyl sulfide (Br, I) could be obtained by the treatment of NCS or NBS (NIS), respectively. Possible mechanism of halogenation of the thioalkenyl zirconocene was set up herein.

The appointment system in clinics is a service to facilitate the patients’ convenience. The problems existing in the practice of appointment registration, carried out by oral speciality hospitals, include: the intense disparity between supply and demand of oral medical centers, the long cycle of patient engagement; the high rate of appointments broken by outpatients, etc. In view of these problems, this paper proposes that medical organizations actively search for effective solutions, to boost the practice of clinical appointment registration, under the normal conditions of hospital operation and care environment, such as putting more efforts into the spot dissemination and guidance; buffering the disparity between supply and demand appropriately; arranging reasonable appointment cycles, and controlling the rate of appointment-breakage.

A one-pot synthesis of alkynyl sulfide from terminal alkyne has been reported via lithiation of the alkyne, oxidative addition of sulfur, consecutively followed by the nucleophilic substitution of lithium alkynyl thiolate to various halides. © 2011 Wiley Periodicals, Inc. Heteroatom Chem 23:105–110, 2012; View this article online at wileyonlinelibrary.com. DOI 10.1002/hc.20745

The polyaniline (PAN)-coated CdSeTe quantum dots (QDs) were prepared by in situ polymerization of aniline on the surface of CdSeTe QDs. The PAN-coated CdSeTe QDs has a tremendously enhanced fluorescence (∼40 times) and improved biocompatibility compared to the uncoated CdSeTe QDs. The fluorescence intensity of the PAN-coated CdSeTe QDs can be adjusted by controlling the construction parameters of the PAN shell. The kinetics of the in situ controllable polymerization process was studied by varying the temperature, and the apparent activation energy of polymerization was estimated. With the same method, a series of the PAN derivatives were also tested to coat the CdSeTe QDs in this study. All the QDs showed a significant enhancement of the fluorescence intensity and better biocompatibility. The significantly enhanced fluorescence can provide highly amplified signal for luminescence-based cell imaging.

Intracellular imaging of pathologically relevant proteases can provide essential information for the accurate evaluation of disease stage and progression. However, the risks of degradation by nonspecific enzymes during transportation and poor cellular uptake limit the use of peptide-based molecular probes (PMPs) for in situ protease imaging. To overcome these obstacles, a self-protected nanovehicle with a peptide-mediated core/satellite/shell structure was constructed for precise imaging of the protease cathepsin B (Cat B) in situ and the subsequent Cat B-responsive drug release. The self-protected nanovehicles demonstrated excellent resistance to nonspecific enzymolysis, thereby keeping the embedded PMPs intact until they reach the target organelle. Furthermore, the targeting ability of the outer shell facilitated the internalization of nanovehicles into tumor cells via receptor-guided recognition: the protective shell thereafter degraded in the intracellular microenvironment, and Cat B activity was dynamically monitored as the core/satellite structure disassembled. Meanwhile, the peptide-mediated satellite/shell structures served as three-dimensional gatekeepers to lock doxorubicin inside the nanovehicles, and drug release was spatiotemporally controlled by Cat B activity. This study provides important guiding principles for the rational design of self-protected nanovehicles for accurate diagnosis and therapy. A nanomaterial that glows only in the presence of cancer-related protease enzymes also delivers drugs to these cells. The approach from Jun-Jie Zhu and co-workers from Nanjing University uses peptides, modified with fluorescent components, to enter cells and emit light when triggered by protease cleavage. Such probes often show false signals due to degradation of unrelated enzymes; the Chinese team overcame this problem by using silica ‘nanovehicles’ filled with fluorescent dopants. After tethering peptides to the silica core, they switched fluorescence off using a gold nanocluster layer and coated the probe with a molecular coating that rejects enzymes other than the intended biomolecule. Live cell trials revealed the nanovehicles remained dark until digested by specific proteases, separating gold and silica components. Loading drugs into the hollow silica core also enabled targeted release during cleavage. A self-protected nanovehicle with peptide-mediated core/satellite/shell structure was constructed for precise imaging of protease cathepsin B (Cat B) in situ and subsequent Cat B-responsive drug release. The self-protected nanovehicles have demonstrated excellent resistant ability to nonspecific enzymolysis, thereby keeping the embedded peptide-based molecular probes with core/satellite structure intact until reaching the target organelle.

α-Methylenyl zirconacyclopentenes are synthesized regio- and stereoselectively via reductive intermolecular cross-coupling of alkynes and allenes promoted by zirconocene species ‘Cp2Zr’. An interesting reductive intramolecular coupling of the α-methylenyl zirconacyclopentene has been observed in the presence of DMAD/CuCl, resulting in the generation of cyclobutene with an exocyclic double bond. Polysubstituted 1,4-dienes can be given with high selectivity and good yields.

Readily and commercially available substances are used in the convenient, safe, and atom-economical synthesis of compounds (III) and (V).

Reductive intermolecular cross-coupling of alkynes with allenes, promoted by ZrEt2Cp2, gives the title zirconacycle.

Herein, we designed a peptide chain with a special sequence and constructed a novel label-free fluorescent turn-on biosensor for the assay of trypsin based on the interaction between the designed peptide and quantum dots. Using this sensor, trypsin can be detected sensitively with a detection limit of 20 ng mL−1, even by the naked eye under a UV lamp.