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The process of coordinating between the same or multiple types of cells to jointly execute various instructions in a controlled and carefully regulated environment is a very appealing field. In order to provide clearer insight into the role of cell–cell interactions and the cellular communication of this process in their local communities, several interdisciplinary approaches have been employed to enhance the core understanding of this phenomenon. DNA nanostructures have emerged in recent years as one of the most promising tools in exploring cell–cell communication and interactions due to their programmability and addressability. Herein, this review is dedicated to offering a new perspective on using DNA nanostructures to explore the progress of cell–cell communication. After briefly outlining the anchoring strategy of DNA nanostructures on cell membranes and the subsequent dynamic regulation of DNA nanostructures, this paper highlights the significant contribution of DNA nanostructures in monitoring cell–cell communication and regulating its interactions. Finally, we provide a quick overview of the current challenges and potential directions for the application of DNA nanostructures in cellular communication and interactions. [ABSTRACT FROM AUTHOR]

Covalent proteolysis-targeting chimeras (PROTACs) offer enhanced selectivity, prolonged action, and increased efficacy against challenging target proteins. The conventional approach relies on covalent ligands, but our study presents an innovative method employing an N-sulfonyl pyridone warhead to selectively target tyrosine (Tyr) residues. The von Hippel–Lindau (VHL) moiety is transferred from the warhead to the exposed Tyr, allowing us to design a STING degrader (DC50 0.53 μM, Dmax 56.65%). This approach showcases the potential of nucleophilic amino acid labeling probes, particularly for proteins lacking easily accessible cysteine residues, opening new possibilities for covalent PROTAC design and targeted protein degradation therapies. [ABSTRACT FROM AUTHOR]

The 2-hydroxyethylhydrazinium nitrate ([HOCH2CH2NH2NH2]+NO3−, HEHN) ionic liquid has the potential to power both electric and chemical thrusters and provide a wider range of specific impulse needs. To characterize its capabilities as an electrospray propellant, we report the formation of HEHN cluster ions in positive electrospray ionization (ESI) and their collision-induced dissociation. The experiment was carried out using ESI guided-ion beam mass spectrometry which mimics an electrospray thruster in terms of ion emission, injection into a vacuum and fragmentation in space. Measurements include compositions of primary ions in the electrospray plume and their individual dissociation product ion cross sections and threshold energies. The results were interpreted in light of theoretical modeling. To determine cluster structures that are comprised of [HE + H]+ and NO3− constituents, classical mechanics simulations were used to create initial guesses; and for clusters that are formed by reactions between ionic constituents, quasi-classical direct dynamics trajectory simulations were used to mimic covalent bond formation and structures. All candidate structures were subject to density functional theory optimization, from which global minimum structures were identified and used for construction of reaction potential energy surface. The comparison between experimental values and calculated dissociation thermodynamics was used to verify the structures for the emitted species [(HEHN)nHE + H]+, [(HEHN)n(HE)2 + H]+, [(HE)n+1 + H]+ and [(HE)nC2H4OH]+ (n = 0–2), of which [(HE)1–2 + H]+ dominates. Due to the protic nature of HEHN, cluster fragmentation can be rationalized by proton transfer-mediated elimination of HNO3, HE and HE·HNO3, and the latter two become dominant in larger clusters. [(HE)2 + H]+ and [(HE)nC2H4OH]+ contain H-bonded water and consequently are featured by water elimination in fragmentation. These findings help to evaluate ion formation and fragmentation efficiencies and their impacts on electrospray propulsion. [ABSTRACT FROM AUTHOR]

A novel colorimetric and fluorescent dual-mode sensing system based on molybdophosphoric heteropoly acid (PMA) and fluorescent microspheres (FMs) was established for monitoring the activity of alkaline phosphatase (ALP). In the presence of ALP, L -ascorbic acid-2-phosphate (AAP) could be hydrolyzed catalytically to ascorbic acid (AA), which could reduce PMA to phosphorus molybdenum blue (PMB), accompanied by the generation of colorimetric signals depending on the level of ALP. Meanwhile, the fluorescence of FMs was quenched markedly by the PMB produced due to the inner-filter effect, which constituted the response mechanism for the dual-mode sensing systems of ALP. On this basis, a PMA-FMs based dual-mode sensing system was used for the detection of ALP, which not only possessed remarkable sensitivity, with a limit of detection of 0.27 U L−1 and 0.11 U L−1, but also exhibited good analytical performance in biological samples with satisfactory results. Moreover, a simple and portable test kit for the visual detection of ALP in real serum samples was fabricated utilizing a smartphone with image-recognition and data-processing capabilities as a visual-detection platform. [ABSTRACT FROM AUTHOR]

Coacervate microdroplets, formed via liquid–liquid phase separation, have been proposed as a compartment model for the construction of artificial cells or organelles. However, these microsystems are very fragile and demonstrate liquid-like fluidity. Here, an artificial cytoskeleton based on DNA nanotubes was constructed in coacervate microdroplets to modulate the liquid fluidic properties of the microdroplets. The coacervate microdroplets were obtained from the association of oppositely charged polyelectrolytes through liquid–liquid phase separation, and DNA nanotubes were constructed by molecular tile self-assembly from six clip sequences. The DNA nanotubes were efficiently sequestered in the liquid coacervate microdroplets, and the rigid structure of the DNA nanotubes was capable of modulating the liquid fluidic properties of the coacervate protocell models, as indicated by coalescence imaging and atomic force microscopy analysis. Therefore, artificial cytoskeletons made from DNA nanotubes worked in modulating the liquid fluidic properties of coacervate microdroplets, in a manner akin to the cytoskeleton in the cell. DNA cytoskeletons have the potential to become an ideal platform with which how the liquid fluidic properties of cells are modulated by their cytoskeletons can be investigated, and the cell-sized coacervate microdroplets containing artificial cytoskeletons might be critical in developing a stable liquid-phase protocell model. [ABSTRACT FROM AUTHOR]

Hydroxylammonium nitrate (HAN) is a potential propellant candidate for dual-mode propulsion systems that combine chemical and electrospray thrust capabilities for spacecraft applications. However, the electrospray dynamics of HAN is currently not well understood. Capitalizing on electrospray ionization guided-ion beam tandem mass spectrometry and collision-induced dissociation measurements, and augmented by extensive molecular dynamics simulations, this work characterized the structures and reaction dynamics of the species present in the electrosprays of HAN under different conditions, which mimic those possibly occurring in low earth orbit and outer space. While being ionic in nature, the HAN monomer, however, adopts a stable covalent structure HONH2·HNO3 in the gas phase. Spontaneous proton transfer between the HONH2 and HNO3 moieties within the HAN monomer can be induced in the presence of a NO3−, a water ligand or a second HAN monomer within 3–5 Å or a H+ within 8 Å, regardless of their collision impact parameters. These facts imply that HAN proton transfer is trigged by a charge and/or a dipole of the collision partner without the need of chemical interaction or physical contact. Moreover, the addition of NO3− to HAN leads to the formation of a stable −O3N·HONH3+·NO3− anion in negative electrosprays. In contrast, when a proton approaches the HONH2·HNO3 structure, dissociative reactions occur that lead to the H2O, NO2 and HONH2 fragments (and their cations) but not intact HAN species in positive electrosprays. [ABSTRACT FROM AUTHOR]

It has been shown previously in protonated, deprotonated and ionized guanine–cytosine base pairs that intra-base pair proton transfer from the N1–H at the Watson–Crick edge of guanine to the complementary nucleobase prompts non-statistical dissociation of the base-pair system, and the dissociation of a proton-transferred base-pair structure is kinetically more favored than that of the starting, conventional base-pair structure. However, the fundamental chemistry underlying this anomalous and intriguing kinetics has not been completely revealed, which warrants the examination of more base-pair systems in different structural contexts in order to derive a generalized base-pair structure–kinetics correlation. The purpose of the present work is to expand the investigation to the non-canonical homodimeric and heterodimeric radical cations of 9-methylguanine (9MG) and 9-methyl-8-oxoguanine (9MOG), i.e., [9MG·9MG]˙+, [9MOG·9MG]˙+ and [9MOG·9MOG]˙+. Experimentally, collision-induced dissociation tandem mass spectrometry coupled with an electrospray ionization (ESI) source was used for the formation of base-pair radical cations, followed by detection of dissociation product ions and cross sections in the collisions with Xe gas under single ion–molecule collision conditions and as a function of the center-of-mass collision energy. Computationally, density functional theory and coupled cluster theory were used to calculate and identify probable base-pair structures and intra-base pair proton transfer and hydrogen transfer reactions, followed by kinetics modeling to explore the properties of dissociation transition states and kinetic factors. The significance of this work is twofold: it provides insight into base-pair opening kinetics in three biologically-important, non-canonical systems upon oxidative and ionization damage; and it links non-statistical dissociation to intra-base pair proton-transfer originating from the N1–H at the Watson–Crick edge of 8-oxoguanine, enhancing understanding towards the base-pair fragmentation assisted by proton transfer. [ABSTRACT FROM AUTHOR]

Liquid coacervate microdroplets have been widely explored as membrane-free compartment protocells for cargo delivery in therapeutic applications. In this study, coacervate protocells were developed as gene carriers for transfection of nitric oxide synthase (NOS) and overproduction of nitric oxide (NO) for killing of cancer cells. The coacervate microdroplet protocells were formed via the liquid–liquid phase separation of oppositely charged diethylaminoethyl–dextran/polyacrylic acids. The coacervate microdroplet protocells were found to facilitate gene transfection, which was demonstrated by cell imaging of the internalized coacervate microdroplets containing plasmids of enhanced green fluorescent protein. Due to their high transfection capability, the coacervate protocells were subsequently utilized for the delivery of NOS plasmids (pNOS). The cellular internalization of pNOS-containing coacervate carriers was found to result in high NOS expression coupled with NO overproduction, which then induced cell apoptosis and decreased cell viability. The cell apoptosis is associated with NO-mediated mitochondrial damage. The enhanced gene transfection was attributed to coacervate microdroplets' unique high sequestration capability and liquid-like fluidity. Overall, the incorporation of genes in coacervate microdroplets was demonstrated as a viable and novel strategy for the development of cargo biocarriers for biomedical applications. [ABSTRACT FROM AUTHOR]

In contrast to their spontaneous deprotonation in aqueous solution, reactions of guanine and guanosine radical cations with water in the gas phase are exclusively initiated by hydration of the radical cations as reported in recent work (Y. Sun et al., Phys. Chem. Chem. Phys., 2018, 20, 27510). As gas-phase hydration reactions closely mimic the actual scenario for guanine radical cations in double-stranded DNA, exploration of subsequent reactions within their water complexes can provide an insight into the resulting oxidative damage to nucleosides. Herein guided-ion beam mass spectrometry experiment and direct dynamics trajectory simulations were carried out to examine prototype complexes of the 9-methylguanine radical cation with one and two water ligands (i.e., 9MG˙+·(H2O)1–2) in the gas phase, wherein the complexes were activated by collisional activation in the experiment and by thermal excitation at high temperatures in the simulations. Guided by mass spectroscopic measurements, trajectory results and reaction potential energy surface, three reaction pathways were identified. The first two reaction pathways start with H-atom abstraction from water by the O6 and N7 atoms in 9MG˙+ and are referred to as HAO6 and HAN7, respectively. The primary products of HAO6 and HAN7 reactions, including [9MG + HO6]+/[9MG + HN7]+ and ˙OH, react further to either form [8OH-9MG + HO6]˙+ and [8OH-9MG + HN7]˙+via C8-hydroxylation or form radical cations of 6-enol-guanine (6-enol-G˙+) and 7H-guanine (7HG˙+) via SN2-type methanol elimination. The third reaction pathway corresponds to the formation of 8OH-9MG+ by H elimination from the complex, referred to as HE. Among these product channels, [8OH-9MG + HN7]˙+ has the most favorable formation probability, especially in the presence of additional water molecules. This product may serve as a preceding structure to the 8-oxo-7,8-dihydroguanine lesion in DNA and has implications for health effects of radiation exposure and radiation therapy. [ABSTRACT FROM AUTHOR]

A light-responsive ion transport switch has been developed based on conformation-dependent azobenzene-incorporated lipophilic G-quadruplex channels, which provides a new smart approach for the selective transport of K+ ions across the lipid membrane. [ABSTRACT FROM AUTHOR]

An artificial protocell model mimicking stimuli-triggered extracellular matrix formation is demonstrated based on the self-immobilization of coacervate microdroplets. Endogenous enzyme activity within the microdroplets results in the release of Ca2+ ions that trigger hydrogelation throughout the external environment, which in turn mechanically supports and chemically stabilizes the protocells. [ABSTRACT FROM AUTHOR]

We investigated the collision-induced dissociation (CID) reactions of a protonated Hoogsteen 9-methylguanine–1-methylcytosine base pair (HG-[9MG·1MC + H]+), which aims to address the mystery of the literature reported "anomaly" in product ion distributions and compare the kinetics of a Hoogsteen base pair with its Watson-Crick isomer WC-[9MG·1MC + H]+ (reported recently by Sun et al.; Phys. Chem. Chem. Phys., 2020, 22, 24986). Product ion cross sections and branching ratios were measured as a function of center-of-mass collision energy using guided-ion beam tandem mass spectrometry, from which base-pair dissociation energies were determined. Product structures and energetics were assessed using various theories, of which the composite DLPNO-CCSD(T)/aug-cc-pVTZ//ωB97XD/6-311++G(d,p) was adopted as the best-performing method for constructing a reaction potential energy surface. The statistical Rice–Ramsperger–Kassel–Marcus theory was found to provide a useful framework for rationalizing the dominating abundance of [1MC + H]+ over [9MG + H]+ in the fragment ions of HG-[9MG·1MC + H]+. The kinetics analysis proved the necessity for incorporating into kinetics modeling not only the static properties of reaction minima and transition states but more importantly, the kinetics of individual base-pair conformers that have formed in collisional activation. The analysis also pinpointed the origin of the statistical kinetics of HG-[9MG·1MC + H]+vs. the non-statistical behavior of WC-[9MG·1MC + H]+ in terms of their distinctively different intra-base-pair hydrogen-bonds and consequently the absence of proton transfer between the N1 position of 9MG and the N3′ of 1MC in the Hoogsteen base pair. Finally, the Hoogsteen base pair was examined in the presence of a water ligand, i.e., HG-[9MG·1MC + H]+·H2O. Besides the same type of base-pair dissociation as detected in dry HG-[9MG·1MC + H]+, secondary methanol elimination was observed via the SN2 reaction of water with nucleobase methyl groups. [ABSTRACT FROM AUTHOR]

A guided-ion beam tandem mass spectrometric study was performed on collision-induced dissociation (CID) of a protonated 9-methylguanine–1-methylcytosine Watson–Crick base pair (designated as WC-[9MG·1MC + H]+), from which dissociation pathways and dissociation energies were determined. Electronic structure calculations at the DFT, RI-MP2 and DLPNO-CCSD(T) levels of theory were used to identify product structures and delineate reaction mechanisms. Intra-base-pair proton transfer (PT) of WC-[9MG·1MC + H]+ results in conventional base-pair conformations that consist of hydrogen-bonded [9MG + H]+ and 1MC and proton-transferred conformations that are formed by PT from the N1 of [9MG + H]+ to the N3′ of 1MC. Two types of conformers were distinguished by CID in which the conventional conformers produced [9MG + H]+ product ions whereas the proton-transferred conformers produced [1MC + H]+. The conventional conformers have a higher population (99.8%) and lower dissociation energy than the proton-transferred counterparts. However, in contrast to what was expected from the statistical dissociation of the equilibrium base-pair conformational ensemble, the CID product ions of WC-[9MG·1MC + H]+ were dominated by [1MC + H]+ rather than [9MG + H]+. This finding, alongside the non-statistical CID reported for deprotonated guanine–cytosine (Lu et al.; PCCP, 2016, 18, 32222) and guanine–cytosine radical cation (Sun et al.; PCCP, 2020, 22, 14875), reinforces that non-statistical dissociation is a distinctive feature of singly-charged Watson–Crick guanine–cytosine base pairs. It implies that intra-base-pair PT facilitates the formation of proton-transferred conformers in these systems and the ensuing conformers have loose transition states for dissociation. The monohydrate of WC-[9MG·1MC + H]+ preserves non-statistical CID kinetics and introduces collision-induced methanol elimination via the reaction of the water ligand with a methyl group. [ABSTRACT FROM AUTHOR]

A combined experimental and theoretical study is presented on the collision-induced dissociation (CID) of 9-methylguanine–1-methylcytosine base-pair radical cation (abbreviated as [9MG·1MC]˙+) and its monohydrate ([9MG·1MC]˙+·H2O) with Xe and Ar gases. Product ion mass spectra were measured as a function of collision energy using guided-ion beam tandem mass spectrometry, from which cross sections and threshold energies for various dissociation pathways were determined. Electronic structure calculations were performed at the DFT, RI-MP2 and DLPNO-CCSD(T) levels of theory to identify product structures and map out reaction potential energy surfaces. [9MG·1MC]˙+ has two structures: a conventional structure 9MG˙+·1MC (population 87%) consisting of hydrogen-bonded 9-methylguanine radical cation and neutral 1-methylcytosine, and a proton-transferred structure [9MG − H]˙·[1MC + H]+ (less stable, population 13%) formed by intra-base-pair proton transfer from the N1 of 9MG˙+ to the N3 of 1MC within 9MG˙+·1MC. The two structures have similar dissociation energies but can be distinguished in that 9MG˙+·1MC dissociates into 9MG˙+ and 1MC whereas [9MG – H]˙·[1MC + H]+ dissociates into neutral [9MG – H]˙ radical and protonated [1MC + H]+. An intriguing finding is that, in both Xe- and Ar-induced CID of [9MG·1MC]˙+, product ions were overwhelmingly dominated by [1MC + H]+, which is contrary to product distributions predicted using a statistical reaction model. Monohydration of [9MG·1MC]˙+ reversed the populations of the conventional structure (43%) vs. the proton-transferred structure (57%) and induced new reactions upon collisional activation, of which intra-base-pair hydrogen transfer produced [9MG + H]+ and the reaction of the water ligand with a methyl group in [9MG·1MC]˙+ led to methanol elimination from [9MG·1MC]˙+·H2O. [ABSTRACT FROM AUTHOR]

Coordination-driven suprastructures have attracted much interest due to their unique properties. Among these structures, platinum-based architectures have been broadly studied due to their facile preparation. The resultant two- or three-dimensional (2D or 3D) systems have many advantages over their precursors, such as improved emission tuning, sensitivity as sensors, and capture and release of guests, and they have been applied in biomedical diagnosis as well as in catalysis. Herein, we review the recent results related to platinum-based coordination-driven self-assembly (CDSA), and the text is organized to emphasizes both the synthesis of new metallacycles and metallacages and their various applications. [ABSTRACT FROM AUTHOR]

Synergetic effects in Au–Ag bimetallic nanoclusters (BNCs) more favorably enhanced electrochemical redox induced electrochemiluminescence (ECL) over photoexcitation induced photoluminescence (PL); this not only led to Au–Ag BNCs with enhanced bandgap-engineered ECL compared to Au NCs, but it also generated surface-defect related ECL to enhance the total ECL intensity. [ABSTRACT FROM AUTHOR]

A self-assembled DNA nanostructure based on a DNA nanocreeper and multiplexed fluorescence supersandwich was designed for the sensitive and specific detection of tumour cells. This nanostructure could improve the binding affinity of current aptamers and trigger signal amplification, which provide potential for the discrimination of low abundant target cells in liquid biopsy. [ABSTRACT FROM AUTHOR]

Dendritic growth is a major obstacle for the development of potassium metal anodes in K-ion batteries, which causes low coulombic efficiency, poor cycling stability and safety hazards. Herein, we report a 3D SnO2-coated conductive porous carbon nanofiber (PCNF) framework (PCNF@SnO2) as a host for K metal anodes. The SnO2 coating layer has a higher binding energy with K than with carbon and makes the PCNF framework highly potassiphilic, which regulates uniform K nucleation and deposition and suppresses dendritic growth. In addition, the interconnected 3D structure of the PCNF framework provides a large amount of void space and a robust structure to accommodate a large amount of K (87% @ 15 mg cm−2) and alleviate the stress/strain caused by volume expansion during plating/stripping. The PCNF@SnO2–K composite anode demonstrates an ultralong cycling stability of 1700 h at 1 mA cm−2, which is superior to those of other K metal anodes and even comparable with those of Li metal anodes reported in the literature. More importantly, enhanced performance is also achieved in a full cell using the composite K metal anode. Our results highlight a promising strategy for the development of stable and safe K metal anodes in KIBs. [ABSTRACT FROM AUTHOR]

Based on the unique property of preferential sequestration of guest molecules, coacervate microdroplets are proposed as enzyme active membrane-free protocells, in which uricase is loaded for efficient detoxification of uric acid in serum. [ABSTRACT FROM AUTHOR]

A near-infrared light triggered photothermal H2S-release platform was developed using a combination of photothermal nanoparticles and thermo-labile precursors, and was exploited for synchronous photothermal stimulation and gas release to suppress cell viability. Polyethyleneimine-dithiocarbamate as a H2S donor was assembled on reduced graphene oxide (rGO) nanosheets by electrostatic adsorption. In the nanocomposites, rGO nanosheets converted near-infrared light into thermal energy and activated the H2S donor to produce H2S. Synchronous photothermal stimulation and H2S gas release resulted in effective killing of cancer cells. This work presents an effective method that suppresses the growth of tumour cells and leads to an improved anti-cell proliferation outcome. Near-infrared light-triggered photothermal stimulation, in combination with H2S gas generation, may offer an effective strategy to further develop a cancer synergistic treatment platform. [ABSTRACT FROM AUTHOR]

Single-stranded DNA designed G-quadruplexes, modified with lipophilic 12-carbon spacers and cholesterol to span lipid membranes, were developed as smart transmembrane channels for selective and switchable potassium ion (K+) transport across membranes. [ABSTRACT FROM AUTHOR]

Aptamer-tailored DNA supersandwich assemblies are proposed as artificial receptors anchored onto a cell membrane, enabling catalase delivery with an 8-fold enhancement in efficiency. The catalase transfection led to inhibition of intracellular ROS, while the cell viability was also remarkably improved even when exposed to H2O2 and lipopolysaccharide environments. [ABSTRACT FROM AUTHOR]

The reactions of D2O with radical cations of guanine (9HGṖ+), 9-methylguanine (9MGṖ+), 2′-deoxyguanosine (dGuoṖ+) and guanosine (GuoṖ+) were studied in the gas phase, including measurements of reaction cross sections over a center-of-mass collision energy (Ecol) range from 0.1 to 2.0 eV and computation of reaction pathways at DLPNO-CCSD(T)/aug-cc-pVTZ//̉B97XD/6-31+G(d,p). Reaction efficiencies of all radical cations are well below unity (∼2% of collision rate), despite there being exoergic pathways. For each reactant ion, the energetically most favorable product channel corresponds to the formation of water complexes; however, this channel accounts for only 5% of the total cross section at the lowest Ecol and becomes negligible at high Ecol due to short complex lifetimes. The dominant product channel is H/D exchange that appears to be complex-mediated at low Ecol, but switches to a direct mechanism and accompanies keto–enol isomerization of the guanine moiety when Ecol increases. C8-hydroxylation, a minor yet the most biologically important channel, was observed for 9HGṖ+; and its mechanism was elucidated in the presence of single and double water molecules, of which the second water eliminates the barrier for C8-addition via a proton shuttle mechanism. All reactions show strong dependence on radical structures, with overall reactivity being 9HGṖ+> 9MGṖ+ ＞ dGuoṖ+≈ GuoṖ+. The reaction dynamics of 9HGṖ+ and 9MGṖ+ with water were simulated at Ecol = 0.1 eV using ̉B97XD/6-31+G(d), to reveal complex formation at the early stage of the reaction and the effects of N9-substitution. Trajectory results suggest that the lack of a W9 complex (water bonded to N9–H) is responsible for the reduced reactivity of N9-substituted radical cations; but the relatively long-lived W16 complexes (water bonded to N1–H and C6–O) of dGuoṖ+ and GuoṖ+ may enhance keto–enol isomerization. [ABSTRACT FROM AUTHOR]

A non-blocking split i-motif based aptamer anchoring strategy was developed as a general platform for sensing weakly acidic tumor microenvironment. By rationally tuning the response range to pH 7.0–6.4 and adjusting aptamer types, the strategy achieved specific, pHe-activated imaging of different cancers in vitro and in vivo. [ABSTRACT FROM AUTHOR]

Light-up aptamers have attracted growing attention due to their advantages of being label-free and having low fluorescence background. In this work, we developed a light-up fluorescence assay for label-free detection of tumor cells based on a bifunctional split aptamer (BFSA) that contained two DNA strands (BFSA-a and BFSA-b). BFSA-a and BFSA-b were constructed by combining aptamers ZY11 and ThT.2-2, which could specifically bind to the tumor cell SMMC-7721 and activate the fluorescence of thioflavin T (ThT). A Helper strand was introduced to hybridize with BFSA-b, and then BFSA-a and BFSA-b were separated if the target cell was absent. Only when the target cell is present can BFSA-a approach and hybridize with BFSA-b due to the ‘induced-fit effect’, which made the Helper strand dissociate. Then ThT bound to BFSA and the fluorescence of ThT was activated. The results indicated that this fluorescence assay had a good linear response to the target cells in the range of 250–20 000 cells in 100 μL binding buffer; the lowest cell number actually detected was 125 cells in 100 μL buffer. This assay also displayed excellent selectivity and was successfully applied to detect target cells in 20% human serum samples. The design of bifunctional split aptamers realized no-washing, label-free, low-cost, one-step detection of tumor cells, which could generate detectable fluorescence signals just by mixing nucleic acid aptamers and fluorescent reporter molecules with target cells. Such a design of aptamer probes also has the potential to construct stimuli-responsive controlled drug delivery systems. [ABSTRACT FROM AUTHOR]

Direct dynamics trajectories were calculated at the B3LYP/6-31G* level of theory to examine the intra-base pair proton transfer and dissociation of the deprotonated guanine (G)·cytosine (C) base pair under different excitation conditions, and to explore the origin of the nonstatistical product branching reported in a collision-induced dissociation (CID) experiment (Phys. Chem. Chem. Phys. 2016, 18, 32222). Trajectories for thermal excitation were initiated at two major conformers G·[C–H]− (hydrogen-bonded guanine and N1-deprotonated cytosine) and G·[C–H]−_PT (formed by proton transfer from the N1 of guanine to the N3 of deprotonated cytosine), and at their transition state (TS). Thermal excitation was realized by sampling molecular vibrational levels and TS's reaction coordinate energy with Boltzmann distributions at temperatures of 960 and 1330 K, which correspond to classical energies of 3.0 and 5.0 eV, respectively. Thermally excited trajectories undergo intra-base pair proton transfer extensively. The resulting conformation scrambling leads to nearly equal branching between the dissociation channels of [G–H]− + C and G + [C–H]−. Collisions of G·[C–H]− and G·[C–H]−_PT with Ar were each simulated at collision energies of 3.0 and 5.0 eV, respectively. The probability for intra-base pair proton transfer decreases substantially in collision trajectories. The CID product branching calculated on the basis of the population-weighted trajectory results of G·[C–H]− and G·[C–H]−_PT reveals a strong preference for [G–H]− + C, consistent with the experiment. Trajectory analysis corroborates that nonstatistical CID is attributed to inadequate conformation interconversion during collisional activation, and to the faster dissociation of the G·[C–H]−_PT conformer albeit G·[C–H]−_PT has nearly the same translational-to-vibrational energy transfer as G·[C–H]−. [ABSTRACT FROM AUTHOR]

A label-free and general thermo-controlled split apta-PCR strategy was first developed for the sensitive and specific detection of cancer cells. By integrating the temperature-responsive function of split aptamers with PCR amplification, a facile fluorescence assay of liver cancer SMMC-7721 cells was successfully realized with the detection of as low as 100 cells. [ABSTRACT FROM AUTHOR]

To combine cocktail chemotherapy and photodynamic therapy into one biocompatible and biodegradable nanocarrier, self-assembled DNA nanowires were fabricated and co-loaded with a photosensitizer chlorin e6 (Ce6) and a chemotherapeutic drug doxorubicin (DOX) for antitumor chemophotodynamic combination therapy. Two short DNA chains served as building blocks for the self-assembly of DNA nanowires in a supersandwich hybridization reaction that led to the successful formation of linear DNA nanowires of 500 bases, equal to a length of 167 nm. Ce6 and DOX were loaded onto the nanowires through covalent or noncovalent intercalation interactions, respectively. The DNA nanowires were taken up into cells, and the released Ce6 and DOX were ultimately distributed in different cellular compartments. The photosensitizer-loaded nanowires demonstrated increased generation of photodynamic reactive oxygen species (ROS) compared to that of free Ce6. In comparison with chemo- or photodynamic therapy alone, the combined treatment provided by DNA nanowires loaded with dual-drug significantly increased the incidence of HepG-2 cell death and produced a clear synergistic effect in the treatment of cancer cells. The DNA nanowire nanocarrier provided a flexible and quantitative drug-loading module that allowed for dose control of both drugs. More importantly, the DNA nanowires demonstrate a strong synergistic effect in antitumor chemophotodynamic combination therapy, likely because of increased photodynamic ROS generation and the distribution of Ce6 and DOX in different intracellular compartments. This work suggests that DNA nanowires may be useful as multifunctional and effective therapeutic nanocarriers for chemophotodynamic modalities in cancer therapy. [ABSTRACT FROM AUTHOR]

We report self-assembled nanocentipedes as multivalent vehicles for the delivery of immunostimulatory CpG ODNs. The multivalent vehicles could be internalized by RAW264.7 cells and stimulate the secretion of large amounts of cytokines, successively inducing effective apoptosis of cancer cells. [ABSTRACT FROM AUTHOR]

Herein, we proposed an enzyme-free strategy for the amplified detection of DNA by combining the efficient fluorescence enhancement capability of a β-cyclodextrin-tethered cationic polymer (cationic polyβ-CD) to pyrene with the amplification capability of target DNA triggered hybridization chain reaction (HCR). Cationic polyβ-CD with positive charge was synthesized. Two hairpin probes, H1 and H2, were employed in the system and the pyrene-labelled H2 was chosen as the signal unit. The pyrene attached on the sticky end of H2 was flexible and there was strong electrostatic interaction between cationic polyβ-CD and negatively-charged H2, so pyrene could easily enter the cavity of CD that is tethered on the cationic polymer, accompanied by significant fluorescence enhancement. Once target DNA was introduced, HCR was triggered to form a rigid long dsDNA polymer with pyrene attached on it. The pyrene was hardly able to enter the cavity of cationic polyβ-CD because of steric hindrance, leading to a weak fluorescent signal. Owing to the efficient pyrene fluorescence enhancement of cationic polyβ-CD and the amplified capability of HCR, an enzyme-free sensitive detection of target DNA was achieved with a detection limit of 0.1 nM and high selectivity. [ABSTRACT FROM AUTHOR]

We report a guided-ion beam mass spectrometric study on collision-induced dissociation (CID) of deprotonated guanine(G)·cytosine(C) base pairs and their 9-methylguanine (9MG) analogue with Xe, including measurements of product cross sections as a function of collision energy and determination of dissociation thresholds. DFT, RI-MP2 and DLPNO-CCSD(T) calculations and Rice–Ramsperger–Kassel–Marcus (RRKM) modeling were performed to elucidate structures and kinetics. The experiment and theoretical study have provided considerable insight into tautomerization, intra-base-pair proton transfer and dissociation of deprotonated G·C and 9MG·C. In contrast to the previously reported lowest-energy deprotonated base pair structure G·[C–H1]− that consists of H-bonded neutral guanine and N1-deprotonated cytosine, we found that proton transfer from guanine N1 to cytosine N3 within G·[C–H1]− (or 9MG·[C–H1]−) leads to another slightly more stable conformer denoted as G·[C–H1]−_PT1 (or 9MG·[C–H1]−_PT1). The conventional (non-proton-transferred) and the proton-transferred conformers are close in energy and interconvert quickly, but they can be distinguished by dissociation products. The conventional structure dissociates into deprotonated cytosine and neutral guanine, while the other dissociates into deprotonated guanine and neutral cytosine. The two dissociation asymptotes have similar threshold energies, but surprisingly the CID product mass spectra of deprotonated G·C and 9MG·C are both overwhelmingly dominated by deprotonated G or 9MG, with their branching ratios greater than RRKM predictions by one to two orders of magnitude. The proton-transferred structures of deprotonated base pairs and the “unexpected” non-statistical kinetics provide new leads for understanding purine–pyrimidine interactions, forming rare nucleobase tautomers, and base pair opening. [ABSTRACT FROM AUTHOR]

Nanoparticle fusion with cell membranes is an interesting phenomenon that may have crucial implications for their biomedical applications. Here, we proposed a biomimetic and controlled route to fusion of hydrophobic quantum dots (QDs) with the cell membranes of living cells, while preserving their sensing and optical properties and thus their capability of membrane imaging and single-nanoparticle tracking. Red blood cell (RBC) membrane lipids were extracted to phase transfer hydrophobic QDs and the resulting RBC-encapsulated QDs (RBC-QDs) can be well fused within cell membranes as membrane markers. The fusion was validated through single-nanoparticle imaging and different movement behaviours were reliably discriminated. RBC-QDs possessed some novel features, such as controllable selective membrane staining, no invasion, and high photobleaching resistance, which allowed for long-term imaging, and single-nanoparticle tracking. This approach provides a versatile platform for controlled hydrophobic QD-based fluorescence investigation of living cell membranes. [ABSTRACT FROM AUTHOR]

Mutagenicity of singlet O2 is due to its oxidatively generated damage to the guanine nucleobases of DNA. Oxidation of neutral guanosine has been assumed to be initiated by the formation of a transient 4,8-endoperoxide via a Diels–Alder cycloaddition of singlet O2. Protonation and deprotonation of guanosine represent another factor related to DNA damage and repair. Herein, 9-methylguanine was utilized as a model substrate to mimic the correlation between singlet O2 oxidation of the nucleoside and its ionization states, both in the absence and in the presence of water ligands. We used guided-ion-beam scattering tandem mass spectrometry to detect and quantify transient intermediates at room temperature. To provide a reliable description of reaction potential surfaces, different levels of theory including restricted and unrestricted density functional theory, CCSD(T), MP2, and multi-reference CASSCF and CASMP2 were applied. By means of molecular potential, kinetic and direct dynamics simulations, two reaction pathways were identified and neither follows the mechanism for neutral guanosine. Singlet O2 oxidation of protonated 9-methylguanine begins by a concerted cycloaddition; but it is mediated by a 5,8-endoperoxide. By contrast, a concerted cycloaddition does not occur for deprotonated 9-methylguanine. The latter involves a stepwise addition starting with the formation of an 8-peroxide, which subsequently evolves to a 4,8-endoperoxide. This dichotomy implies that acidic and basic media may lead to different chemistries for guanosine oxidation in aqueous solutions, starting from initial stage. The comparison with oxidation of protonated/deprotonated guanine illustrates the different mechanisms and products and particularly the suppressed oxidizability of 9-methylguanine vs. free guanine. [ABSTRACT FROM AUTHOR]

Nowadays, enzyme-free nucleic acid-based signal amplification strategies are frequently utilized in the design of biosensors due to their excellent sensitivity. Developing more extended analytical methods is fundamental for basic studies in the biological and biomedical fields. Herein, we introduce an enzyme-free amplified detection strategy for the small molecule adenosine. The approach is based on adenosine–aptamer binding triggered catalyzed hairpin assembly and host–guest interactions between β-cyclodextrin polymer (β-CDP) and pyrene. Two hairpin probes (probe H1 and probe H2) and an aptamer-trigger/inhibitor duplex probe were employed in the system and the pyrene-labeled probe H1 was chosen as the signal unit. In the absence of adenosine, the aptamer-trigger was inhibited by the inhibitor strand. The hairpin probes were in the closed hairpin formation without activation of the trigger strand. Pyrene labeled at the 5′-termini of the single-stranded stem of probe H1 could be easily trapped in the hydrophobic cavity of β-CDP because of weak steric hindrance, leading to a significant fluorescence enhancement. Once the hairpin assembly was catalyzed by the adenosine–aptamer binding event, a hybridized DNA duplex H1/H2 was created continuously. Pyrene labeled at the 5′-termini of the DNA duplex H1/H2 finds it difficult to enter the cavity of β-CDP due to steric hindrance, leading to a weaker fluorescence signal. Thus, the target could be detected by this simple mix-and-detect amplification method without a need for expensive and perishable protein enzymes. As low as 42 nM of adenosine was detected by this assay, which is comparable to that of some reported colorimetric methods. Meanwhile, the proposed method was further successfully applied to detect adenosine in human serum samples, showing great potential for adenosine detection from complex fluids. [ABSTRACT FROM AUTHOR]

Here we present a novel large Stokes shifting NIR fluorescent nanomicelle through the encapsulation of a quantum dot/methylene blue FRET pair, which is employed as an excellent contrast reagent for NIR fluorescence bioimaging. [ABSTRACT FROM AUTHOR]

A highly specific recognition-before-labeling strategy has been developed for sensitive detection of non-small cell lung cancer A549 cells, by using fluorescent QDs as signal units and DNA aptamers as recognition elements. A QD–aptamer system used for cell imaging and bioanalysis mostly relies on the recognition-after-labeling strategy in which aptamers were firstly labeled with QDs and then the QD–aptamer conjugates as a whole were utilized for specific recognition. Here in our strategy, aptamers were used firstly to recognize target cells, and then fluorescent QDs were sequentially added to bind the aptamers and light the target cells. The proposed recognition-before-labeling strategy didn't require the complex process of QD functionalization, and avoided the possible impact on the aptamer configuration from steric hindrance. Meanwhile, QDs, with strong fluorescence and good photostability, also give this method a high signal-to-background ratio (S/B). The recognition-before-labeling strategy is simple and sensitive, suggesting a new method for in vitro diagnostic assays of cancer cells. [ABSTRACT FROM AUTHOR]

A multiple amplification strategy has been developed for nucleic acid detection based on host–guest interaction between the β-cyclodextrin polymer (β-CDP) and pyrene. Briefly, the detection system consists of three parts: the polymerase and nicking enzyme-assisted isothermal strand displacement amplification (SDA) activated by a target DNA or microRNA; the exonuclease III-aided cyclic enzymatic amplification (CEA); and the fluorescence enhancement effect based on host–guest interaction between β-CDP and pyrene. This strategy showed a good positive linear correlation with target DNA concentrations in the range from 75 fM to 1 pM with a detection limit of 41 fM. Significantly, our amplification platform was further validated and evaluated successfully by assaying miRNA-21 in human serum. The proposed assay has great potential as a nucleic acid quantification method for use in biomedical research, clinical analysis and disease diagnostics. [ABSTRACT FROM AUTHOR]

A strategy for T4 polynucleotide kinase activity detection was proposed based on a β-cyclodextrin polymer (polyβ-CD) and an exonuclease reaction. The fluorescence of pyrene enhanced by more than 10 times in the presence of polyβ-CD, and a simple detection of T4 PNK was achieved with a detection limit of 0.02 units per mL. [ABSTRACT FROM AUTHOR]