Surface Modification of Solid‐State Nanopores for Sticky‐Free Translocation of Single‐Stranded DNA

Nanopore technology is one of the most promising approaches for fast and low‐cost DNA sequencing application. Single‐stranded DNA detection is primary objective in such device, while solid‐state nanopores remain less explored than their biological counterparts due to bio‐molecule clogging issue caused by surface interaction between DNA and nanopore wall. By surface coating a layer of polyethylene glycol (PEG), solid‐state nanopore can achieve long lifetime for single‐stranded DNA sticky‐free translocation at pH 11.5. Associated with elimination of non‐specific binding of molecule, PEG coated nanopore presents new surface characteristic as less hydrophility, lower 1/f noise, and passivated surface charge responsiveness on pH. Meanwhile, conductance blockage of single‐stranded DNA is found to be deeper than double‐stranded DNA, which can be well described by a string of blobs model for a quasi‐equilibrium state polymer in constraint space.     

An Impedimetric‐Fluorescence Double‐Checking Biosensor with Enhanced Reliability Based on Graphene Oxide

MicroRNA (miRNA) is a class of clinically significant diagnostic and prognostic markers for some diseases, especially for cancer. Graphene oxide (GO) has been reported to bind and quench dye‐labeled single‐stranded DNA (ssDNA) probes while it has less affinity toward double‐stranded DNA (dsDNA) or hybrids of DNA/RNA. This property makes it very suitable to construct a double‐checking system for miRNA detection, thus increasing the reliability of detection. This kind of double‐checking sensor will have great potential in clinical diagnosis. Based on this concept, in this study a simple and sensitive electrochemical impedance spectroscopy biosensor for miRNA‐21 is developed using a GO‐coated electrode. Simultaneously, the fluorescence of the remaining hybridization solution which contains dissociated duplex of ssDNA/miRNA is also investigated to double check the signal and increase its reliability. Therefore, a GO‐based double‐checking biosensor is developed for miRNA‐21 detection, which shows simplicity, high sensitivity and selectivity, and outstanding reliability. This is the first time to integrate the electrochemical impedimetric method and fluorescence method in one sensing system for detecting miRNA based on GO. It is believed that this work will have a profound impact on the design of graphene‐based biosensors for miRNA detection.     

High Efficiency Organic Solar Cells Achieved by the Simultaneous Plasmon‐Optical and Plasmon‐Electrical Effects from Plasmonic Asymmetric Modes of Gold Nanostars

The plasmon‐optical effects have been utilized to optically enhance active layer absorption in organic solar cells (OSCs). The exploited plasmonic resonances of metal nanomaterials are typically from the fundamental dipole/high‐order modes with narrow spectral widths for regional OSC absorption improvement. The conventional broadband absorption enhancement (using plasmonic effects) needs linear‐superposition of plasmonic resonances. In this work, through strategic incorporation of gold nanostars (Au NSs) in between hole transport layer (HTL) and active layer, the excited plasmonic asymmetric modes offer a new approach toward broadband enhancement. Remarkably, the improvement is explained by energy transfer of plasmonic asymmetric modes of Au NS. In more detail, after incorporation of Au NSs, the optical power in electron transport layer transfers to active layer for improving OSC absorption, which otherwise will become dissipation or leakage as the role of carrier transport layer is not for photon‐absorption induced carrier generation. Moreover, Au NSs simultaneously deliver plasmon‐electrical effects which shorten transport path length of the typically low‐mobility holes and lengthen that of high‐mobility electrons for better balanced carrier collection. Meanwhile, the resistance of HTL is reduced by Au NSs. Consequently, power conversion efficiency of 10.5% has been achieved through cooperatively plasmon‐optical and plasmon‐electrical effects of Au NSs.     

Solution‐Processed Wide‐Bandgap Organic Semiconductor Nanostructures Arrays for Nonvolatile Organic Field‐Effect Transistor Memory

In this paper, the development of organic field‐effect transistor (OFET) memory device based on isolated and ordered nanostructures (NSs) arrays of wide‐bandgap (WBG) small‐molecule organic semiconductor material [2‐(9‐(4‐(octyloxy)phenyl)‐9H‐fluoren‐2‐yl)thiophene]3 (WG₃) is reported. The WG₃ NSs are prepared from phase separation by spin‐coating blend solutions of WG₃/trimethylolpropane (TMP), and then introduced as charge storage elements for nonvolatile OFET memory devices. Compared to the OFET memory device with smooth WG₃ film, the device based on WG₃ NSs arrays exhibits significant improvements in memory performance including larger memory window (≈45 V), faster switching speed (≈1 s), stable retention capability (>10⁴ s), and reliable switching properties. A quantitative study of the WG₃ NSs morphology reveals that enhanced memory performance is attributed to the improved charge trapping/charge‐exciton annihilation efficiency induced by increased contact area between the WG₃ NSs and pentacene layer. This versatile solution‐processing approach to preparing WG₃ NSs arrays as charge trapping sites allows for fabrication of high‐performance nonvolatile OFET memory devices, which could be applicable to a wide range of WBG organic semiconductor materials.     

Wet/Sono‐Chemical Synthesis of Enzymatic Two‐Dimensional MnO2 Nanosheets for Synergistic Catalysis‐Enhanced Phototheranostics

2D nanomaterials have attracted broad interest in the field of biomedicine owing to their large surface area, high drug‐loading capacity, and excellent photothermal conversion. However, few studies report their “enzyme‐like” catalytic performance because it is difficult to prepare enzymatic nanosheets with small size and ultrathin thickness by current synthetic protocols. Herein, a novel one‐step wet‐chemical method is first proposed for protein‐directed synthesis of 2D MnO₂ nanosheets (M‐NSs), in which the size and thickness can be easily adjusted by the protein dosage. Then, a unique sono‐chemical approach is introduced for surface functionalization of the M‐NSs with high dispersity/stability as well as metal‐cation‐chelating capacity, which can not only chelate ⁶⁴Cu radionuclides for positron emission tomography (PET) imaging, but also capture the potentially released Mn²⁺ for enhanced biosafety. Interestingly, the resulting M‐NS exhibits excellent enzyme‐like activity to catalyze the oxidation of glucose, which represents an alternative paradigm of acute glucose oxidase for starving cancer cells and sensitizing them to thermal ablation. Featured with outstanding phototheranostic performance, the well‐designed M‐NS can achieve effective photoacoustic‐imaging‐guided synergistic starvation‐enhanced photothermal therapy. This study is expected to establish a new enzymatic phototheranostic paradigm based on small‐sized and ultrathin M‐NSs, which will broaden the application of 2D nanomaterials.     

Cross‐Talk Between Ionic and Nanoribbon Current Signals in Graphene Nanoribbon‐Nanopore Sensors for Single‐Molecule Detection

Nanopores are now being used not only as an ionic current sensor but also as a means to localize molecules near alternative sensors with higher sensitivity and/or selectivity. One example is a solid‐state nanopore embedded in a graphene nanoribbon (GNR) transistor. Such a device possesses the high conductivity needed for higher bandwidth measurements and, because of its single‐atomic‐layer thickness, can improve the spatial resolution of the measurement. Here measurements of ionic current through the nanopore are shown during double‐stranded DNA (dsDNA) translocation, along with the simultaneous response of the neighboring GNR due to changes in the surrounding electric potential. Cross‐talk originating from capacitive coupling between the two measurement channels is observed, resulting in a transient response in the GNR during DNA translocation; however, a modulation in device conductivity is not observed via an electric‐field‐effect response during DNA translocation. A field‐effect response would scale with GNR source–drain voltage (V_ds), whereas the capacitive coupling does not scale with V_ds. In order to take advantage of the high bandwidth potential of such sensors, the field‐effect response must be enhanced. Potential field calculations are presented to outline a phase diagram for detection within the device parameter space, charting a roadmap for future optimization of such devices.     

Two‐Dimensional Antimonene‐Based Photonic Nanomedicine for Cancer Theranostics

Antimonene (AM) is a recently described two‐dimensional (2D) elemental layered material. In this study, a novel photonic drug‐delivery platform based on 2D PEGylated AM nanosheets (NSs) is developed. The platform's multiple advantages include: i) excellent photothermal properties, ii) high drug‐loading capacity, iii) spatiotemporally controlled drug release triggered by near‐infrared (NIR) light and moderate acidic pH, iv) superior accumulation at tumor sites, v) deep tumor penetration by both extrinsic stimuli (i.e., NIR light) and intrinsic stimuli (i.e., pH), vi) excellent multimodal‐imaging properties, and vii) significant inhibition of tumor growth with no observable side effects and potential degradability, thus addressing several key limitations of cancer nanomedicines. The intracellular fate of the prepared NSs is also revealed for the first time, providing deep insights that improve cellular‐level understanding of the nano–bio interactions of AM‐based NSs and other emerging 2D nanomaterials. To the best of knowledge, this is the first report on 2D AM‐based photonic drug‐delivery platforms, possibly marking an exciting jumping‐off point for research into the application of 2D AM nanomaterials in cancer theranostics.     

Polymer Nanosheet Containing Star‐Like Copolymers: A Novel Scalable Controlled Release System

Poly(ε‐caprolactone) (PCL)‐based nanomaterials, such as nanoparticles and liposomes, have exhibited great potential as controlled release systems, but the difficulties in large‐scale fabrication limit their practical applications. Among the various methods being developed to fabricate polymer nanosheets (PNSs) for different applications, such as Langmuir–Blodgett technique and layer‐by‐layer assembly, are very effort consuming, and only a few PNSs can be obtained. In this paper, poly(ε‐caprolactone)‐based PNSs with adjustable thickness are obtained in large quantity by simple water exposure of multilayer polymer films, which are fabricated via a layer multiplying coextrusion method. The PNS is also demonstrated as a novel controlled guest release system, in which release kinetics are adjustable by the nanosheet thickness, pH values of the media, and the presence of protecting layers. Theoretical simulations, including Korsmeyer–Peppas model and Finite‐element analysis, are also employed to discern the observed guest‐release mechanisms.     

Programmable NIR‐II Photothermal‐Enhanced Starvation‐Primed Chemodynamic Therapy using Glucose Oxidase‐Functionalized Ancient Pigment Nanosheets

Chemodynamic therapy (CDT) has attracted considerable attention recently, but the poor reaction kinetics restrict its practical utility in clinic. Herein, glucose oxidase (GOx) functionalized ancient pigment nanosheets (SrCuSi₄O₁₀, SC) for programmable near‐infrared II (NIR‐II) photothermal‐enhanced starvation primed CDT is developed. The SC nanosheets (SC NSs) are readily exfoliated from SC bulk suspension in water and subsequently functionalized with GOx to form the nanocatalyst (denoted as SC@G NSs). Upon laser irradiation, the photothermal effect of SC NSs can enhance the catalytic activity of GOx for NIR‐II photothermal‐enhanced starvation therapy, which effectively eliminates intratumoral glucose and produces abundant hydrogen peroxide (H₂O₂). Importantly, the high photothermal‐conversion efficiency (46.3%) of SC@G NSs in second biological window permits photothermal therapy of deep‐seated tumors under the guidance of NIR‐II photoacoustic imaging. Moreover, the acidity amplification due to gluconic acid generation will in turn accelerate the degradation of SC NSs, facilitating the release of strontium (Sr) and copper (Cu) ions. Both the elevated H₂O₂ and the released ions will prime the Cu²⁺/Sr²⁺‐H₂O₂ reaction for enhanced CDT. Thus, a programmable NIR‐II photothermal‐enhanced starvation primed CDT is established to combat cancer with minimal side effects.     

A Novel Top‐Down Synthesis of Ultrathin 2D Boron Nanosheets for Multimodal Imaging‐Guided Cancer Therapy

Single atom nonmetal 2D nanomaterials have shown considerable potential in cancer nanomedicines, owing to their intriguing properties and biocompatibility. Herein, ultrathin boron nanosheets (B NSs) are prepared through a novel top‐down approach by coupling thermal oxidation etching and liquid exfoliation technologies, with controlled nanoscale thickness. Based on the PEGylated B NSs, a new photonic drug delivery platform is developed, which exhibits multiple promising features for cancer therapy and imaging, including: i) efficient NIR‐light‐to‐heat conversion with a high photothermal conversion efficiency of 42.5%, ii) high drug‐loading capacity and triggered drug release by NIR light and moderate acidic pH, iii) strong accumulation at tumor sites, iv) multimodal imaging properties (photoacoustic, photothermal, and fluorescence imaging), and v) complete tumor ablation and excellent biocompatibility. As far as it is known, this is the first report on the top‐down fabrication of ultrathin 2D B NSs by the combined thermal oxidation etching and liquid exfoliation, as well as their application as a multimodal imaging‐guided drug delivery platform. The newly prepared B NSs are also expected to provide a robust and useful 2D nanoplatform for various biomedical applications.     

H2S‐Scavenged and Activated Iron Oxide‐Hydroxide Nanospindles for MRI‐Guided Photothermal Therapy and Ferroptosis in Colon Cancer

Overproduced hydrogen sulfide (H₂S) is of vital importance for the progress of colon cancer and promotes cancer cellular proliferation. Devising pharmacological nanomaterials for tumor‐specific H₂S activation will be significant for precise colon cancer treatment. Herein, a biocompatible fusiform iron oxide‐hydroxide nanospindles (FeOOH NSs) nanosystem for magnetic resonance imaging (MRI), ferroptosis, and H₂S based cascade reaction‐enhanced combinational colon cancer treatment is developed. The FeOOH NSs can effectively scavenge endogenous H₂S via the reduction reaction to prohibit the growth of CT26 colon cancer. The cascade produced FeS driven by overexpressed H₂S exhibits near‐infrared‐triggered photothermal therapy capability and Fe²⁺‐mediated ferroptosis functionality. Meanwhile, the as‐prepared FeOOH NSs can light up tumor tissues as a potent MRI contrast agent. Additionally, FeOOH NSs present desirable biosafety in a murine model for up to three months and avoid any long‐term toxicity. Furthermore, it is found that these H₂S‐responsible nanotheranostics do not cause any cure effects on other cancer types, such as 4T1 breast cancer. Overall, the findings illustrate that the biocompatible FeOOH NSs can be successfully employed as a theranostic for specifically treating colon cancer, which may promote the clinical translation and development of H₂S‐responsive nanoplatforms.     

In Situ Growth of Pd Nanosheets on g‐C3N4 Nanosheets with Well‐Contacted Interface and Enhanced Catalytic Performance for 4‐Nitrophenol Reduction

Loading novel metal nanosheets onto nanosheet support can improve their catalytic performance, but the morphological incompatibility makes it difficult to construct a well‐contacted interface, which is of particular interest in supported catalysts. Herein, Pd nanosheets (Pd NSs) are supported onto graphitic carbon nitride nanosheets (CNNSs) with intimate face‐to‐face contact through an in situ growth method. This method overcomes the limitations of the morphological incompatibility and ensures the intimate interfacial contact between Pd NSs and CNNSs. The nitrogen‐rich nature of CNNSs endows Pd NSs with abundant anchoring sites, which optimizes the electronic structure and improves the chemical and morphological stability of Pd NSs. The supported Pd NSs demonstrate high dispersion and exhibit largely enhanced activity toward the reduction of 4‐nitrophenol. The concentration‐normalized rate constant is up to 3052 min^?1 g^?1 L, which is 5.4 times higher than that obtained by unsupported Pd NSs. No obvious deactivation is observed after six runs of the recycling experiments. It is believed that the supported novel metal nanosheets with the intimately contacted interface may show promising applications in catalysis.     

Automated Fabrication of 2‐nm Solid‐State Nanopores for Nucleic Acid Analysis

We demonstrate the automated and reproducible fabrication of sub‐2‐nm nanopores in 10‐nm thick silicon nitride membranes, through controlled dielectric breakdown in solution. Our results reveal that under the appropriate conditions, nanopores can be fabricated with a size no larger than 2.0 ± 0.5‐nm in diameter for a sample of N = 23 nanopores, with an average and standard deviation of 1.3 ± 0.6‐nm. The dimensions of these nanopores are confirmed by using individual translocating DNA molecules as molecular rulers. We show that a 2.0‐nm and a 2.1‐nm diameter nanopore are capable of distinguishing single‐stranded DNA versus double‐stranded DNA, and that a 2.4‐nm diameter nanopore can be used to investigate the overstretching transition in short dsDNA fragments. These results highlight the reliability and precision of the automated fabrication of nanopores via controlled dielectric breakdown, showing great promise for the manufacturing of future nanopore‐based technologies.     

Generalized Synthesis of Ultrathin Cobalt‐Based Nanosheets from Metallophthalocyanine‐Modulated Self‐Assemblies for Complementary Water Electrolysis

The development of effective approaches for preparing large‐area, self‐standing, ultrathin metal‐based nanosheets, which have proved to be favorable for catalytic applications such as water electrolysis, is highly desirable but remains a great challenge. Reported herein is a simple and versatile strategy to synthesize ultrathin Co₃O₄ and CoP NSs consisting of close‐packed nanoparticles by pyrolyzing cobalt(II) phthalocyanine/graphene oxide (CoPc/GO) assemblies in air and subsequent topotactic phosphidation while preserving the graphene‐like morphology. The strong π–π stacking interactions between CoPc and GO, and the inhibiting effect of the tetrapyrrole‐derived macrocycle for grain growth during the catalytic carbon gasification contribute to the NSs forming. The resulting homologous Co₃O₄ and CoP NSs display outstanding catalytic activity in alkaline media toward the oxygen evolution reaction and the hydrogen evolution reaction, respectively, ascribed to the richly exposed active sites, and the expedited electrolyte/ion transmission path. The integrated asymmetrical two‐electrode configuration also presents a superior cell voltage of 1.63 V at 10 mA cm^?2 for overall water splitting, accompanied with the excellent durability during long‐term cycling. Further evidences validate that this strategy is appropriate to fabricate graphene‐like ultrathin NSs of many other metal oxides, such as Fe₂O₃, NiO, MoO₃, and mixed‐metal oxides, for various applications.     

DNA‐Modification of Eukaryotic Cells

A novel bioorthogonal method for the modification of cells with single‐stranded DNA oligomers is compared to five alternative methods with respect to labeling efficacy, specificity, and effects on cell viability. The new method is based on oxime ligation of aminooxybiotin to aldehyde groups installed by periodate cleavage of cell‐surface glycans, followed by the coupling of preformed DNA–streptavidin conjugates. As compared with two literature‐reported methods based on direct coupling of N‐hydroxysuccinimidyl (NHS)–DNA or NHS–biotinylation as well as with techniques based on strain‐promoted alkyne‐azide cycloaddition, this method shows the highest labeling densities and is sufficiently mild to avoid cell damage. Functionality of the DNA tags is demonstrated by DNA‐directed immobilization on solid substrates and assembly of small cell aggregates.     

Recent Advances in Synthesis and Biomedical Applications of Two‐Dimensional Transition Metal Dichalcogenide Nanosheets

During recent decades, a giant leap in the development of nanotechnology has been witnessed. Numerous nanomaterials with different dimensions and unprecedented features have been developed and provided unimaginably wide scope to solve the challenging problems in biomedicine, such as cancer diagnosis and therapy. Recently, two‐dimensional (2D) transition metal dichalcogenide (TMDC) nanosheets (NSs), including MoS₂, WS₂, and etc., have emerged as novel inorganic graphene analogues and attracted tremendous attention due to their unique structures and distinctive properties, and opened up great opportunities for biomedical applications, including ultrasensitive biosensing, biological imaging, drug delivery, cancer therapy, and antibacterial treatment. A comprehensive overview of different synthetic methods of ultrathin 2D TMDC NSs and their state‐of‐the‐art biomedical applications, especially those that have appeared in the past few years, is presented. At the end of this review, the future opportunities and challenges for 2D TMDC NSs in biomedicine are also discussed.     

Aqueous Phase Exfoliating Quasi‐2D CsPbBr3 Nanosheets with Ultrahigh Intrinsic Water Stability

All‐inorganic cesium lead halide perovskite nanocrystals (NCs) have emerged as attractive optoelectronic materials due to the excellent optical and electronic properties. However, their environmental stability, especially in the presence of water, is still a significant challenge for their further commercialization. Here, ultrahigh intrinsically water‐stable all‐inorganic quasi‐2D CsPbBr₃ nanosheets (NSs) via aqueous phase exfoliation method are reported. Compared to conventional perovskite NCs, these unique quasi‐2D CsPbBr₃ nanosheets present an outstanding long‐term water stability with 87% photoluminescence (PL) intensity remaining after 168 h under water conditions. Moreover, the photoluminescence quantum yields (PLQY) of quasi‐2D CsPbBr₃ NSs is up to 82.3%, and these quasi‐2D CsPbBr₃ NSs also present good photostability of keeping 85% PL intensity after 2 h under 365 nm UV light. Evidently, such quasi‐2D perovskite NSs will open up a new way to investigate the intrinsic stability of all‐inorganic perovskites and further promote the commercial development of perovskite‐based optoelectronic and photovoltaic devices.     

A Droplet‐Based High‐Throughput SERS Platform on a Droplet‐Guiding‐Track‐Engraved Superhydrophobic Substrate

A novel droplet‐based surface‐enhanced Raman scattering (SERS) sensor for high‐throughput real‐time SERS monitoring is presented. The developed sensors are based on a droplet‐guiding‐track‐engraved superhydrophobic substrate covered with hierarchical SERS‐active Ag dendrites. The droplet‐guiding track with a droplet stopper is designed to manipulate the movement of a droplet on the superhydrophobic substrate. The superhydrophobic Ag dendritic substrates are fabricated through a galvanic displacement reaction and subsequent self‐assembled monolayer coating. The optimal galvanic reaction time to fabricate a SERS‐active Ag dendritic substrate for effective SERS detection is determined, with the optimized substrate exhibiting an enhancement factor of 6.3 × 10⁵. The height of the droplet stopper is optimized to control droplet motion, including moving and stopping. Based on the manipulation of individual droplets, the optimized droplet‐based real‐time SERS sensor shows high resistance to surface contaminants, and droplets containing rhodamine 6G, Nile blue A, and malachite green are successively controlled and detected without spectral interference. This noble droplet‐based SERS sensor reduces sample preparation time to a few seconds and increased detection rate to 0.5 µ L s^?1 through the simple operation mechanism of the sensor. Accordingly, our sensor enables high‐throughput real‐time molecular detection of various target analytes for real‐time chemical and biological monitoring.     

Virus‐Templated Plasmonic Nanoclusters with Icosahedral Symmetry via Directed Self‐Assembly

The assembly of plasmonic nanoparticles with precise spatial and orientational order may lead to structures with new electromagnetic properties at optical frequencies. The directed self‐assembly method presented controls the interparticle‐spacing and symmetry of the resulting nanometer‐sized elements in solution. The self‐assembly of three‐dimensional (3D), icosahedral plasmonic nanosclusters (NCs) with resonances at visible wavelengths is demonstrated experimentally. The ideal NCs consist of twelve gold (Au) nanospheres (NSs) attached to thiol groups at predefined locations on the surface of a genetically engineered cowpea mosaic virus with icosahedral symmetry. In situ dynamic light scattering (DLS) measurements confirm the NSs assembly on the virus. Transmission electron micrographs (TEM) demonstrate the ability of the self‐assembly method to control the nanoscopic symmetry of the bound NSs, which reflects the icosahedral symmetry of the virus. Both, TEM and DLS show that the NCs comprise of a distribution of capsids mostly covered (i.e., 6–12 NS/capsid) with NSs. 3D finite‐element simulations of aqueous suspensions of NCs reproduce the experimental bulk absorbance measurements and major features of the spectra. Simulations results show that the fully assembled NCs give rise to a 10‐fold surface‐averaged enhancement of the local electromagnetic field.     

Smart Drug Delivery Nanocarriers with Self‐Assembled DNA Nanostructures

Self‐assembled DNA nanostructures have emerged as a type of nano‐biomaterials with precise structures, versatile functions and numerous applications. One particularly promising application of these DNA nanostructures is to develop universal nanocarriers for smart and targeted drug delivery. DNA is the genetic material in nature, and inherently biocompatible. Nevertheless, cell membranes are barely permeable to naked DNA molecules, either single‐ or double‐ stranded; transport across the cell membrane is only possible with the assistance of transfection agents. Interestingly, recent studies revealed that many DNA nanostructures could readily go into cells with high cell uptake efficiency. In this Progress Report, we will review recent advances on using various DNA nanostructures, e.g., DNA nanotubes, DNA tetrahedra, and DNA origami nanorobot, as drug delivery nanocarriers, and demonstrate several examples aiming at therapeutic applications with CpG‐based immunostimulatory and siRNA‐based gene silencing oligonucleotides.