DNA‐Driven Two‐Layer Core–Satellite Gold Nanostructures for Ultrasensitive MicroRNA Detection in Living Cells

It is a significant challenge to achieve controllable self‐assembly of superstructures for biological applications in living cells. Here, a two‐layer core–satellite assembly is driven by a Y‐DNA, which is designed with three nucleotide chains that hybridized through complementary sequences. The two‐layer core–satellite nanostructure (C₃₀S₅S₁₀ NS) is constructed using 30 nm gold nanoparticles (Au NPs) as the core, 5 nm Au NPs as the first satellite layer, and 10 nm Au NPs as the second satellite layer, resulting in a very strong circular dichroism (CD) and surface‐enhanced Raman scattering. After optimization, the yield is up to 85%, and produces a g‐factor of 0.16 × 10^?2. The hybridization of the target microRNA (miRNA) with the molecular probe causes a significant drop in the CD and Raman signals, and this phenomenon is used to detect the miRNA in living cells. The CD signal has a good linear range of 0.011–20.94 amol ng_RNA^?1 and a limit of detection (LOD) of 0.0051 amol ng_RNA^?1, while Raman signal with the range of 0.052–34.98 amol ng_RNA^?1 and an LOD of 2.81 × 10^?2 amol ng_RNA^?1. This innovative dual‐signal method can be used to quantify biomolecules in living cells, opening the way for ultrasensitive, highly accurate, and reliable diagnoses of clinical diseases.     

Lighting Up MicroRNA in Living Cells by the Disassembly of Lock‐Like DNA‐Programmed UCNPs‐AuNPs through the Target Cycling Amplification Strategy

Intracellular microRNAs imaging based on upconversion nanoprobes has great potential in cancer diagnostics and treatments. However, the relatively low detection sensitivity limits their application. Herein, a lock‐like DNA (LLD) generated by a hairpin DNA (H1) hybridizing with a bolt DNA (bDNA) sequence is designed, which is used to program upconversion nanoparticles (UCNPs, NaYF₄@NaYF₄:Yb, Er@NaYF₄) and gold nanoparticles (AuNPs). The upconversion emission is quenched through luminescence resonance energy transfer (LRET). The multiple LLD can be repeatedly opened by one copy of target microRNA under the aid of fuel hairpin DNA strands (H2) to trigger disassembly of AuNPs from the UCNP, resulting in the lighting up of UCNPs with a high detection signal gain. This strategy is verified using microRNA‐21 as model. The expression level of microRNA‐21 in various cells lines can be sensitively measured in vitro, meanwhile cancer cells and normal cells can be easily and accurately distinguished by intracellular microRNA‐21 imaging via the nanoprobes. The detection limit is about 1000 times lower than that of the previously reported upconversion nanoprobes without signal amplification. This is the first time a nonenzymatic signal amplification method has been combined with UCNPs for imaging intracellular microRNAs, which has great potential for cancer diagnosis.     

Multiplexed Molecular Imaging of Fresh Tissue Surfaces Enabled by Convection‐Enhanced Topical Staining with SERS‐Coded Nanoparticles

There is a need for intraoperative imaging technologies to guide breast‐conserving surgeries and to reduce the high rates of re‐excision for patients in which residual tumor is found at the surgical margins during postoperative pathology analyses. Feasibility studies have shown that utilizing topically applied surface‐enhanced Raman scattering (SERS) nanoparticles (NPs), in conjunction with the ratiometric imaging of targeted versus untargeted NPs, enables the rapid visualization of multiple cell‐surface biomarkers of cancer that are overexpressed at the surfaces of freshly excised breast tissues. In order to reliably and rapidly perform multiplexed Raman‐encoded molecular imaging of large numbers of biomarkers (with five or more NP flavors), an enhanced staining method has been developed in which tissue surfaces are cyclically dipped into an NP‐staining solution and subjected to high‐frequency mechanical vibration. This dipping and mechanical vibration (DMV) method promotes the convection of the SERS NPs at fresh tissue surfaces, which accelerates their binding to their respective biomarker targets. By utilizing a custom‐developed device for automated DMV staining, this study demonstrates the ability to simultaneously image four cell‐surface biomarkers of cancer at the surfaces of fresh human breast tissues with a mixture of five flavors of SERS NPs (four targeted and one untargeted control) topically applied for 5 min and imaged at a spatial resolution of 0.5 mm and a raster‐scanned imaging rate of >5 cm² min^?1.     

Cancer Cell Membrane Camouflaged Nanoprobe for Catalytic Ratiometric Photoacoustic Imaging of MicroRNA in Living Mice

Herein, a cancer cell (MCF‐7 cell) membrane‐encapsulated dendritic mesoporous silica nanoparticle simultaneously functionalized with DNA‐photoacoustic (DNA‐PA) probes and glutathione (GSH)‐responsive DNA fuel strands for PA imaging of tumor‐related miRNA in living mice with signal amplification ability is developed. It is demonstrated that one target miRNA can trigger disassembly of multiple PA fluorophore probes from the quencher with the aid of GSH‐responsive DNA fuel strands via the entropy‐driven process, resulting remarkable amplified change of PA signal ratio. Using oncogenic miRNA‐21 as a model, a linear relationship between miRNA‐21 concentrations and PA ratio in a dynamic range from 10 × 10^?12 m to 100 × 10^?9 m and a limit of detection down to 11.69 × 10^?12 m are established. The accurate PA signal observation related to miRNA‐21s in the tumor area in living mice is demonstrated, and the PA signal ratio increases significantly via the injection of miRNA‐21. It is anticipated that the catalytic ratiometric PA imaging system can be applied to an array of molecular detection in living system by rational detection probe design.     

Engineering Gyroid‐Structured Functional Materials via Templates Discovered in Nature and in the Lab

In search of optimal structures for functional materials fabrication, the gyroid (G) structure has emerged as a promising subject of widespread research due to its distinct symmetry, 3D interconnected networks, and inherent chiral helices. In the past two decades, researchers have made great progress fabricating G‐structured functional materials (GSFMs) based on G templates discovered both in nature and in the lab. The GSFMs demonstrate extraordinary resonance when interacting with light and matter. The superior properties of GSFMs can be divided into two categories based on the dominant structural properties, namely, dramatic optical performances dominated by short‐range symmetry and well‐defined texture, and effective matter transport due to long‐range 3D interconnections and high integrity. In this review, G templates suitable for fabrication of GSFMs are summarized and classified. State‐of‐the‐art optical applications of GSFMs, including photonic bandgap materials, chiral devices, plasmonic materials, and matamaterials, are systematically discussed. Applications of GSFMs involved in effective electron transport and mass transport, including electronic devices, ultrafiltration, and catalysis, are highlighted. Existing challenges that may hinder the final application of GSFMS together with possible solutions are also presented.     

On‐Electrode Synthesis of Shape‐Controlled Hierarchical Flower‐Like Gold Nanostructures for Efficient Interfacial DNA Assembly and Sensitive Electrochemical Sensing of MicroRNA

The performance for biomolecular detection is closely associated with the interfacial structure of a biosensor, which profoundly affects both thermodynamics and kinetics of the assembly, binding and signal transduction of biomolecules. Herein, it is reported on a one‐step and template‐free on‐electrode synthesis method for making shape‐controlled gold nanostructures on indium tin oxide substrates, which provide an electrochemical sensing platform for ultrasensitive detection of nucleic acids. Thus‐prepared hierarchical flower‐like gold nanostructures (HFGNs) possess large surface area that can readily accommodate the assembly of DNA probes for subsequent hybridization detection. It is found that the sensitivity for electrochemical DNA sensing is critically dependent on the morphology of HFGNs. By using this new strategy, a highly sensitive electrochemical biosensor is developed for label‐free detection of microRNA‐21 (miRNA‐21), a biomarker for lung cancers. Importantly, it is demonstrated that this biosensor can be employed to measure the miRNA‐21 expression level from human lung cancer cell (A549) lysates and worked well in 100% serum, suggesting its potential for applications in clinical diagnosis and a wide range of bioanalysis.     

Target‐Triggered Assembly of Nanogap Antennas to Enhance the Fluorescence of Single Molecules and Their Application in MicroRNA Detection

Nanogap antennas are plasmonic nanostructures with a strong electromagnetic field generated at the gap region of two neighboring particles owing to the coupling of the collective surface plasmon resonance. They have great potential for improving the optical properties of fluorophores. Herein, nanogap antennas are constructed using an aqueous solution‐based method to overcome the defects of weak fluorescence and photobleaching associated with traditional organic dyes, and a highly sensitive nanogap antenna‐based sensing strategy is presented for the detection of low‐abundance nucleic acid biomarkers via a target‐triggered strand displacement amplification (SDA) reaction between two DNA hairpins that are tagged to the tips of gold nanorods (Au NRs). In the presence of targets, end‐to‐end Au NR dimers gradually form, and the fluorophores quenched by the Au NRs exhibit a dramatic fluorescence enhancement due to the plasmon‐enhanced fluorescence effect of nanogap antennas. Meanwhile, the SDA reaction results in secondary amplification of fluorescence signals. Combined with single‐molecule counting, this method applied in miRNA‐21 detection can achieve a low detection limit of 97.2 × 10^?18 m . Moreover, accurate discrimination between different cells through miRNA‐21 imaging demonstrates the potential of this method in monitoring the expression level of low‐abundance nucleic acid biomarkers.     

Sensitive and Stable Tin–Lead Hybrid Perovskite Photodetectors Enabled by Double‐Sided Surface Passivation for Infrared Upconversion Detection

Tin(Sn)‐based perovskite is currently considered one of the most promising materials due to extending the absorption spectrum and reducing the use of lead (Pb). However, Sn²⁺ is easily oxidized to Sn⁴⁺ in atmosphere, causing more defects and degradation of perovskite materials. Herein, double‐sided interface engineering is proposed, that is, Sn‐Pb perovskite films are sandwiched between the phenethylammonium iodide (PEAI) in both the bottom and top sides. The larger organic cations of PEA+ are arranged into a perovskite surface lattice to form a 2D capping layer, which can effectively prevent the water and oxygen to destroy bulk perovskite. Meanwhile, the PEA+ can also passivate defects of iodide anions at the bottom of perovskite films, which is always present but rarely considered previously. Compared to one sided passivation, Sn‐Pb hybrid perovskite photodetectors contribute a significant enhancement of performance and stability, yielding a broadband response of 300–1050 nm, a low dark current density of 1.25 × 10^–3 mA cm^–2 at –0.1 V, fast response speed of 35 ns, and stability beyond 240 h. Furthermore, the Sn‐Pb broadband photodetectors are integrated in an infrared up‐conversion system, converting near‐infrared light into visible light. It is believed that a double‐sided passivation method can provide new strategies to achieving high‐performance perovskite photodetectors.     

Ultrabroadband Metasurface for Efficient Light Trapping and Localization: A Universal Surface‐Enhanced Raman Spectroscopy Substrate for “All” Excitation Wavelengths

Most reported surface‐enhanced Raman spectroscopy (SERS) substrates can work for individual excitation wavelengths only. Therefore, different substrates have to be used for different excitation wavelengths, which consumes more biological/chemical materials, substrates, and measurement time. Here, an ultrabroadband super absorbing metasurface that can work as a universal substrate for low cost and high performance SERS sensing is reported. Due to broadband light trapping and localized field enhancement, this structure can work for almost “all” available laser lines from 450 to 1100 nm. This predicted feature is validated by SERS experiment using five different excitation laser lines, obtaining a high enhancement factor of 5.3 × 10⁷ and very good uniformity over large areas.     

A Targeted and FRET‐Based Ratiometric Fluorescent Nanoprobe for Imaging Mitochondrial Hydrogen Peroxide in Living Cells

Hydrogen peroxide (H₂O₂) is a prominent member of the reactive oxygen species family and plays crucial roles in living organisms, thus detecting H₂O₂ and elucidating its biological functions has become an important area of biological and biomedical research. Herein, a multifunctional fluorescent nanoprobe is demonstrated for detecting mitochondrial H₂O₂. The nanoprobe is prepared by covalently linking a mitochondria‐targeting ligand (triphenylphosphonium, TPP) and a H₂O₂ recognition element (PFl) onto carbon dots (CDs). For this nanoprobe, the CD serves as the carrier and the FRET donor. In the presence of H₂O₂, the PFl moieties on a CD undergo structural and spectral conversion, affording the nanoplatform a FRET‐based ratiometric probe for H₂O₂. The nanoprobe displays excellent water dispersibility, high sensitivity and selectivity, satisfactory cell permeability, and very low cytotoxicity. Following the living cell uptake, this nanoprobe can specifically target and stain the mitochondria; and it can detect the exogenous H₂O₂ in L929 cells, as well as the endogenously produced mitochondrial H₂O₂ in Raw 264.7 cells upon stimulation by PMA. This study shows that CDs can serve as promising nano‐carriers for fabricating practical multifunctional fluorescent nanosensors.     

Spatiotemporally Controllable Peptide‐Based Nanoassembly in Single Living Cells for a Biological Self‐Portrait

Simultaneous precise localization and activity evaluation of a biomolecule in a single living cell is through an enzyme‐specific signal‐amplification process, which involves the localized, site‐specific self‐assembly, and activation of a presignaling molecule. The inactive presignaling tetraphenylethylene (TPE)‐peptide derivative, TPE‐YpYY, is nondetectable and highly biocompatible and these small molecules rapidly diffuse into living cells. Upon safely arriving at an active site, and accessing the catalytic pocket of an enzyme, TPE‐YpYY immediately and quantitatively accumulates in situ in response to enzymatic activity, forms an enzyme anchor TPE‐YYY nanoassembly, displays aggregation‐induced emission behavior, and finally lights up the active enzyme, indicating its activity, and allowing its status in living cells to be tracked. This simple and direct self‐portrait method can be used to monitor dynamic self‐assembly processes in individual living cells and may provide new insights that reveal undiscovered biological processes and that aid in developing biomedical hybrid devices. In the future, this strategy of molecular design can be further expanded to the noninvasive investigation of other bioactive molecules, thus facilitating quantitative imaging.