Enhanced Antibacterial Activity against Escherichia coli Based on Cationic Carbon Dots Assembling with 5-Aminolevulinic Acid.

Carbon dots (CDs) with positive surface charges are considered one of the encouraging nanomedications for antibacterial applications. However, due to the distinctive membrane structure of Gram-negative bacteria, cationic CDs with relatively high concentrations are usually required for effective treatment, which might bring out serious safety issues at high doses. Therefore, it is of substantial significance to improve the killing efficiency of cationic CDs on Gram-negative bacteria at appropriately low concentrations. In this work, optimized cationic CDs (bPEI25 000-CDs) were prepared via a hydrothermal method with citric acid and branched PEI25000, which offered a positive surface potential, elimination abilities against Escherichia coli, and relatively high biosafety. The optimized bPEI25 000-CDs can further assemble with the clinical photodynamic therapy (PDT) drug 5-aminolevulinic acid (5-ALA) through electrostatic interaction. Moreover, compared with bPEI25 000-CDs and 5-ALA, the bacterial survival rate was significantly reduced by the ALA-bPEI25 000-CD-induced PDT effect. Even when the dose of bPEI25 000-CD carrier was halved, the bacterial survival could be reduced by 44.4% after light exposure compared to those incubated in the dark. The investigation of the bacterial morphology, membrane potential, and intracellular ROS production suggested that the enhanced antibacterial activity may be due to the membrane dysfunction and cell damage resulting from the high interaction between positively charged ALA-bPEI25 000-CDs and the bacterial cell membrane. Meanwhile, the cationic ALA-bPEI25 000-CDs may facilitate the cellular uptake of 5-ALA, resulting in a more efficient PDT effect. In summary, the antibacterial strategy proposed in this study will provide a novel approach for expanding the application of CD-based nanomedications.

Chlorinated paraffins in multimedia during residential interior finishing: Occurrences, behavior, and health risk.

Though with bioaccumulation and toxicity, chlorinated paraffins (CPs) are still high produced and widely utilized in various daily necessities for extender plasticization and flame retardation. CPs can be released during the reprocessing processes of finishing materials and distributed in multi-environmental media. Herein, concentrations and compositions of CPs in four representative media including interior finishing materials, PM10, total suspended particulate (TSP), and dust samples collected from eight interior finishing stages were studied. Unexpectedly, CP concentrations in ceramic tiles was found to be high with a mean value of 7.02 × 103 µg g-1, which could be attributed to the presence of CPs in the protective wax coated on ceramic tiles surfaces. Furthermore, the pollution characteristics of short-chain and medium-chain CPs (SCCPs and MCCPs) in those samples were inconsistent. According to the investigation regarding Kdust-TSP and [Formula: see text] , the occurrence and distribution of CPs in indoor atmospheric particles (PM10 and TSP) and dust were highly affected by reprocessing processes (cutting, hot melting, etc.) compared to that in the finishing materials. Moreover, dermal contact was the primary pathway of CP exposure for the occupational population (interior construction workers) for most interior finishing stages, and the interior finishing process is the prime CP exposure period for the occupational groups. As suggested by our assessment, though hardly posing an immediate health risk, CPs exposure still presents unneglected adverse health effects, which calls for adequate personal protections during interior finishing, especially in developing countries.

Danggui Buxue decoction alleviates cyclophosphamide-induced myelosuppression by regulating ß-hydroxybutyric acid metabolism and suppressing oxidative stress.

CONTEXT: Danggui Buxue Decoction (DBD) is an effective complementary medicine in alleviating myelosuppression after chemotherapy (MAC). However, its mechanism of action is elusive. OBJECTIVE: To illustrate that regulating ß-hydroxybutyric acid (ß-OHB) metabolism and suppressing oxidative stress could be a potential mechanism of action for DBD in alleviating MAC. MATERIALS AND METHODS: After HPLC quantification and dose testing (3, 6 and 10 g/kg, gavage) of DBD, Sprague-Dawley rats were divided into control, cyclophosphamide (CTX) (30 mg/kg CTX for 5 days, intraperitoneal administration) and CTX + DBD groups (6 g/kg DBD for 14 days, gavage). Blood cell counts, thigh bone histological examination, ß-OHB levels, oxidative stress indices and HDAC1 activity were tested. The biological function of ß-OHB was verified in vitro (hBMSC cells were incubated in culture mediums that contained 40 µM CTX and ß-OHB in 0, 1, 2.5, 5, 10 mM) and in vivo (MAC rat model, 3 g/kg ß-OHB for 14 days, gavage). RESULTS: Rats in the CTX + DBD group showed upregulated blood cell counts (118-243%), ß-OHB levels (495 nmol/mL in blood, 122 nmol/mg in marrow supernatant) and downregulated HDAC1 activity (59%), and oxidative stress indices (60-85%). In vitro, 5 mM ß-OHB improved hBMSC cell migration (123%) and proliferation (131%). In vivo, rats treated with 3 g/kg ß-OHB showed upregulated blood cell counts (121-182%) and downregulated HDAC1 activity (64%) and oxidative stress indices (65-83%). DISCUSSION AND CONCLUSIONS: DBD, a traditional Chinese medicine, alleviates MAC by intervening in ß-OHB metabolism and oxidative stress.

The neglected potential source of microplastics from daily necessities: A study on protective mobile phone cases.

Microplastics (MPs) pollution has become a serious global environment problem. It is therefore of practical significance to investigate the MP pollution caused by using plastic materials on a daily basis. In this study, different protective mobile phone cases (PMPCs) were selected as a representative plastic commodity that are in contact with the human body for long periods to explore the generation and transportation of MPs during 3 months of actual use. The average abundances were 1122 particles cm-2 on the PMPC and 314 particles cm-2 on the palm, respectively. There were four main kinds of MPs produced during the use of different PMPCs, which indicated that waste plastics may be recycled and used as raw materials, resulting in a complex PMPC composition. The median sizes of MPs on the surfaces of PMPCs and palms were 28 and 32 µm, respectively, which were smaller than the sizes reported in other studies. The combined effect of ultraviolet ageing and friction was the main reason for MP generation during daily PMPC use. Based on the results of a fitted regression equation and Monte Carlo simulation, the sharply generation of MPs may occur when PMPC was used for approximately 33 days.

The impact of three related emission industries on regional atmospheric chlorinated paraffins pollution.

Identifying the contributions of various chlorinated paraffins (CPs) sources in the environment plays an important practical role in the prevention and control of the CPs contamination. However, little is known about how main CP-related emission industries affect the regional atmospheric characteristics of CPs, including CP products industry, metal working industry, and polyvinyl chloride (PVC) industry. In this study, 60 passive air samples were collected from five typical cities in Henan Province, China, which had serious CP pollution and different structures of CP-related emission industry. Short chain CPs (SCCPs) and medium chain CPs (MCCPs) were detected in all samples in concentrations ranging of 2.6-7.7 × 102 and 2.1-4.3 × 102 ng m-3, respectively, which were higher than those in most reports. Moreover, Luoyang (LY) is different from other cities, showing a relatively severe MCCP contaminations. The CP pollution characteristics between different cities are obviously affected by the proportion of local CP-related industries. According to the results of cluster heatmaps, the local CP-related emission industrial structure had a greater impact on MCCPs pollution than SCCPs. Additionally, the contribution of metal working industry was beyond that of PVC production industry and CP products industry.

Insights into Persistent Toxic Substances in Protective Cases of Mobile Phones: Occurrence, Health Risks, and Implications.

Despite the popularity of smartphones worldwide, persistent toxic substances (PTSs) in protective cases of mobile phones (PCMPs) and their health risks via direct skin contact have been ignored. This study investigated PTSs in PCMPs made in China with different materials and sales territory and their potential harm to human health. Polybrominated diphenyl ethers (PBDEs, 6.40 ng/g), new brominated flame retardants (NBFRs, 144 ng/g), organophosphate esters (OPEs, 10.1 µg/g), short-chain chlorinated paraffins (SCCPs, 3.58 µg/g), medium-chain chlorinated paraffins (MCCPs, 3.17 µg/g), and heavy metals (HMs, 72.3 µg/g) were detected. It was found that the different concentrations and compositions depend on the material, region, and use. Moreover, the raw materials used to fabricate PCMPs are of variable quality and may include recycled plastic waste. There are no standard quality specifications for PCMPs, and different materials have different properties, including specific surface area and adsorption ability. The risk assessment performed by Monte Carlo simulations indicated that the PTSs evaluated pose no health risks to the general population and may have adverse effects on individual high-exposure populations. According to the results of this work, it is suggested that more stringent global specifications for the selection of raw materials should be established, including the content and structural characteristics of PTSs, limitations on the use of additives in the production process, and the handling after use.

Fluorometric determination of ssDNA based on functionalized magnetic microparticles and DNA supersandwich self-assemblies.

A method is described for the determination of DNA via nucleic acid amplification by using nucleic acid concatemers that result from DNA supersandwich self-assemblies (SSAs). The method employs two auxiliary probes to form self-assembled biotin SSAs. These exhibit strong fluorescence if labeled with intercalator SYBR Green I. In the presence of the target (as exemplified for a 30-mer), streptavidin is released from the surface of the functionalized magnetic microparticles (FMMPs) by competitive hybridization on the surface. However, the SSA products do not conjugate to the FMMPs. This leads to a large amount of SYBR Green I intercalated into the concatemers and eventually results in amplified fluorescence in the supernate. The SSA products can be prepared beforehand, and amplification therefore can be completed within 50 min. The method is more efficient than any other conventional amplification. The detection limit for the 30-mer is 26.4 fM which is better by a factor of 10 compared to other amplification methods. Conceivably, the method can be further extended to the determination of a wide variety of targets simply by replacing the sequences of the probes. Finally, this rapid and highly sensitive method was employed for detection of Ebola virus gene (≈30-mer) and ATP in spiked serum with satisfactory results. Graphical abstract A high sensitivity and efficiency bioassay is described based on functionalized magnetic microparticles and DNA supersandwich self-assemblies.

Colorimetric and fluorescent dual-mode detection of microRNA based on duplex-specific nuclease assisted gold nanoparticle amplification.

MicroRNAs (miRNAs) are attractive candidates for biomarkers for early cancer diagnosis, and play vital roles in physiological and pathological processes. In this work, we developed a colorimetric and fluorescent dual-mode sensor for miRNA detection based on the optical properties of gold nanoparticles (AuNPs) and the duplex-specific nuclease (DSN)-assisted signal amplification technique. In brief, FAM labelled hairpin probes (HPs) were immobilized on AuNPs, and fluorescence was efficiently quenched by the vicinity of the fluorophores to the AuNPs surface. In the presence of target miRNAs, the HPs could specifically hybridize with miRNAs and the DNA strand in the DNA/RNA heteroduplexes could be subsequently hydrolyzed by DSN. As a result, numbers of fluorophores were released into the solution, resulting in obvious fluorescence signal recovery. Meanwhile, the target miRNAs were able to participate in other hybridization reactions. With the DSN-assisted signal amplification technique, lots of gold nanoparticles were produced with short-chain DNA on their surface, which could aggregate in salt solution and result in a colorimetric detection. The proposed dual-mode strategy offers a sensitive, accurate and selective detection method for miRNAs. One reason is that the stem of the HPs was elaborately designed to avoid hydrolyzation by DSN under optimal conditions, which ensures a relatively low background and high sensitivity. The other is that the dual-mode strategy is more beneficial for enhancing the accuracy and reproducibility of the measurements. Moreover, the unique selective-cutting ability and single-base mismatch differentiation capability of the DSN also give rise to a satisfactory selectivity. This demonstrated that the developed method could quantitatively detect miR-21 down to 50 pM with a linear calibration range from 50 pM to 1 nM, and the analytical assay of target miRNAs in cell lysate samples revealed its great potential for application in biomedical research and clinical diagnostics.

Rapid synthesis of Au/Ag bimetallic nanoclusters with highly biochemical stability and its applications for temperature and ratiometric pH sensing.

Herein, we developed a simple and rapid strategy to synthesize gold/silver bimetallic nanoclusters (Au/Ag NCs) with highly biochemical stability by a one-pot route. The Au/Ag NCs were obtained via a chemical reduction procedure in alkaline aqueous solution at 75 °C within only 20 min by employing bovine serum albumin (BSA) as both ligand and reductant. The as-obtained Au/Ag NCs displayed bright orange fluorescence with an emission peak located at 570 nm and temperature-dependent fluorescence property, which were utilized as fluorescent thermometer directly. More intriguingly, the Au/Ag NCs were very stable against various pH values, ions, biothiols, H2O2, fetal bovine serum (FBS), RPMI 1640 medium and amino acids. Taking advantage of the excellent biochemical stability, a ratiometric fluorescence biosensor, fluorescein-5-isothiocyanate (FITC)-Au/Ag NCs, was constructed for pH sensing based on the incorporation of FITC into the Au/Ag NCs. Furthermore, the ratiometric pH sensor was also successfully applied on the model of HeLa cells.

Cobalt oxyhydroxide modified with poly-ß-cyclodextrin and a cyanine dye as a nanoplatform for two-photon imaging of ascorbic acid in living cells and tissue.

This article describes the development of several nanoconjugates composed of cobalt (III) oxyhydroxide and DEASPI/ßCDP, where DEASPI stands for the dye trans-4-[p-(N,N-diethylamino)styryl]-N-methylpyridinium, and ßCDP stands for ß-cyclodextrin. The material enables sensitive fluorometric detection and 3D imaging of ascorbic acid (AA) in biological samples. A nanomicelle composed of DEASPI and ßCDP was prepared to act as a two-photon absorbance (TPA) nanofluorophore with desirable two-photon-sensitized fluorescence, high penetration depth, and excellent cell-permeability). The CoOOH nanoflakes were placed on the surface of the nanomicelle to act as both a quencher of fluorescence and as the recognition unit for AA. In the presence of AA, the CoOOH nanoflakes are reduced to Co (II), and this triggers the recovery of fluorescence. This new nanoprobe exhibits amplified two-photon fluorescence (excitation at 840 nm; emission at 565 nm), high sensitivity, and good selectivity. In-vitro imaging of endogenous AA was demonstrated in living HeLa cells. It was also employed to 3D imaging of exogenous AA in tissue by two-photon excitation microscopy to a depth of up to 320 µm. In our perception, this nanoprobe represents a valuable tool for elucidating the roles of AA in biochemical and clinical studies. Graphical abstract Schematic presentation of the preparation of a novel Poly ß-Cyclodextrin/TPdye conjugated with cobalt oxyhydroxide nanoplatform and its application for high sensitive and two-photon 3D imaging of ascorbic acid (AA) in living cells and deep tissues.

A fluorometric aptamer-based assay for ochratoxin A using magnetic separation and a cationic conjugated fluorescent polymer.

A fluorometric aptamer-based assay for ochratoxin A (OTA) is described. It is making use of magnetic separation and a cationic conjugated fluorescent polymer. Amino-tagged aptamer (Apt) against OTA is immobilized on magnetic beads (MBs) to form a conjugate of type Apt-MBs. The immobilized aptamer is partially complementary to carboxyfluorescein-labeled DNA which binds to the Apt-MBs via hybridization if OTA is absent. Only few FAM-DNA will remain in the supernatant after magnetic separation, and only weak fluorescence resonance energy transfer (FRET) occurs on addition of the fluorescent polymer. If, however, OTA is present, it will bind to the aptamer and prevent the hybridization between Apt-DNA and FAM-DNA. This results in the presence of large amounts of FAM-DNA in the supernatant after magnetic separation. On addition of fluorescent polymer, efficient FRET occurs from the polymer to FAM-DNA. Fluorescence, best measured at excitation/emission peaks of 370/530 nm, increases with increasing concentrations of OTA. This assay is highly sensitive and selective. The detection limit is as low as 0.11 ng mL-1. This is 6 times lower than the aptamer assay without using the fluorescent polymer. Conceivably, this method has a wider scope in that it may be extended to other mycotoxins by simply changing the aptamer. Graphical Abstract Schematic of a fluorometric aptamer assay for ochratoxin A (OTA). It is based on magnetic separation coupled with a cationic conjugated polymer (PFP).

A cationic conjugated polymer coupled with exonuclease I: application to the fluorometric determination of protein and cell imaging.

A strategy is described for the detection of protein by using a cationic fluorescent conjugated polymer coupled with exonuclease I (Exo I). Taking streptavidin (SA) as model protein, it is observed that Exo I can digest single-stranded DNA conjugated with biotin and carboxyfluorescein (P1) if SA is absent. This leads to the formation of small nucleotide fragments and to weak fluorescence resonance energy transfer (FRET) from the polymer to P1. If, however, SA is present, the high affinity of SA and biotin prevents the digestion of P1 by Exo I. This results in the sorption of P1 on the surface of the polymer through strong electrostatic interaction. Hence, efficient FRET occurs from the fluorescent polymer to the fluorescent label of P1. Fluorescence is measured at an excitation wavelength of 370 nm, and emission is measured at two wavelengths (530 and 425 nm). The ratio of the two intensities (I530/I425) is directly related to the concentration of SA. Under the optimal conditions, the assay has a detection limit of 1.3 ng·mL-1. The method was also applied to image the folate receptor in HeLa cells, thus demonstrating the versatility of this strategy. Graphical abstract A fluorometric strategy is described for protein detection and cell imaging based on a cationic conjugated polymer (PFP) coupled with exonuclease I (Exo I) trigged fluorescence resonance energy transfer (FRET).

Highly Fe3+-Selective Fluorescent Nanoprobe Based on Ultrabright N/P Codoped Carbon Dots and Its Application in Biological Samples.

Measuring the levels of Fe3+ in human body has attracted considerable attention for health monitoring as it plays an essential role in many physiological processes. In this work, we reported a selective fluorescent nanoprobe for Fe3+ detection in biological samples based on ultrabright N/P codoped carbon dots. By employing adenosine 5'-triphosphate (ATP) as the carbon, nitrogen, and phosphorus source, the N/P codoped carbon dots could be simply prepared through hydrothermal treatment. The obtained carbon dots exhibited high quantum yields up to 43.2%, as well as excellent photostability, low toxicity, and water solubility. Because of the Fe-O-P bonds formed between Fe3+ and the N/P codoped carbon dots, this nanoprobe showed high selectivity toward Fe3+ against various potential interfering substances in the presence of EDTA. The fluorescence quenching of as-fabricated carbon dots was observed with the increasing Fe3+ concentration, and the calibration curve displayed a wide linear region over the range of 1-150 µM with a detection limit of 0.33 µM. The satisfactory accuracy was further confirmed with the river samples and ferrous sulfate tablets, respectively. With the above outstanding properties, these N/P codoped carbon dots were successfully applied for direct detection of Fe3+ in biological samples including human blood serum and living cells. As compared to the most reported carbon dots-based Fe3+ sensors, this nanoprobe showed high fluorescence, good accuracy, and excellent selectivity, which presents the potential practical application for diagnosis of Fe3+ related disease.

Polyvalent and Thermosensitive DNA Nanoensembles for Cancer Cell Detection and Manipulation.

Development of smart DNA nanostructures is of great value in cancer studies. Here, by integrating rolling circle amplification (RCA) into split aptamer design, a novel strategy of polyvalent and thermosensitive DNA nanoensembles was first proposed for cancer cell detection and manipulation. In this strategy, a long nanosolo ssDNA with repeated Split-b and Poly T regions was generated through RCA. Split-b supplied polyvalent binding sites while Poly T supported signal output by hybridizing with fluorophore-labeled poly A. After addition of Split-a, nanoensembles formed on the cell surface due to target-induced assembly of Split-a/Split-b from the free state to the recognition structure, and on the basis of the thermosensitivity of split aptamer, nanoensembles were controlled reversibly by changing temperatures. As proof of concept, split ZY11 against SMMC-7721 cancer was used to construct nanoensembles. Compared with monovalent split aptamer, nanoensembles were demonstrated to have a much stronger interaction with target cells, thus realizing an ∼2.8-time increase in signal-to-background ratio (SBR). Moreover, nanoensembles extended the tolerance range of target binding from 4 °C to room temperature and speeded recognition thus achieving almost 50% binding in 1 min. Then, nanoensembles were successfully applied to detect 7721 cells in serum and mixed cell samples. By utilizing microplate well surface as the model, temperature-controlled catch/release of target cells was also realized with nanoensembles, even under unfriendly conditions for monovalent split aptamer. The RCA-mediated aptameric nanoensembles strategy not only solved the problem of split aptamer in inefficient binding but also paved a brand new way for developing polyvalent and intelligent nanomaterials.

Dumbbell DNA-templated CuNPs as a nano-fluorescent probe for detection of enzymes involved in ligase-mediated DNA repair.

DNA repair processes are responsible for maintaining genome stability. Ligase and polynucleotide kinase (PNK) have important roles in ligase-mediated DNA repair. The development of analytical methods to monitor these enzymes involved in DNA repair pathways is of great interest in biochemistry and biotechnology. In this work, we reported a new strategy for label-free monitoring PNK and ligase activity by using dumbbell-shaped DNA templated copper nanoparticles (CuNPs). In the presence of PNK and ligase, the dumbbell-shaped DNA probe (DP) was locked and could resist the digestion of exonucleases and then served as an efficient template for synthesizing fluorescent CuNPs. However, in the absence of ligase or PNK, the nicked DP could be digested by exonucleases and failed to template fluorescent CuNPs. Therefore, the fluorescence changes of CuNPs could be used to evaluate these enzymes activity. Under the optimal conditions, highly sensitive detection of ligase activity of about 1U/mL and PNK activity down to 0.05U/mL is achieved. To challenge the practical application capability of this strategy, the detection of analyte in dilute cells extracts was also investigated and showed similar linear relationships. In addition to ligase and PNK, this sensing strategy was also extended to the detection of phosphatase, which illustrates the versatility of this strategy.

Facile fabrication of a resveratrol loaded phospholipid@reduced graphene oxide nanoassembly for targeted and near-infrared laser-triggered chemo/photothermal synergistic therapy of cancer in vivo.

Resveratrol (Res) has emerged as an extremely promising natural molecule due to its vast therapeutic prospects. However, the potential of the drug is immensely hindered by several limiting factors including poor water solubility, limited chemical stability and high metabolization. Herein we report a facile synthesis of a Res-loaded folate-terminated PEG-phospholipid coated reduced graphene oxide nanoassembly (FA-PEG-Lip@rGO/Res) by simply sonicating Res and rGO in FA-PEG linked liposome (FA-PEG-liposome) suspensions. The as-obtained FA-PEG-Lip@rGO/Res exhibits a nanoscale size (148 ± 7 nm), a negative surface potential (-23.6 mV), an excellent drug loading (69.5 ± 4.3%), a high drug entrapment efficiency (86.9 ± 5.6%), good monodispersity and controlled release. Additionally, the nanoassembly can protect Res from UV-light induced instability. Owing to the folate mediated targeted delivery, the robust FA-PEG-Lip@rGO/Res can deliver loaded Res to human MCF-7 breast cancer cells with high specificity and excellent efficiency. The cell toxicity viability shows that unloaded FA-PEG-Lip@rGO has no cytotoxicity, confirming its suitability as a drug vehicle. Furthermore, a systematic in vivo study shows that, under near-infrared (NIR) laser irradiation, FA-PEG-Lip@rGO/Res exhibits highly efficient combined chemotherapy and photothermal therapy to eradicate xenografted tumor with a single dose intratumoral (i.t.) injection. Thus, a facile, stable, biocompatible, and highly-effective Res delivery system has been developed, which may greatly advance the application of Res in biomedical research.

Vertically Ordered Mesoporous Silica Film-Assisted Label-Free and Universal Electrochemiluminescence Aptasensor Platform.

Herein, a simple, facile, and label-free electrochemiluminescence (ECL) aptasensor platform was constructed by integration of aptamer-gated systems and vertically ordered mesoporous silica films (MSFs) grown in suit of indium-tin oxide (ITO) electrode. In this aptasensor platform, aptamer could be effectively adsorbed on the surface of aminated MSFs by noncovalent electrostatic attraction and then employed as an ideal gate material to control the blocking and releasing of luminescence reagents (Ru(bipy)32+) entrapped within the pores of MSFs. In the presence of target, the specific aptamer-target binding could trigger the uncapping the pores, releasing the Ru(bipy)32+ with detectable reduced of ECL signal. The feasibility and universality of this design was validated by employing three aptamers that bind to lysozyme, adenosine, and K+ as gate materials, and the detection limits were determined to be 0.06 nM, 0.75 nM, and 0.5 µM, respectively. This ECL aptasensor, based on the simple competitive procedure, was simple design, undemanding, and fast in operation. In addition, no other chemical modification of the aptamer was required, suggesting that this ECL aptasensor could be applied to many other target detections just by altering the aptamer sequence.

Synthesis of Hollow Mesoporous Silica Nanorods with Controllable Aspect Ratios for Intracellular Triggered Drug Release in Cancer Cells.

Here, we have reported a straightforward and effective synthetic strategy for synthesis of aspect-ratios-controllable mesoporous silica nanorods with hollow structure (hMSR) and its application for transcription factor (TF)-responsive drug delivery intracellular. Templating by an acid-degradable nickel hydrazine nanorods (NHNT), we have first synthesized the hollow dense silica nanorods and then coated on a mesoporous silica layer. Subsequently, the dense silica layer was removed by the surface-protected etching method and the hollow structure of hMSR was finally formed. The aspect ratios of the hMSR can be conveniently controlled by regulating the aspect ratios of NHNT. Four different hMSR with aspect ratios of ca. 2.5, ca. 5.3, ca. 8.1, and ca. 9.0 has been obtained. It was demonstrated that the as-prepared hMSRs have good stability, high drug loading capacity, and fast cell uptake capability, which makes them to a potential nanocarrier for drug delivery. As the paradigm, hMSR with an aspect ratio of ca. 8.1 was then applied for TF-responsive intracellular anticancer drug controlled release by using a Ag(+)-stabilized molecular switch of triplex DNA (TDNA) as capping agents and probes for TFs recognition. In the presence of TF, the pores of hMSR can be unlocked by the TFs induced disassembly of TDNA, leading to the leakage of DOX. The research in vitro displayed that this system has a TFs-triggered DOX release, and the cytotoxicity in L02 normal cells was lower than that of HeLa cells. We hope that this developed hMSR-based system will promote the development of cancer therapy in related fields.

Label-Free Carbon-Dots-Based Ratiometric Fluorescence pH Nanoprobes for Intracellular pH Sensing.

Measuring pH in living cells is of great importance for better understanding cellular functions as well as providing pivotal assistance for early diagnosis of diseases. In this work, we report the first use of a novel kind of label-free carbon dots for intracellular ratiometric fluorescence pH sensing. By simple one-pot hydrothermal treatment of citric acid and basic fuchsin, the carbon dots showing dual emission bands at 475 and 545 nm under single-wavelength excitation were synthesized. It is demonstrated that the fluorescence intensities of the as-synthesized carbon dots at the two emissions are pH-sensitive simultaneously. The intensity ratio (I475 nm/I545 nm) is linear against pH values from 5.2 to 8.8 in buffer solution, affording the capability as ratiometric probes for intracellular pH sensing. It also displays that the carbon dots show excellent reversibility and photostability in pH measurements. With this nanoprobe, quantitative fluorescence imaging using the ratio of two emissions (I475 nm/I545 nm) for the detection of intracellular pH were successfully applied in HeLa cells. In contrast to most of the reported nanomaterials-based ratiometric pH sensors which rely on the attachment of additional dyes, these carbon-dots-based ratiometric probes are low in toxicity, easy to synthesize, and free from labels.

Nucleic acid tool enzymes-aided signal amplification strategy for biochemical analysis: status and challenges.

Owing to their highly efficient catalytic effects and substrate specificity, the nucleic acid tool enzymes are applied as 'nano-tools' for manipulating different nucleic acid substrates both in the test-tube and in living organisms. In addition to the function as molecular scissors and molecular glue in genetic engineering, the application of nucleic acid tool enzymes in biochemical analysis has also been extensively developed in the past few decades. Used as amplifying labels for biorecognition events, the nucleic acid tool enzymes are mainly applied in nucleic acids amplification sensing, as well as the amplification sensing of biorelated variations of nucleic acids. With the introduction of aptamers, which can bind different target molecules, the nucleic acid tool enzymes-aided signal amplification strategies can also be used to sense non-nucleic targets (e.g., ions, small molecules, proteins, and cells). This review describes and discusses the amplification strategies of nucleic acid tool enzymes-aided biosensors for biochemical analysis applications. Various analytes, including nucleic acids, ions, small molecules, proteins, and cells, are reviewed briefly. This work also addresses the future trends and outlooks for signal amplification in nucleic acid tool enzymes-aided biosensors.