Search

Intracellular cysteine (Cys) is an essential element in glutathione (GSH) biosynthesis, which endows cancer cell resistance to various therapies. In this study, we design a Cys metabolism hijacking strategy for converting cytoprotective Cys into therapeutic hydrogen sulfide (H2S), thus achieving enhanced ferroptosis therapy. A therapeutic nanoagent is first synthesized via the co-assembly of L-buthionine-sulfoximine (BSO) and plasmid encoding fn1055 with metal-organic framework (MOF) Fenton catalyst. The encapsulated BSO blocks the Cys-GSH biosynthesis pathway while the Fn1055 protein expressed from plasmid catalyzes the conversion of intracellular Cys to H2S, accelerating Cys-H2S metabolism. Due to its triple functionalities of intracellular acidification, catalase inhibition and mitophagy promotion, H2S significantly accelerates the MOF-induced ferroptosis, which is rationalized by the fully shrunken mitochondria. The in vivo administration of nanoagent effectively suppresses xenograft tumor growth without appreciable side effects. Such Cys metabolism hijacking provides a proof of concept for remolding the Cys-GSH pathway as a promising therapeutic strategy in cancer therapy.

G-quadruplex/hemin (G4/hemin) DNAzymes are biosensing systems, but their application remains limited by an overall low activity and a rather high level of unwarranted background reactions. Here, these issues were addressed through the rational design of F3T-azaC-hemin, a G4-based construct in which the hemin is covalently linked to the G4 core and its binding site flanked with a nucleotide activator, here d(T-azaC). This design led to a G4-DNAzyme whose performances have been ca. 150-fold increased compared to the parent G4-based system. The utility of F3T-azaC-hemin was demonstrated here through the ultrasensitive chemiluminescent detection of miRNA-221. The limit of detection (LOD) has been decreased to the femtomolar range, making it a new and highly efficient molecular tool in the biosensing technology field.

The eclipse-stacked hydrogen-bonded organic framework exhibits ultrafast excited carrier dynamics, thus remarkably accelerates radical annihilation through intrareticular electron coupling pathway for enhanced electrochemiluminescence.

A boron dipyrromethene (BODIPY)-based metal-organic framework (MOF) nanoemitter was for the first time designed with enhanced electrochemiluminescence (ECL) intensity due to the suppression of non-radiative dissipation originating from the ordered arrangement of BODIPY molecules in the framework. Thus, an ECL biosensor was developed for telomerase detection with excellent performance in real samples.

Ferroptosis, a nonapoptotic cell-death pathway, is commonly regulated by ether lipid peroxide generation or glutathione consumption. In this work, a parallel lipid peroxide accumulation strategy was designed based on catalytic metal-organic frameworks (MOFs) for enhanced ferrotherapy. The bimetallic MOF was synthesized with iron porphyrin as a linker and cupric ion as a metal node, and erastin, a ferroptosis inducer, was sandwiched between the MOF layers with 4,4'-dipyridyl disulfide as spacers. In a tumor microenvironment, erastin was released from the layered MOFs through glutathione-responsive cleavage. The exfoliated MOFs served as a dual Fenton reaction inducer to generate numerous hydroxyl radicals for the accumulation of lipid peroxide, while erastin-aggravated glutathione depletion down-regulated glutathione peroxidase 4; this then inhibited the consumption of lipid peroxide. Therefore, a parallel lipid peroxide accumulation strategy was established for enhanced ferrotherapy that effectively inhibited tumor growth in live mice, opening up new opportunities to treat apoptosis-insensitive tumors.

An O2 self-evolving core-shell theranostic nanohybrid was developed by encapsulating a nanoenzyme cerium oxide (CeOx) in a metal-organic framework (MOF). The hybrid reveals a 9-fold higher apoptotic percentage than bare CeOx in a harsh hypoxic microenvironment through tandem homogenous catalysis. Simultaneously, the oxygen-promoted therapeutic efficiency was self-monitored by the hybrid with caspase-3 activation, paving the way for MOF-functionalized nanoenzymes in theranostics.

A transformable upconversion MOF comprising a UCNP core and an azobenzene-based MOF shell is designed for NIR light-modulated chemotherapy. The dual Förster resonance energy transfers (FRETs) involved in this delivery system trigger the transformation of the MOF for drug release and prodrug activation, thus significantly inhibiting the tumor growth and metastasis.

The detection of telomerase is of great significance for monitoring cell canceration. The conventional methods depend on the extension of telomerase towards its primer to conduct signal transduction. Herein, a specific and reliable detection strategy based on stepwise recognition was developed for tandem detection of metal ions and enzymes. We first synthesized an electrically active metal-organic framework (MIL-101(Fe)), which can act directly as a signal reporter in phosphate buffered saline after being modified with capture DNA (cDNA). When the zinc ion is added as a coenzyme factor, the modified hairpin DNA on the electrode is cleaved by DNAzyme to yield the activated primer. After the addition of telomerase, the cleaved DNA strand would be extended, and the resulting sequence will be hybridized with the signal label of MIL-101(Fe)-cDNA. Therefore, a signal-on strategy for the detection of telomerase was achieved based on the direct electrochemical analysis of MIL-101(Fe). Moreover, this electrochemical biosensor can discriminate telomerase activity among different cell lines. The stepwise recognition ensured the advantages of an electrochemical biosensor such as high sensitivity and specificity during the detection process, providing a novel method for monitoring and diagnosis of diseases.

Metal-organic frameworks (MOFs) are an emerging class of molecular crystalline materials built from metal ions or clusters bridged by organic linkers. By taking advantage of their synthetic tunability and structural regularity, MOFs can hierarchically integrate nanoparticles and/or biomolecules into a single framework to enable multifunctions. The MOF-protected heterostructures not only enhance the catalytic capacity of nanoparticle components but also retain the biological activity of biomolecules in an intracellular microenvironment. Therefore, the multifunctional MOF heterostructures have great advantages over single components in cancer therapy. In this review, we comprehensively summarize the general principle of the design and functional modulation of nanoscaled MOF heterostructures, and biomedical applications in enhanced therapy within the last five years. The functions of MOF heterostructures with a controlled size can be regulated by designing various functional ligands and in situ growth/postmodification of nanoparticles and/or biomolecules. The advances in the application of multifunctional MOF heterostructures are also explored for enhanced cancer therapies involving photodynamic therapy, photothermal therapy, chemotherapy, radiotherapy, immunotherapy, and theranostics. The remaining challenges and future opportunities in this field, in terms of precisely localized assembly, maximizing composite properties, and processing new techniques, are also presented. The introduction of multiple components into one crystalline MOF provides a promising approach to design all-in-one theranostics in clinical treatments.

International audience; A high catalytic efficiency associated with a robust chemical structure are among the ultimate goals when developing new biocatalytic systems for biosensing applications. To get ever closer to these goals, we report here on a combination of metal-organic framework (MOF)-based nanozymes and a G-quadruplex (G4)-based catalytic system known as G4-DNAzyme. This approach aims at combining the advantages of both partners (chiefly, the robustness of the former and the modularity of the latter). To this end, we used MIL-53(Fe) MOF and linked it covalently to a G4-forming sequence (F3TC), itself covalently linked to its cofactor hemin. The resulting complex (referred to as MIL-53(Fe)/G4-hemin) exhibited exquisite peroxidase-mimicking oxidation activity and an excellent robustness (being stored in water for weeks). These properties were exploited to devise a new biosensing system based on a cascade of reactions catalyzed by the nanozyme (ABTS oxidation) and an enzyme, the alkaline phosphatase (or ALP, ascorbic acid 2-phosphate dephosphorylation). The product of the latter poisoning the former, we thus designed a biosensor for ALP (a marker of bone diseases and cancers), with a very low limit of detection (LOD, 0.02 U L-1), which is operative in human plasma samples.

Intensive applications of toxic malathion pesticides bring a vital threat to the environment and health. Hence, a credible and sensitive strategy is urgently needed for the respective detection of malathion. In this work, an aptamer-based nonenzymatic autonomous DNA walking machine was fabricated for monitoring trace malathion contamination in cells and foods. Along with the machine walking driven by malathion-triggered reaction entropy, multiple fluorescent signal outputs were thermodynamically generated for signal amplification. The proposed stable DNA nanomachine achieved satisfactory results with a detection limit of 81.9 pg L

Metal-organic frameworks (MOFs) have limited applications in electrochemistry owing to their poor conductivity. Now, an electroactive MOF (E-MOF) is designed as a highly crystallized electrochemiluminescence (ECL) emitter in aqueous medium. The E-MOF contains mixed ligands of hydroquinone and phenanthroline as oxidative and reductive couples, respectively. E-MOFs demonstrate excellent performance with surface state model in both co-reactant and annihilation ECL in aqueous medium. Compared with the individual components, E-MOFs significantly improve the ECL emission due to the framework structure. The self-enhanced ECL emission with high stability is realized by the accumulation of MOF cation radicals via pre-reduction electrolysis. The self-enhanced mechanism is theoretically identified by DFT. The mixed-ligand E-MOFs provide a proof of concept using molecular crystalline materials as new ECL emitters for fundamental mechanism studies.

In this work, a cleancap-regulated aggregation-induced emission (AIE) strategy based on copper nanoclusters (CuNCs) was developed with stepwise recognition for highly specific analysis of the enzyme. The dissolved CuNCs with AIE characteristics in alkaline solution were prepared by using p-mercaptophenylboronic acid as the reducing agent and the stabilizing ligand. The prepared CuNCs can specifically conjugate with glucose (Glu) to connect with each other via the rapid boronate esters formation between boronic acids of CuNCs and a pair of cis-diols on Glu. The cleancap-regulated AIE strategy was further identified by modification of CuNCs with d-glucose 6-phosphate (P-Glu) as the capper and substrate. Introduction of alkaline phosphatase to the P-Glu/CuNCs complex can induce the cleavage of phosphate group to activate the 5,6-diol of Glu on the CuNCs. The decapped complexes could be aggregated through further conjugation between 5,6-diol and boronic acid of two CuNCs, resulting in strong red AIE luminescence. The dual recognitions of enzymatic cleavage and cis-diols/boronic acid conjugation endow the designed method with highly specific detection and cell imaging of enzymatic activity. The cleancap-regulated AIE strategy provides a universal tool for regulation of AIE phenomenon in trace analysis.

Quantification of plasma membrane proteins (PMPs) is crucial for understanding the fundamentals of cellular signaling systems and their related diseases. In this work, a super-quadruplex scaffold was designed to regulate assembly of oligonucleotide-grafted AIEgens for detection of PMPs. The nonfluorescence oligonucleotide-grafted AIEgen (Oligo-AIEgen) was firstly synthesized by attaching the AIEgen to 3′-terminus of the oligonucleotide through click chemistry. Meanwhile, the tetramolecular hairpin-conjugated super-quadruplex (THP-G4) as cleavage element and signal enhancement scaffold composited of three elements: a substrate sequence of DNAzyme in the loop region, partial hybridization region in the stem, and six guanine nucleotides to form G-quadruplex. Once the DNAzyme was anchored on the specific PMPs through aptamer-protein recognition, the substrate sequence on the loop of THP-G4 was cleaved by DNAzyme with the aid of cofactor MnII, resulting in the conformation switch of THP-G4 to the activated G-quadruplex scaffold. The latter could assemble Oligo-AIEgens to generate aggregation-induced emission (AIE) enhancement, resulting in a simple and sensitive strategy for detection of membrane proteins. Moreover, the DNAzyme continuously cut the next THP-G4 to achieve recycling amplification. Under the optimized conditions, this AIE-based strategy exhibited good linear relationship with the logarithm of MUC1 concentration from 0.01 to 10 μg mL−1 with the limit of detection down to 4.3 ng mL−1. The G4-assembled AIEgens provides a universal platform for detecting various biomolecules and a proof-of concept for AIE biosensing.

A host-guest recognition-regulated aggregation-induced emission (AIE) strategy is developed based on the interaction between cyclodextrin-functionalized copper nanoclusters and di(adamantan-1-yl)phosphine as a connector, which significantly improves the AIE efficiency and stability and can be applied to long-term in situ imaging of MUC1 protein.

International audience; Biocatalytic transformations in living cells, such as enzymatic cascades, function effectively in spatially confined microenvironments. However, mimicking enzyme catalytic cascade processes is challenging. Herein, we report a new dual-Hemin-G-quadruplex (dHemin-G4) DNAzyme with high catalytic activity over noncovalent G4/Hemin and monocovalent counterparts (G4-Hemin and Hemin-G4) by covalently linking hemin to both ends of an intramolecular G4. We use MAF-7, a hydrophilic metal-organic framework (MOF), as the protecting scaffold to integrate a biocatalytic cascade consisting of dHemin-G4 DNAzyme and glucose oxidase (GOx), by a simple and mild method with a single-step encapsulation of both enzymes. Such a MAF-7-confined cascade system shows superior activity over not only traditional G4/Hemin but also other MOFs (ZIF-8 and ZIF-90), which was mainly attributed to high-payload enzyme packaging. Notably, the introduction of hydrophilic G4 allows to avoid the accumulation of hydrophobic hemin on the surface of MAF-7, which decreases cascade biocatalytic activity. Furthermore, MAF-7 as protective coatings endowed the enzyme with excellent recyclability and good operational stability in harsh environments, including elevated temperature, urea, protease, and organic solvents, extending its practical application in biocatalysis. In addition, the incorporated enzymes can be replaced on demand to broaden the scope of catalytic substrates. Taking advantages of these features, the feasibility of dHemin-G4/GOx@MAF-7 systems for biosensing was demonstrated. This study is conducive to devise efficient and stable enzyme catalytic cascades to facilitate applications in biosensing and industrial processes.

Coreactant electrochemiluminescence (ECL) is one of the most popular pathways in commercial analysis, which can provide simplicity and convenience for getting intense ECL emission. However, the low efficiency of intermolecular electron transfer could weaken ECL intensity. In this work, we developed an enhanced ECL strategy through in situ coordination interactions between metal-organic framework emitters and coreactants. First, a metal-organic framework (MOF) emitter was synthesized with 1,1,2,2-tetrakis(4-(pyridin-4-yl)phenyl)ethane (TPPE) as aggregation-induced emission linkers and Zn as nodes. Interestingly, compared to TPPE ligand, the resulted MOF nanoemitters demonstrated 49.5 folds enhancement of ECL emission in the presence of 1,4-diazabicyclo[2.2.2]octane (DABCO) as the coreactant. More significantly, different from the constant ECL intensity using TPrA coreactant, DABCO exhibited time-dependent ECL intensity due to the intrareticular electron transfer through coordination interaction between DABCO and Zn

Encapsulation of active biomolecules and/or nanoparticles in metal-organic frameworks (MOFs) remains a great challenge in biomedical applications. In this work, through a stepwise in situ growth method, a black phosphorus quantum dot (BQ) and catalase were precisely encapsulated into the inner and outer layers of MOFs, respectively. The integrated MOF system as a tandem catalyst could convert H2 O2 into O2 in MOF-stabilized catalase outer layer, and then O2 was directly injected into MOF-sensitized BQ inner, leading to high quantum yield of singlet oxygen. Upon internalization, the photodynamic therapy efficiency of the MOF system was 8.7-fold greater than that without catalase, showing an enhanced therapeutic effect against hypoxic tumor cells. Furthermore, by coupling with photothermal therapy of BQs, photodynamic-thermal synergistic therapy was realized both in vitro and in vivo.

Different from conventional DNA walkers, we designed a telomerase-triggered three-dimensional DNA walker consisting of a superhairpin structure with a bulged loop in the stem as the walking strand and dye-labeled tracks for ultrasensitive detection of telomerase activity. In the presence of telomerase, the primers in the stem of the superhairpin structure were elongated and triggered internal strand displacement, thus activating the superhairpin structure. Subsequently, the open superhairpin structure as a swing arm was able to bind with the track, and the swing arm could be released by enzymatic cleavage of the binding duplex domain, resulting in the fluorescence recovery of dye-labeled fragments from the surface of gold nanoparticles. Based on signal amplification of the telomerase-triggered DNA walker, the walking device was further applied to various cancer lines with a low detection limit of telomerase activity equivalent to 90 cells μL-1 for HeLa cells. Moreover, the advantage of this DNA walker strategy was confirmed by calculating telomerase activity in a single cell. This telomerase-triggered DNA walker provides a new concept on signal transduction for telomerase detection and is anticipated to stimulate interest in DNA nanomachine design for bioanalysis.

Distinguishing glutathione (GSH) level in different subcellular locations is critical for studying its antioxidant function in the signaling system. However, traditional methods for imaging subcellular GSH were achieved in isolated organelles or fixed cells. In this work, we report a quencher-delocalized emission strategy for in situ profiling of GSH at different subcellular locations in living cells. A nonemissive metal-organic framework (MOF) nanoprobe was designed with AIEgen as the linker and CuII as the node and quencher. The AIEgen in MOF structure was lightened up with green emission in a neutral environment due to partial CuII delocalization by competitive binding to GSH. Meanwhile, along with the protonation of AIEgen ligand under acidic environment, the AIEgen-based MOF could be completely dissociated in the presence of GSH to yield yellow emission. The two-channel ratiometric analysis of dual-colored emission of AIEgen-based MOF allows visualization of GSH in cytoplasm and lysosome in living cells, which is also able to report the drug effects on different subcellular GSH levels.

The electrochemical reduction of nitric oxide (NO) catalyzed by metal porphyrins as enzyme mimics provides a promising way to understand its roles in biological denitrification. Here, a stepwise electrocatalytic reduction of NO was demonstrated by a cationic picket-fence porphyrin incorporated in an ultrathin phospholipid film. The mass transport-corrected Tafel slopes demonstrated −117 mV/dec and −60 mV/dec for the first and second reduction of NO at physiological pH (pH 7.0), respectively, suggesting a distinguish mechanism for the two-step reduction of NO. More significantly, the potential of the first reduction is constant at −0.37 V vs. NHE while the second potential shifted positively with decreasing pH, giving pH dependence with a slope of −43 mV/pH. A kinetic mechanism of electrocatalytic NO reduction is thus proposed, and provides a promising hint for decoding the functions of the various enzymes. Keywords: Iron porphyrin, Electrocatalysis, Nitric oxide, Kinetic mechanism, Phospholipid

Selecting the timing of laser treatment is an important task for improving O2-dependent photodynamic therapy (PDT) efficiency. Here, a black phosphorus-based strategy was developed for dual-mode monitoring oxygen self-supply, enhancing photodynamic therapy, and feeding back therapeutic effect. The hybridized nanoplatform (R-MnO2-FBP) was prepared by assembly of Rhodamine B (RhB)-encapsulated manganese dioxide (R-MnO2) as O2 supplier and indicator, and fluorescein isothiocyanate (FITC)-labelled peptide-functionalized black phosphorus as the theranostic agent. The time-dependent assays suggested that the O2 release was proportional to the liberation of Mn2+ and RhB in the R-MnO2-FBP system. After specific delivery into cancer cells, R-MnO2-FBP was dissociated in the acidic and H2O2-rich environment and generated oxygen to overcome hypoxia-associated PDT resistance. In the meantime, it released both Mn2+and RhB dye, leading to dual-mode (magnetic resonance imaging/fluorescence imaging) monitoring of the oxygen self-supply process. More significantly, the imaging-guided PDT in hypoxic cells displayed 51.6% of cell apoptosis at optimizing timing of laser application, which could also be confirmed by the FITC fluorescence recovery induced by the activated caspase-3 in apoptotic cells. In vivo photonic therapy by R-MnO2-FBP further demonstrated the ability of R-MnO2-FBP to choose the timing of laser application, providing an efficient approach for the enhancement of PDT process.

In this work, we designed an integrated photoelectrochemical (PEC) analytical system with photovoltage-regulated electrochromic tablet for visualized sensing. The electrochromic tablet consisted of electron-injector (EI) part and colorimetric system, which was functionalized with dye-sensitized titanium dioxide and nickel oxide nanosheet film as the recognition element and signal readout, respectively. Under irradiation of home-built white light, the EI part provided sufficient and stable photovoltage and injected the photoexcited electrons to nickel oxide nanosheet through the conductive inner side of indium tin oxide slide. Thus, the different color states of nickel oxide nanosheet were observed, resulting in a detectable signal by naked eyes for visual analysis. More importantly, the color change was identified to be dependent on the photovoltages generated from EI part. Using copper ions as a model analyte, the electrochromic tablet was successfully applied to visually detect copper ions based on its quenching effect on photovoltage due to the formation of exciton trapping. As a result, the copper ions could be simultaneously determined over a wide range through photovoltage record, average RGB value, and naked eyes. Furthermore, the device exhibited considerable stability and could be reused through simple washing steps. The smart tablet PEC system provides a new avenue to design practical PEC sensor in point-of-care diagnosis.

A plasma-assisted combustion test platform for annular combustor was developed to validate the feasibility of using plasma-assisted combustion actuation to reduce emission levels. Combustor outlet temperature and emission levels of O2, CO2, H2, CO, and NOx were measured by using a thermocouple and a Testo 350-Pro Flue Gas Analyzer, respectively. Combustor combustion efficiency was also calculated. The effects of duty ratio, feedstock air-flow rate, and actuator position on combustion efficiency and emission performance have been analyzed. The results show that the target of CO and NOx emissions reduction in plasma-assisted combustion could not be fully achieved for kerosene/air mixture with different combustor excessive air coefficients. It is also shown that plasma-assisted combustion with dilution air hole actuation is superior to that of secondary air hole actuation for the combustion of liquid-kerosene fuel. Besides, plasma-assisted combustion effect is more obvious with an increase of duty ratio or feedstock air-flow rate. These results are valuable for the future optimization of kerosene-fueled aero-engine when using plasma-assisted combustion devices to improve emission performance of annular combustor.

A direct electrochemistry of silver nanoparticles (AgNPs)-anchored metal-organic frameworks (MOFs) is developed for detection of telomerase activity based on allosteric activation of an aptamer hairpin. AgNPs in situ decorated on PCN-224 (AgNPs/PCN-224) constituted the direct electrochemical labels that were further biofunctionalized by recognition moiety of streptavidin (SA). To achieve the target biosensing, an allosteric hairpin-structured DNA was elaborately designed for signal transduction. The presence of telomerase elongated its primer in the hairpin to displace partial stem strand, thus resulted in the formation of SA aptamer-open structure. Through the specific interaction with aptamer, SA-biofunctionalized AgNPs/PCN-224 probe was attached onto the electrode surface, generating electrochemical signal at + 0.072 V of AgNPs centralized by MOF structure. The direct electrochemical biosensor showed target activity-dependent response from 1.0 × 10−7 to 1.0 × 10−1 IU L−1 with a detection limit of 5.4 × 10−8 IU L−1. Moreover, the sensor was applied in evaluation of telomerase activity in living cancer cells. The established electrochemical detection approach in this work avoids the critical deoxygenation conditions and additional electrocatalytic reagents, which opens a novel biosensing perspective for direct electrochemistry of MOF-based nanocomposites.

The precise release of drugs is essential to improve cancer therapeutic efficacy. In this work, a tandem responsive strategy was developed based on a triple-layered metal-organic framework (MOF) hybrid. The MOF nanoprobe was stepwise fabricated with a telomerase-responsive inner, a pH-sensitive MOF filling and H2 O2 -responsive coordination complex shell of Fe3+ and eigallocatechin gallate (EGCG). In the tumor microenvironment, the shell was dissociated by endogenous H2 O2 and simultaneously produced highly reactive hydroxyl radicals by a Fenton reaction. Meanwhile, the released EGCG could downregulate the expression of P-glycoprotein responsible for drug resistance. After the dissociation of the framework by protons, telomerase could trigger the release of the drug from the DNA duplex on the exposed inner shell. By integrating confined drug release, inhibited efflux pump and chemodynamic therapy, the all-in-one chemotherapy strategy was identified with enhanced therapeutic efficacy in drug-resistant cancer cells.

The demand for transporting coreactant to emitter and short lifetime of the radicals in electrochemiluminescence (ECL) emission inhibit greatly its application in cytosensing and microscopic imaging. Herein we designed a dual intramolecular electron transfer strategy and tertiary amine conjugated polymer dots (TEA-Pdots) to develop a coreactant-embedded ECL mechanism and microimaging system. The TEA-Pdots could produce ECL emission at +1.2 V without need of coreactant in test solution. The superstructure and intramolecular electron transfer led to unprecedented ECL strength, which was 132 and 45 times stronger than those from the mixture of Pdots with TEA at equivalent and 62.5 times higher amounts, respectively. The ECL efficiency was even higher than that of typical [Ru(bpy)3 ]2+ system. Therefore, this strategy and coreactant-embedded ECL system could be used for in situ ECL microimaging of membrane protein on single living cells without additional permeable treatment for transporting coreactant. The feasibility and validity were demonstrated by evaluating the specific protein expression on cell surface. This work opens new avenues for ECL applications in single cell analysis and dynamic study of biological events.

Cancer stem cells (CSCs) possess self-renewal and clonal tumor initiation capacities, which lead to drug resistance and tumor recurrence. In this work, a hypoxia-stimulated strategy based on a smart triblock vector was developed to enhance therapeutic efficacy through the inhibition of cancer stemness. The triblock precursor was designed with a fluorescence chromophore for monitoring hypoxia, a methoxy nitro-unit for biorecognition, and a poly(ethylene glycol)-folate for cancer cell targeting. As the degree of hypoxia increases, the vectors were progressively dissociated as indicated by the enhanced fluorescence intensity in hypoxic cells and compacted three-dimensional spheres. Furthermore, the expression of stem cell markers such as CD133 and SOX2 was significantly inhibited, and the serial passaging of CSCs was notably impaired after treating CSCs with the vectors. The inhibition of cancer cell stemness significantly improved the anticancer efficiency in vivo. Moreover, tumor initiation was reduced and the median survival time of xenograft tumor models was prolonged by regulating cell stemness under hypoxia. Overall, this work provides a promising approach to inhibit tumor resistance and recurrence for efficient tumor therapy.

Nonspecific distribution of photosensitizer and the intrinsic hypoxic condition in the tumor microenvironment are two key factors limiting the efficacy of O2-dependent photodynamic therapy (PDT). Herein, a dual-triggered oxygen self-supported nanosystem using black phosphorus nanosheet (BPNS) as both photosensitizer and nanocarrier was developed to enhance PDT for tumors within hypoxic microenvironment. The BPNS platform was functionalized with folate and a blocker DNA duplex of 5'-Cy5-aptamer-heme/3'-heme labeled oligonucleotides. The resulting heme dimer could passivate its peroxidase activity. After specific recognition of aptamer-target, the quenched fluorescence is "turned" on by cellular adenosine triphosphate. The passivated nanosystem then activates the catalytic function towards excessive intracellular H2O2 to generate O2 essential to sustain BPNS-mediated PDT, leading to 8.7-fold and 7.5-fold increase of PDT efficacy in treating the hypoxic cell and tumor, respectively. Therefore, the dual-triggered oxygen self-supply nanosystem not only exerts tumor microenvironment-associated stimulus for enhanced PDT but also surmounts hypoxia-associated therapy resistance.

A pixel counting strategy is designed on the basis of DNA walker-triggered fluorescence spots for ultrasensitive detection of nucleic acid. The two-dimensional DNA walker was constructed by hybridization of two types of capture DNAs, which were covalently modified by click chemistry on a glass slide, and dye-labeled hairpin structure (hDNA) as track and swing strand (sDNA) as DNAzyme, respectively. Introduction of target DNA unlocked the sDNA via strand displacement to form the activated DNAzyme, and the latter cut nearby hDNA with Mn2+ as cofactor, resulting in fluorescence recovery of dye-labeled hDNA on the substrate due to the separation from the quencher. Meanwhile, the DNAzyme sequence of sDNA was released to cut the next hDNA and, thus, initiated autonomous walking of sDNA for signal amplification. The enhanced fluorescence spots were digitalized as pixels on the basis of DNA walker-built compartments and extracted by a homemade program in MATLAB. The association between fluorescent pixel numbers a...

A core-shell nanostructure is fabricated with a pH-sensitive metal-organic framework shell and a peptide functionalized gold nanoparticle core via a mild synthetic route. The nanostructure can be applied as a dual-recognition switch in response to an acidic environment and enzyme activity, sequentially, leading to a stepwise-responsive strategy for imaging lysosomal cathepsin B.

A flowerlike nanovector is developed for the fluorescence imaging and detection of miRNA in live cells with catalytic hairpin assembly. This horned vector provides a high loading efficiency of DNA amplifiers for multiple signal outputs and is applied to detect miRNA-21 in an average single HeLa cell, showing promising application in trace detection of intracellular biomolecules.

Respiratory supporting, as an important medical treatment for new coronavirus pneumonia patients, must be effectively guaranteed by medical oxygen supply. However, the medical oxygen system designed and configured by the existing hospitals according to the current specifications cannot meet the oxygen needs for patients with new coronavirus pneumonia. This paper aimed to study the design of medical oxygen system in new coronavirus pneumonia emergency hospital. By investigating the oxygen treatment plan for the novel coronavirus pneumonia patients in the health emergency hospital, the oxygen treatment characteristics of different patients were studied. The oxygen characteristics of different respiratory support terminals were explored to study the oxygen demands of new coronavirus pneumonia emergency hospitals. Through calculating flow rates of medical gas system air source referring to ‘technical code for medical gases engineering’, the proportion coefficient of severe patients converted into respiratory distress patients was introduced, and the model of calculating flow rates of medical oxygen system air source in emergency hospital was proposed. The cases were verified in a typical health emergency hospital that the developed calculation flow model of medical oxygen source met the demands of hospital oxygen. The outcomes provide a reference for the design and construction of medical oxygen in such health emergency hospitals.

A photochromic sensing platform composing of emeraldine salt of polyaniline (ES-PANI) and titanium dioxide nanoparticles (TiO 2 NPs) for visual detection of trace copper was developed. Under ultraviolet light irradiation, the greenish ES-PANI could be oxidized to dark blue pernigraniline salt by the photo-generated hole of excited TiO 2 NPs. In the presence of Cu 2+ , a light yellow leucoemeraldine salt was visually observed. The overall mechanism of color change was verified to be corresponding to the different redox states of PANI regulated by Cu species during the photochromic process. By integrating the advantages of both photoelectric property and visual detection, the redox reaction-based sensing mechanism led to a good sensitivity and high selectivity in detection of Cu 2+ with the limit of detection of 0.4 μM. Besides the naked eyes, two color recognition methods including reading mean green intensities in Photoshop and recording ultraviolet absorbance in microplate reader were also studied. This method was successfully applied to Cu 2+ detection in human hair, and satisfactory recoveries were achieved. More significantly, this sensing platform was really simple, low-cost and able to detect an array of analytes within several minutes without requiring sophisticated equipment. This photoelectron-regulated colorimetric strategy provides a novel concept for the design of visual sensing platform, and can develop the portable test kits for rapid detection in clinical diagnosis.

A plasma-assisted combustion (PAC) test platform for annular combustor fan-shaped test piece was developed to validate the feasibility of using PAC actuation to enhance annular combustor performanc...

Encapsulating a large amount of electrochemiluminescence (ECL) active molecules into one nanoparticle for single-target recognition can greatly improve the sensitivity of the ECL assay. This work used luminescent conjugated polymer as a carrier to synthesize Ru(bpy)32+-doped polymer dots (RuPdots). The RuPdots with an average size of 20 nm and encapsulation of about 1354 Ru(bpy)32+ showed greatly enhanced ECL emission. Using tripropylamine as a coreactant, the resonance energy transfer from the excited polymer dots to the encapsulated Ru(bpy)32+ was demonstrated, which led to a 15.7-fold higher ECL emission than that of Ru(bpy)32+ with the same amount at the gold electrode. By coupling the double-enhanced ECL signal of this nanostructure with the specific ligase detection reaction, a sensitive ECL biosensor was constructed for specific detection of a single-nucleotide polymorphism (SNP). Using mutant KRAS gene as a model target, the ECL SNP detection method showed a linear range from 1 fM to 1 nM and a de...

To reveal the basement-involved faults and deep structures of the West Philippine Basin (WPB), the gravitational responses caused by these faults are observed and analyzed based on the latest spherical gravity model: WGM2012 Model. By mapping the free-air and Bouguer gravity anomalies, several main faults and some other linear structures are located and observed in the WPB. Then, by conducting a 2D discrete multi-scale wavelet decomposition, the Bouguer anomalies are decomposed into the first- to eighth-order detail and approximation fields (the first- to eighth-order Details and Approximations). The first- to third-order Details reflect detailed and localized geological information of the crust at different depths, and of which the higher-order reflects gravity field of the deeper depth. The first- to fourth-order Approximations represent the regional gravity fields at different depths of the crust, respectively. The fourth-order Approximation represents the regional gravity fluctuation caused by the density inhomogeneity of Moho interface. Therefore, taking the fourth-order Approximation as input, and adopting Parker-Oldenburg interactive inversion, We calculated the depth of Moho interface in the WPB. Results show that the Moho interface depth in the WPB ranges approximately from 8 to 12 km, indicating that there is typical oceanic crust in the basin. In the Urdaneta Plateau and the Benham Rise, the Moho interface depths are about 14 and 16 km, respectively, which provides a piece of evidence to support that the Banham Rise could be a transitional crust caused by a large igneous province. The second-order vertical derivative and the horizontal derivatives in direction 0° and 90° are computed based on the data of the third-order Detail, and most of the basement-involved faults and structures in the WPB, such as the Central Basin Fault Zone, the Gagua Ridge, the Luzon-Okinawa Fault Zone, and the Mindanao Fault Zone are interpreted by the gravity derivatives.

Integration of a photodynamic therapy platform with a drug-delivery system in a porous structure is an urgent challenge for enhanced anticancer therapy. Here, an amino-functionalized metal–organic framework (MOF), which is useful as efficient delivery vehicle for drugs and provides the −NH2 group for postsynthetic modification, is chosen and well-designed for cell imaging and chemo-photodynamic therapy. The multifunctional MOF nanoprobe was first assembled with camptothecine drug via noncovalent encapsulation and then bound with folic acid as the targeted element and chlorine e6 (Ce6)-labeled CaB substrate peptide as the recognition moiety and signal switch. The designed MOF probe can realize cathepsin B-activated cancer cell imaging and chemo-photodynamic dual-therapy combining Ce6 as the photosensitizer and the camptothecine drug. Compared with the individual treatment, the dual-functional nanoprobe presents an enhanced treatment efficiency in terms of the time of chemotherapy, laser power, and irradiat...