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Small-molecule (SM) donor based ternary organic solar cells (OSCs) have drawn increasing attention owing to the remarkable photovoltaic performances achieved recently. In this study, a chlorinated benzodithiophene core and selenophene-containing π bridge based SM donor, namely CBTSeHR, was used as an SM donor guest to fabricate ternary OSCs owing to its favorable optoelectronic properties. CBTSeHR exhibits a good complementary absorption band and matched energy levels with the prevailing polymer donors and SM nonfullerene acceptors (NFAs), which is beneficial to light harvesting and charge transport. In addition, the incorporation of CBTSeHR could modulate the micro morphology and endow the ternary blend with more favorable phase separation size. Accordingly, the as cast ternary device prepared by introducing CBTSeHR into the D18:CH-6F host system exhibits an excellent power conversion efficiency (PCE) of 17.33%, which is even higher than that of the optimal binary host device (17.08%). After thermal annealing (TA) treatment, an outstanding PCE value of 18.41% with a high Voc of 0.901 V, FF of 0.767, and Jsc of 26.64 mA cm−2 was achieved, demonstrating the great success of SM donor based ternary OSCs. [ABSTRACT FROM AUTHOR]

Charge transfer complexes (CTCs) have become a promising and new class of photothermal conversion materials, in which the donor and acceptor can be regulated to control the energy gap, facilitating efficient absorption of near-infrared light. However, the successful co-crystallization of appropriate donor and acceptor pairs to form CTCs remains a challenging endeavor, as it requires addressing crucial issues including structural matching, co-assembly and crystallization conditions. Herein, on the basis of retaining the 'autonomy' of the assembly process, we leverage charge transfer and electron transfer processes of pyridinium building blocks to manipulate the photothermal behaviour in two distinct CTCs. Notably, CTC-1OH exhibits electron transfer initiated near-infrared photothermal conversion, while CTC-2OH has an intrinsic charge transfer-dependent photothermal effect with a photothermal efficiency as high as 35.4%. This work opens a new avenue for the development and optimization of the photothermal effect of CTCs. [ABSTRACT FROM AUTHOR]

Hydrogen sulfide (H2S) produced and metabolized by mitochondria is closely associated to human physiological function, but its mechanism is not fully revealed due to the difficulty in determining the dose of hydrogen sulfide. Therefore, fluorescent probes with both excellent mitochondrial targeting ability and rapid H2S detection are urgently needed. In this work, a novel fluorescent probe, TPAS-TN, was developed to detect H2S in mitochondria. TPAS-TN with a D–π–A structure had a large Stokes shift (213 nm), and possessed low background interference in cell imaging. By introducing a twisted triphenylamine group as the donor, TPAS-TN was endowed with AIE properties, and the positively charged pyridium unit was the acceptor, so that TPAS-TN exhibited good mitochondrial targeting ability and biocompatibility. Meanwhile, the π-bridge was composed of phenyl and dinitrophenyl (DNP) ether to make TPAS-TN exhibit "off–on" properties, low detection limit (69.5 nM), and high sensitivity and selectivity. Besides, TPAS-TN with the above characteristics was successfully applied to high-contrast H2S imaging in mitochondria. [ABSTRACT FROM AUTHOR]

The first catalytic asymmetric interrupted Attanasi reaction has been established. Under the catalysis of a bifunctional organocatalyst, the condensation of cyclic β-keto esters with azoalkenes readily occurred, delivering a variety of bicyclic fused 2,3-dihydropyrroles with vicinal quaternary stereogenic centers in good yields and with good to excellent enantioselectivities (27 examples, up to 96% yield and 95% ee). [ABSTRACT FROM AUTHOR]

A novel photocatalytic water splitting device was constructed using economic graphene quantum dots as a photocatalyst and a Ni-based complex [(tpy-CH＝N)2Ni]Cl2 (tpy = terpyridine) as a co-catalyst. Under visible light irradiation and with a bias of −0.1 V vs. NHE, it produced an extremely stable photocurrent density of −9 μA cm−2 for 3 h. [ABSTRACT FROM AUTHOR]

Herein, we have designed and synthesized a quinolinyl-AIE photosensitizer (TPE-4QL+) with an alternative elevated intersystem crossing (ISC) rate, which exhibits not only highly efficient photosensitivity but also high tumor cell specificity and an excellent mitochondrial targeting ability. In vitro experiments indicate that using TPE-4QL+ as a photosensitizer can induce a series of tumor cells to die with a low dose of radiation, but with no obvious toxicity to normal cells. The in vivo studies on a mouse model bearing a subcutaneous 4T1 xenograft also show that TPE-4QL+ can be used with high efficiency as a photosensitizer in PDT. [ABSTRACT FROM AUTHOR]

The search for laser-ignitable energetic materials catering to the safety and accuracy requirements in military and civilian affairs is an important yet challenging task. In this work, non-explosive and stable nitro bearing ligands of 3,5-dinitro-4-chlorobenzoic acid (HDNB-Cl) and 3,5-dinitro-4-hydroxybenzoic acid (HDNB-OH) have been adopted as energetic modules and organic building units to assemble with copper ions to construct energetic coordination complexes. The d–d transition introduced by Cu2+ endows the as-synthesized compounds to display remarkable absorptions of NIR light, and thus achieve efficient photothermal conversions upon irradiation by an 808 nm laser. As a result, the DNB-Cl based complexes can be laser-ignited and strong deflagration has been observed. The satisfactory thermal stability and tolerance toward friction and electrostatic discharge make them good candidates as laser-ignitable energetic materials. Unlike the conventional energetic materials based on nitrogen-rich organics (e.g., azido, furazan, and heterocyclic compounds), this work reveals that the easily functionalized nitro-bearing carboxylate ligand is an alternative energy module for assembling stable energetic complexes, and the coordination interaction-induced photothermal conversion would be an efficient strategy to achieve laser ignition for the resultant energetic compounds. [ABSTRACT FROM AUTHOR]

A robust metal-free catalytic strategy for the rapid construction of the valuable α-hydroxy-α-CF3-γ-ketoester skeleton with cheap and easily available stock chemicals (alkynes and trifluoropyruvate) as the starting material is described. This protocol shows very good functional group tolerance and is easily scaled up. Importantly, compared with transition metal-catalyzed methods, this strategy is made more environmentally friendly by employing a catalytic amount of H3PO4 as the catalyst. [ABSTRACT FROM AUTHOR]

A mass-tagged metal–organic framework (MOF) nanoprobe approach was developed for ultra-sensitive quantification of platelet protein CD44 by integrating activable aptamer recognition and MOF nanoprobe signal amplification with mass spectrometric detection. This approach offered high sensitivity and quantitative capability for low abundant protein analysis in tumor-educated platelets (TEPs), exhibiting great potential in cancer diagnosis and management. [ABSTRACT FROM AUTHOR]

Poly(ethylene glycol)-block-poly(L -lactide) (PEG–PLLA) is a biodegradable copolymer, which is widely applied to medicine and drug systems, and its morphology, organization and mechanical properties have been extensively investigated. However, the crystallization kinetics was not studied systemically with different block lengths, which is significant for the performance regulation and understanding of the crystallization behavior of block copolymers. In this study, PLLA, methoxy poly(ethylene glycol)-block-PLLA (MPEG-PLLA) diblock and PLLA–PEG–PLLA triblock copolymers with various molecular masses were melted and isothermally crystallized at different temperatures (Tc), and the crystallization kinetics of the PLLA and PLLA blocks was investigated using a differential scanning calorimeter (DSC). The results indicated that the crystallization kinetics of the PLLA block strongly relies on the architecture and block length. The crystallization rate first decreased and then increased with the increase in Tc for most of the specimens. The highest crystallization rate was found at 110 °C for all investigated PLLA samples. In the case of MPEG4-PLLA copolymers, the highest crystallization rate was observed at 100 °C. With the increase in the block length of PEG, the crystallization rate increased and the highest crystallization rate was found at lower a Tc value. High n values were found for block copolymers when crystallized at a relatively low temperature, which might be due to the dispersion of PEG in the interlamellar and interfibrillar regions of PLLA crystallites, and branched or dendritic structures developed upon subsequent crystallization. [ABSTRACT FROM AUTHOR]

Photoinduced bending behavior triggered by [2 + 2] cycloaddition of a photoactive complex has been successfully achieved, accompanied by photochromic and fluorescence changes that provide convenience for long-distance observation of photomechanical motion. The key design feature is based on the introduction of flexible methylene groups and cation–π interactions. Moreover, the potential application in photomechanical devices was reflected by bending and supporting force experiments on the complex composite film, which is of increasing importance especially in soft actuators and robots. [ABSTRACT FROM AUTHOR]

The development of peripheral nerve tissue engineering requires a safe and reliable methodology to construct biodegradable conduits. Herein, a new type of chitosan-based nerve-guide hydrogel conduit (CNHC) with enhanced mechanical flexibility in the wet state was fabricated using a one-step electrofabrication technology. The formation of the chitosan conduit is a physical process which can be conducted in a mild water phase without toxic crosslinks. The current density during electrofabrication has a profound effect on the physical and structural properties of the conduits. Cytocompatibility results indicate that the CNHC can promote cell proliferation and adhesion. Functional and histological tests indicate that the CNHC has the ability to guide the growth of axons through the conduit to reach a distal stump, which is closely similar to the autograft group. Overall, the results of this study demonstrate that the CNHCs from electrofabrication have a great potential in peripheral nerve regeneration. [ABSTRACT FROM AUTHOR]

It is a formidable challenge to understand water slippage through carbon nanotubes (CNTs), despite its great significance in fundamental research and technology. Herein, we propose an effective scheme to describe water slippage properties by extending two friction models – the phononic friction model and Einstein's diffusion model, both relying on the potential corrugation of water slippage. Our scheme effectively captures the tube-size effect on the viscosity and slippage of water molecules through CNTs. It also identifies the experimentally reported size-dependent transition from continuum to sub-continuum flow and further reveals that this transition is likely to be determined by the hydrogen bond instead of the structural transition or entropic change. Besides, the size-dependence of slip lengths is found to be controllable by temperature. Our methods are thus expected to be a useful basis for further studies on substance transport under confinement. [ABSTRACT FROM AUTHOR]

Liquid biopsy is becoming an innovative tool in precision oncology owing to its noninvasive identification of biomarkers circulating in the body fluid at various time points for continuous and real-time analysis of disease progression. MicroRNAs in blood exosomes are identified as a new promising class of potential biomarkers for cancer diagnostics and prognostics. Conventional detection of blood exosomal microRNAs need multiple-step, complicated, costly, and time-consuming sample preparation of exosomes isolation and RNA extract, which affect the accuracy and reproducibility of analytical results. In this work, we set up an in situ quantitative analysis of human plasma exosomal miR-1246 by a probe of 2′-O-methyl and phosphorothioate modified molecular beacon. The probe has outstanding nuclease resistance in highly active RNase A/T1/I, which makes it stable for direct application in blood samples. With rapid rupture of exosomes membrane by Triton X-100, the probe can enter exosomes to specifically target miR-1246 exhibiting quantitative fluorescent signals. Using the output signals as a diagnostic marker, we differentiated 33 breast cancer patients from 37 healthy controls with 97.30% sensitivity and 93.94% specificity at the best cutoff. The blood biopsy is simple without extracting plasma exosomes and their nucleic acids content, time-saving in about 2 h of total analysis process, and microvolumes needed for plasma sample, suggesting its good potential to clinical application. [ABSTRACT FROM AUTHOR]

The nonspecific toxicity of loaded drugs and the side effect of carriers are two obstacles that hinder the clinical development of anticancer nanodrugs. Herein, we developed a new nanodrug 3-(methylthio)-propanoate camptothecin (Pro-CPT) loaded with cross-linked (R)-(+)-lipoic acid nanoparticles (Pro-CPT@cLANs). The Pro-CPT is a pH-responsive prodrug of camptothecin (CPT) that can effectively reduce the systemic toxicity of CPT caused by premature release. The cLANs are nanoparticles with structural homology to (R)-(+)-lipoic acid (LA) that hold not only LA-like biocompatibility but also LA-like anticancer activity, which may further relieve the toxicity of loaded drugs by reducing their dosages through synergistic effects and precise drug release at the tumor sites. According to in vitro data, the IC Pro-CPT50 of Pro-CPT@cLANs against HT29 cells was 0.12 μM, ∼2.5 times lower than that of free Pro-CPT (0.3 μM); in vivo data showed that the tumor inhibition rate (TIR) and survival rate (SR) of Pro-CPT@cLANs against HT29 tumor-bearing nude mice were up to 85.1% and 80%, respectively, also far better than those of free CPT at the same dosage (TIR: 46%, SR: 0%). The Pro-CPT@cLANs provide a simple and efficient strategy to surmount the two obstacles in the development of nanodrugs and hold potential in clinical utility. [ABSTRACT FROM AUTHOR]

An eco-friendly and economical approach for the photocatalytic oxidation of organic inter-mediates by air under mild conditions is highly desirable in green and sustainable chemistry, where the photogeneration of active oxygen species plays a key role in improving conversion efficiency and selectivity. By using pyridinium derivatives as molecular mediators for electron transfer and energy transfer, the simultaneous activation of O2 from air into superoxide radicals and singlet oxygen species can be achieved, and a photoinduced electron transfer catalytic system for the oxidation of alcohols has been developed. Thus, we have successfully simplified the complicated catalytic system into a single molecular catalyst without any additional noble metals and co-catalysts/additives. The current photocatalytic system shows high catalytic efficiency not only for aromatic alcohols but also for aliphatic alcohols that are generally difficult to undergo aerobic oxidation at room temperature under air atmosphere, representing an ideal photocatalytic platform for green and economical organic syntheses. [ABSTRACT FROM AUTHOR]

The osmium(VI) nitrido complex [OsVI(N)(sap)(py)Cl] is a potential anti-cancer drug with promising in vitro antiproliferative activities toward a panel of cancer cell lines, including cisplatin-resistant cells (IC50 values of 2.8–13.8 μM). This drug targets DNA and changes its conformation via covalent binding and insertion. In vitro studies indicate that the drug induces HepG2 cells G2/M phase arrest, disrupts the mitochondrial membrane potential and causes caspase-mediated apoptosis. Further in vivo studies using HepG2-bearing nude mice reveal that this drug not only shows good antitumor efficacy of inhibiting tumor growth, but also does not show the side effect of weight loss. [ABSTRACT FROM AUTHOR]

Biological enzymes play important roles in mediating the biological reactions in vitro and in vivo due to their high catalytic activity, strong bioactivity, and high specificity; however, they have also some disadvantages such as high cost, low environmental stability, weak reusability, and difficult production. To overcome these shortcomings, functional nanomaterials including metallic nanoparticles, single atoms, metal oxides, alloys, and others have been utilized as nanozymes to mimic the properties and functions of natural enzymes. Due to the development of the synthesis and applications of two-dimensional (2D) materials, 2D nanomaterials have shown high potential to be used as novel nanozymes in biosensing, bioimaging, therapy, logic gates, and environmental remediation due to their unique physical, chemical, biological, and electronic properties. In this work, we summarize recent advances in the preparation and functionalization, as well as biosensor and immunoassay applications of various 2D material-based nanozymes. To achieve this aim, first we demonstrate the preparation strategies of 2D nanozymes such as chemical reduction, templated synthesis, chemical exfoliation, calcination, electrochemical deposition, hydrothermal synthesis, and many others. Meanwhile, the structure and properties of the 2D nanozymes prepared by conjugating 2D materials with nanoparticles, metal oxides, biomolecules, polymers, ions, and 2D heteromaterials are introduced and discussed in detail. Then, the applications of the prepared 2D nanozymes in colorimetric, electrochemical, fluorescent, and electrochemiluminescent sensors are demonstrated. [ABSTRACT FROM AUTHOR]

Optical techniques using developed laser and optical devices have made a profound impact on modern medicine, with "biomedical optics" becoming an emerging field. Sophisticated technologies have been developed in cancer nanomedicine, such as photothermal therapy and photodynamic therapy, among others. However, single-mode phototherapy cannot completely treat persistent tumors, with the challenges of relapse or metastasis remaining; therefore, combinatorial strategies are being developed. In this review, the role of light in cancer therapy and the challenges of phototherapy are discussed. The development of combinatorial strategies with other therapeutic methods, including chemotherapy, immunotherapy, gene therapy, and radiotherapy, is presented and future directions are further discussed. This review aims to highlight the significance of light in cancer therapy and discuss the combinatorial strategies that show promise in addressing the challenges of phototherapy. [ABSTRACT FROM AUTHOR]

Enantioselective fluorescent sensors show large potential for fast, real-time, and highly sensitive measurement of the concentration and enantiomeric composition of chiral molecules. Among all of the sensors, BINOL-based sensors have been actively investigated and extensively used to carry out highly enantioselective, sensitive recognition of chiral α-hydroxycarboxylic acids, amino acids, amino acid derivatives, amino alcohols and amines. In this manuscript, the recent progress of chiral BINOL-based sensors for enantioselective fluorescence recognition of different substrates is reviewed and discussed. The structure of BINOL is tuned by introducing various groups or molecules which systematically changed its fluorescence properties and offered potential for rapid assays of chiral organic molecules. From the development of this area, we gain fresh insight into the challenges and chances of BINOL-based sensors. [ABSTRACT FROM AUTHOR]

The discovery of layered two-dimensional (2D) ferroelectric materials has promoted the development of miniaturized and highly integrated ferroelectric electronics. The 2D ferroelectric materials can be applied in a radiation environment, in which the effect of radiation on these materials should be considered. However, the effects of radiation on 2D ferroelectric materials may be entirely different from those on traditional ferroelectric materials. Ionization effect-induced domain switching can be recovered by applying an external electric field, whereas the displacement effect initiated by radiation particles produces crystal structure damage. The displacement damage that is extremely difficult to recover may have a negative impact on the application of 2D ferroelectric materials in a radiation environment. In this study, the effect of displacement induced by neutron irradiation on the promising α-In2Se3 nanoflakes was investigated. Neutron irradiation (1 MeV) with a fluence of 1014 cm−2 was used for avoiding ionization effects in a certain range. Although the topography of α-In2Se3 does not change underneutron irradiation, vacancies have been proved to be induced by neutron irradiation; furthermore, it has been identified that the vacancies mostly originate from the loss of In atoms. The out-of-plane (OOP) and in-plane (IP) domain structures of the α-In2Se3 nanoflakes with a few layers only slighlty change. In addition, the polarization of the irradiated nanoflakes could still be reversed. All these findings show that although the vacancies may influence the band structure and polarizaiton values of α-In2Se3, the ferroelectric performance may have a strong resistance to neutron irradiation. Therefore, our investigation implies that α-In2Se3 is an excellent 2D ferroelectric material for application in radiation-resistant electronic devices in the future. [ABSTRACT FROM AUTHOR]

In this study, we report a facile one-pot chemical etching approach to simply and rapidly prepare gold nanoclusters capped with luminol (Lum-AuNCs) in an alkaline aqueous solution at room temperature. A series of characterization studies have been carried out to explore the morphology, the optical properties and chemical components of Lum-AuNCs. The average diameter of Lum-AuNCs is 1.8 ± 0.3 nm, exhibiting fluorescence near 510 nm upon excitation at 420 nm with a quantum yield of 14.29% and an average fluorescence lifetime of 9.47 ns. On the basis of the ligand-induced etching of glutathione (GSH) to the intermediate (luminol capped gold nanoparticles, abbreviated as Lum-AuNPs), a novel and simple method for the fluorescence determination of GSH has been established. The method displays a good linear response in the range of 0.05–300 μM toward GSH with a limit of detection of 35 nM. This detection strategy with high sensitivity and selectivity facilitates its practical application for the detection of GSH levels in cell extracts. The in vitro cell results illustrate that Lum-AuNCs have good cytocompatibility and can be used to readily differentiate normal cells and tumor cells. [ABSTRACT FROM AUTHOR]

Multi-drug resistant bacterial infection has become one of the most serious threats to global public health. The preparation and application of new antibacterial materials are of great significance for solving the infection problem of bacteria, especially multi-drug resistant bacteria. The exceptional antibacterial effects of metal nanoparticles based on their unique physical and chemical properties make such systems ideal for application as antibacterial drug carriers or self-modified therapeutic agents both in vitro and in vivo. Metal nanoparticles also have admirable clinical application prospects due to their broad antibacterial spectrum, various antibacterial mechanisms and excellent biocompatibility. Nevertheless, the in vivo structural stability, long-term safety and cytotoxicity of the surface modification of metal nanoparticles have yet to be further explored and improved in subsequent studies. Herein, we summarized the research progress concerning the mechanism of metal nanomaterials in terms of antibacterial activity together with the preparation of metal nanostructures. Based on these observations, we also give a brief discussion on the current problems and future developments of metal nanoparticles for antibacterial applications. [ABSTRACT FROM AUTHOR]

Silicon has received much attention due to its high theoretical capacity as the electrode of lithium-ion batteries (LIBs). However, the poor stability caused by the volume expansion problem affects the cycle life of batteries, thus severely limiting the application of the silicon anode. In the present work, we engineered silicon nanotubes with hollow-structure to accommodate the volume expansion of silicon and improve the electrochemical stability of lithium ion batteries. Hollow silicon nanotubes were in situ synthesized on carbon cloth (HSiNTs/CC) by reducing silicon oxide and corroding zinc oxide nanorod templates and directly used as the anode of lithium-ion batteries without any binders or conductive additives. The results of electrochemical measurements indicated that HSiNTs/CC exhibits superior LIB performance with excellent cycling stability and good rate capability. At a current density of 100 mA g−1, a reversible capacity of 1420 mA h g−1 was achieved and the fabricated LIB could retain 93.7% of the initial capacity after 100 cycles. Even at a decoupled current density of 1000 mA g−1, the LIB still possesses a capacity of 1026 mA h g−1 and 98.3% capacity retention after 100 cycles. The results demonstrated that the thin hollow structures were well suited to accommodate the volume expansion of silicon and improve the stability of the HSiNTs/CC anode during the lithiation–delithiation cycles, which shines some light on the reasonable design and preparation of silicon anodes for ultra-stable lithium-ion batteries. [ABSTRACT FROM AUTHOR]

One major challenge in current brain research is generating an integrative understanding of the brain's functions and disorders from its multiscale neuronal architectures and connectivity. Thus, innovative neurotechnology tools are urgently required for deciphering the multiscale functional and structural organizations of the brain at hierarchical scales from the molecular to the organismal level by multiple brain research initiatives launched by the European Union, United States, Australia, Canada, China, Korea, and Japan. To meet this demand, microfluidic chips (μFCs) have rapidly evolved as a trans-scale neurotechnological toolset to enable multiscale studies of the brain due to their unique advantages in flexible microstructure design, multifunctional integration, accurate microenvironment control, and capacity for automatic sample processing. Here, we review the recent progress in applying innovative μFC-based neuro-technologies to promote multiscale brain research and uniquely focus on representative applications of μFCs to address challenges in brain research at each hierarchical level. We discuss the current trend of combinational applications of μFCs with other neuro- and biotechnologies, including optogenetics, brain organoids, and 3D bioprinting, for better multiscale brain research. In addition, we offer our insights into the existing outstanding questions at each hierarchical level of brain research that could potentially be addressed by advancing microfluidic techniques. This review will serve as a timely guide for bioengineers and neuroscientists to develop and apply μFC-based neuro-technologies for promoting basic and translational brain research. [ABSTRACT FROM AUTHOR]

A dual-photoresponsive coordination polymer displaying color-distinguishable olefin/cyclobutane-linked pyridinium radical states through photoinduced electron transfer and photocycloaddition has been successfully assembled based on the monoquaternized trans-1,2-bis(4-pyridyl)ethylene and electron-rich benzenetetra-carboxylate anion. The synergy of charge-transfer and cation–π interactions within the framework endows the compound with excellent stability toward high temperature (350 °C), acidic/basic environments (pH = 2–12) and organic solvents. Reversible recovery from the radical states to their initial states, and reverse-cyclization can be achieved upon heat-treatment. [ABSTRACT FROM AUTHOR]

The cross-linked small-molecule micelles (cSMs) have found applications in many fields but their low loading capacity and non-fluorescence property hindered their further development. Herein, water-soluble organic nanoparticles were applied as templates to "stretch" the hydrophobic core of cSMs and photo-cross-linking was employed to supply photoluminescence. The resulting cross-linked small-molecule capsules (cSCs) not only reserve the superior properties of cSMs of accurate monomer, easy functionalization and robust stability, but also achieve high drug loading capacity and excitation wavelength-dependent fluorescence, where the drug loading contents (DLCs) for various hydrophobic drugs were more than 30-fold higher than that of cSMs, and the maximum quantum yield could be as high as 12.0%. Featuring these superiorities, the cSCs hold promising potential in many fields and an example of doxorubicin-loaded cSCs (DOX@cSCs) for multichannel imaging-guided drug delivery is shown in this work. [ABSTRACT FROM AUTHOR]

Compared with normal cells, cancer or tumor cells have a specific microenvironment and apparently possess a relatively large amount of ROS/RNS, and their overexpression is one of the important reasons for tumor development and deterioration. Therefore, monitoring the changes of intracellular ROS/RNS can improve the awareness of the clinical manifestations of the disease, which will be beneficial for the early diagnosis of cancer and improving treatment efficiency. Herein, in this study we have exploited and constructed a novel strategy based on the SiC@C nanowire electrode for intracellular electrochemical analysis to monitor ROS levels in cancer or tumor cells. Firstly, the SiC@C nanowire electrode was utilized to detect the intracellular ROS radical changes involved in the relevant biological processes of cancer cells where fluorescent zinc nanoclusters were biosynthesized in situ in target cancer cells by using the intracellular microenvironment and specificity of these cancer cells. By combining a confocal fluorescence microscopy study simultaneously, our observations illustrate that accompanied by the apparent change of the intracellular ROS, these in situ biosynthesized fluorescent nanoclusters gradually accumulate inside the cytosolic area with the increase of the reaction time. Moreover, it is evident that the size of the SiC@C nanoelectrodes can match the single cell dimensions, and its unique high spatial resolution provides the possibility of relevant intracellular molecular detection. These nanoelectrochemical biosensors can be adopted to quantitatively determine the change of the ROS content in target single cells in the relevant biological microenvironment or during the in situ biosynthesis process, and are also beneficial for understanding the related mechanism of some specific biological processes including the in situ synthesis at the single cell level. [ABSTRACT FROM AUTHOR]

Histone post-translational modification (PTM) is a marker for gene transcription and is involved in a range of cancers, such as breast cancer. Most importantly, different modifications of a specific site (e.g., mono-, di- and tri-methylations and acetylation at a lysine residue) are individually enriched in particular regions of the genome, indicating that they may serve distinct functions. How these patterns are built and whether downstream events are dependent on the precise site-specific modification status are still poorly understood. One of the prerequisites is to obtain quantitative information on individual modification forms. Currently, the low abundance of these forms creates a great challenge. In this study, a targeted proteomics assay based on liquid chromatography-tandem mass spectrometry (LC-MS/MS) coupled with single template oriented molecularly imprinted polymers (MIPs) was developed to attempt to simultaneously quantify site-specific histone mono-, di- and tri-methylated and acetylated forms. Surrogate peptides, including an unmodified one, were selected as targets in both MIP enrichment and subsequent LC-MS/MS detection. As a consequence, a limit of quantification (LOQ) of ∼0.5 nM was achieved, which was 10-fold more sensitive than without MIPs and much more sensitive than mass spectrometry involving a scanning mode. Finally, the assay was employed to quantitatively analyze the H3K79, H3K122 and H4K31 modification status in human breast cell lines. [ABSTRACT FROM AUTHOR]

Multidrug resistance (MDR) is one of the major obstacles for tumor therapy. Intake by receptor-mediated endocytosis enables molecules to bypass ABC transporter efflux, which is the primary mechanism of MDR. Here, we developed a novel pH/enzyme dual-responsive polypeptide prodrug to reverse multidrug resistance. This drug is composed of pH/MMP2-sensitive nanoparticles (MSNPs) self-assembled from mPEG–peptide–DOX. MSNPs can overcome sequential physiological barriers of multidrug resistance by prolonging the circulation time through PEGylation, enhancing tumor accumulation through passive targeting, increasing tumor penetration by enzyme-sensitive PEG deshielding, bypassing ABC transporter efflux by undergoing receptor-mediated endocytosis, and inducing sufficient DOX release from nanoparticles triggered by lysosomal pH. The reversal of MDR by MSNPs was evaluated in MCF-7/ADR cells and nude mice bearing tumors consisting of MCF-7/ADR cells. Both in vitro and in vivo studies showed that the MSNPs can effectively reverse MDR. Thus, MSNPs may constitute a potentially promising strategy for overcoming MDR in clinical applications. [ABSTRACT FROM AUTHOR]

Optimal integration between the polyethylene terephthalate (PET) graft and host bone is a prerequisite to obtain a satisfactory outcome after graft implantation for ligament reconstruction. Recent studies indicate that complex biosignals including immunoregulation, cell recruitment, and osteogenic differentiation provided by the extracellular matrix (ECM) are conducive to promoting osseointegration. In the present study, a chondroitin sulfate (CS)/polydopamine-modified PET graft was developed to regulate the local immune microenvironment, guide stem cell behavior, and promote new bone formation. We found that CS-modified PET grafts significantly regulated the macrophage phenotype switching from M1 to M2 and promoted the expression of pro-repair cytokines including interleukin (IL)-4, IL-10 and transforming growth factor (TGF)-β1. Moreover, the immunoregulatory function of CS-modified PET guided stem cell behaviors, including recruitment, adhesion, and proliferation, and enhanced the osteogenic differentiation of stem cells. In vivo experiments confirmed that CS-modified PET switched the local immune microenvironment status from pro-inflammatory to anti-inflammatory, up-regulated osteogenic marker expression, and promoted the bone regeneration process, so as to achieve graft-bone osseointegration. These results indicate that an ECM-biomimetic immunoregulatory coating is an effective approach to promote graft integration. This study proposes an effective strategy for an artificial graft to achieve graft-bone osseointegration through immunoregulatory osteogenesis. [ABSTRACT FROM AUTHOR]

Liposomes have been applied extensively as nanocarriers in the clinic (e.g., to deliver anticancer drugs) due to their biocompatibility and internal cavity structures. However, their low drug-loading capacity (DLC; <10%) and uncontrolled release reduce their efficacy in cancer treatment. To improve the DLC and monitor release of drugs in cells in real-time, stimuli-responsive vesicles must be developed. We present various amphiphilic tetraphenylethylene (TPE)-containing compounds designed to self-assemble into liposome-like vesicles that can load both hydrophilic and hydrophobic drugs. The highest DLC for doxorubicin (DOX) was ≤26% for vesicles (diameter = 105 nm) that could encapsulate hydrophilic DOX in the interior water pool and hydrophobic DOX via π–π stacking interactions between DOX and the TPE moiety. The stable vesicles could respond rapidly to overexpressed glutathione in the tumor microenvironment to release loaded DOX for cancer therapy. Vesicles modified by active targeting groups showed more efficacious tumor treatment compared with unmodified vesicles and free DOX in vitro and in vivo. Simultaneously we observed, spatiotemporally, the subcellular location of the delivery system and release process of DOX. Our work provides a novel nano-engineering technology to integrate the desired properties for anticancer theranostics: high DLC, stability, stimuli-responsiveness to the cancer environment, drug-delivery monitoring, active targeting, and suppression of tumor growth. These novel vesicles could be employed as multifunctional drug-delivery systems for cancer therapy. [ABSTRACT FROM AUTHOR]