A Sensitive Aptasensor Based on a Hemin/G‐Quadruplex‐Assisted Signal Amplification Strategy for Electrochemical Detection of Gastric Cancer Exosomes

Emerging evidence indicates that exosomes derived from gastric cancer cells enhance tumor migration and invasion through the modulation of the tumor microenvironment. However, it remains a major problem to detect cancer‐specific exosomes due to technical and biological challenges. Most of the methods reported could not achieve efficient detection of tumor‐derived exosomes in the background of normal exosomes. Herein, a label‐free electrochemical aptasensor is presented for specific detection of gastric cancer exosomes. This platform contains an anti‐CD63 antibody modified gold electrode and a gastric cancer exosome specific aptamer. The aptamer is linked to a primer sequence that is complementary to a G‐quadruplex circular template. The presence of target exosomes could trigger rolling circle amplification and produce multiple G‐quadruplex units. This horseradish peroxidase mimicking DNAzyme could catalyze the reduction of H₂O₂ and generate electrochemical signals. This aptasensor exhibits high selectivity and sensitivity toward gastric cancer exosomes with a detection limit of 9.54 × 10² mL^?1 and a linear response range from 4.8 × 10³ to 4.8 × 10⁶ exosomes per milliliter. Therefore, this electrochemical aptasensor is expected to become a useful tool for the early diagnosis of gastric cancer.     

A GSH‐Gated DNA Nanodevice for Tumor‐Specific Signal Amplification of microRNA and MR Imaging–Guided Theranostics

Developing tumor‐responsive diagnosis and therapy strategies for tumor theranostics is still a challenge owing to their high accuracy and specificity. Herein, an AND logic gated–DNA nanodevice, based on the fluorescence nucleic acid probe and polymer‐modified MnO₂ nanosheets, for glutathione (GSH)‐gated miRNA‐21 signal amplification and GSH‐activated magnetic resonance (MR) imaging–guided chemodynamic therapy (CDT) is reported. In the presence of overexpressed miRNA and GSH (tumor cells), the nanodevice can be in situ activated and release significantly amplified fluorescence signals and MR signals. Conversely, the fluorescence signal is quenched and MR signal remains at the background level with low miRNA and GSH (normal cells), efficiently reducing the false‐positive signals by more than 50%. Under the guide of miRNA profiling and MR imaging, the tumor‐responsive hydroxyl radical ( · OH) can effectively kill tumor cells. Furthermore, the nanodevice shows catalase‐like activity and glucose oxidase–like activity with the performance of O₂ production and glucose consumption. This is the first time to fabricate a tumor‐responsive theranostic DNA nanodevice with tumor‐specific signal amplification of microRNA and GSH‐activated MR imaging for CDT, potential hypoxia relief and starvation therapy, which provides a new insight for designing smart theranostic strategies.     

Ultrasensitive Detection of Prostate‐Specific Antigen and Thrombin Based on Gold‐Upconversion Nanoparticle Assembled Pyramids

Self‐assembled nanostructures have been used for the detection of numerous cancer biomarkers. In this study, a gold‐upconversion‐nanoparticle (Au‐UCNP) pyramid based on aptamers is fabricated to simultaneously detect thrombin and prostate‐specific antigen (PSA) using surface‐enhanced Raman scattering (SERS) and fluorescence, respectively. The higher the concentration of thrombin, the lower the intensity of SERS. PSA connected with the PSA aptamer leads to an increase in fluorescence intensity. The limit of detection of thrombin and PSA reaches 57 × 10^?18 and 0.032 × 10^?18m , respectively. In addition, the pyramid also exhibits great target specificity. The results of human serum target detection demonstrate that the Au‐UCNP pyramid is an excellent choice for the quantitative determination of cancer biomarkers, and is feasible for the early diagnosis of cancer.     

Controlled Vectorial Electron Transfer and Photoelectrochemical Applications of Layered Relay/Photosensitizer‐Imprinted Au Nanoparticle Architectures on Electrodes

Two configurations of molecularly imprinted bis‐aniline‐bridged Au nanoparticles (NPs) for the specific binding of the electron acceptor N,N′‐dimethyl‐4,4′‐bipyridinium (MV²⁺) and for the photosensitizer Zn(II)‐protoporphyrin IX (Zn(II)‐PP‐IX) are assembled on electrodes, and the photoelectrochemical features of the two configurations are discussed. Configuration I includes the MV²⁺‐imprinted Au NPs matrix as a base layer, on which the Zn(II)‐PP‐IX‐imprinted Au NPs layer is deposited, while configuration II consists of a bilayer corresponding to the reversed imprinting order. Irradiation of the two electrodes in the presence of a benzoquinone/benzohydroquinone redox probe yields photocurrents of unique features: (i) Whereas configuration I yields an anodic photocurrent, the photocurrent generated by configuration II is cathodic. (ii) The photocurrents obtained upon irradiation of the imprinted electrodes are substantially higher as compared to the nonimprinted surfaces. The high photocurrents generated by the imprinted Au NPs‐modified electrodes are attributed to the effective loading of the imprinted matrices with the MV²⁺ and Zn(II)‐PP‐IX units and to the effective charge separation proceeding in the systems. The directional anodic/cathodic photocurrents are rationalized in terms of vectorial electron transfer processes dictated by the imprinting order and by the redox potentials of the photosensitizer/electron acceptor units associated with the imprinted sites in the two configurations.     

Highly Sensitive and Selective Field‐Effect‐Transistor NonEnzyme Dopamine Sensors Based on Pt/Conducting Polymer Hybrid Nanoparticles

Dopamine (DA), as one of catecholamine family of neurotransmitters, is crucially important in humans owing to various critical effects on biometric system such as brine circuitry, neuronal plasticity, organization of stress responses, and control of cardiovascular and renal organizations. Abnormal level of dopamine in the central nervous system causes several neurological diseases, e.g., schizophrenia, Parkinson's disease, and attention deficit hybperactivity disorder (ADHD)/attention deficit disorder (ADD). In this report, we suggest the fabrication of nonenzyme field effect transistor (FET) sensor composed of immobilized Pt particle decorated conducting‐polymer (3‐carboxylate polypyrrole) nanoparticles (Pt_CPPy) to detect dopamine. The hybrid nanoparticles (NPs) are produced by means of facile chemical reduction of pristine CPPyNP‐contained Pt precursor (PtCl₄) solution. The Pt_CPPys are then immobilized on an amine‐functionalized (–NH₂) interdigitated‐array electrode substrate, through the formation of covalent bonds with amine groups (–CONH). The resulting Pt_CPPy‐based FET sensors exhibit high sensitivity and selectivity toward DA at unprecedentedly low concentrations (100 × 10^?15m ) and among interfering biomolecules, respectively. Additionally, due to the covalent bonding involved in the immobilization process, a longer lifetime is expected for the FET sensor.     

Electrospray Encapsulation of Hydrophilic and Hydrophobic Drugs in Poly(L‐lactic acid) Nanoparticles

An electrospray method is developed for preparation of beclomethasone‐dipropionate‐ and salbutamol‐sulfate‐loaded biodegradable poly(L ‐lactic acid) nanoparticles. Different set‐up parameters for electrospraying are examined on particle size, and preparation conditions are optimized for producing spherical‐drug‐loaded nanoscale particles by controllable processing parameters. Polylactide (PLA)–drug nanoparticles with average diameters of around 200 nm are achieved in a stable cone‐jet mode with a flow rate of 4 µL min^?1, polymer concentration of 1%, and ammonium hydroxide content of 0.05%. Morphology and size of the drug–polymer nanoparticles are analyzed by scanning electron microscopy and transmission electron microscopy. Changes in the crystallinity of the PLA polymer and the model drugs are detected by X‐ray powder diffraction, and the absence of molecular interactions are confirmed by thermal analyses. The results indicate clearly that electrospraying is a potential method for producing polymeric nanoparticles and for encapsulating both hydrophilic and hydrophobic drugs efficiently into the nanoparticles.     

Enhancing the Stability and Immunomodulatory Activity of Liposomal Spherical Nucleic Acids through Lipid‐Tail DNA Modifications

Liposomal spherical nucleic acids (LSNAs) are an attractive therapeutic platform for gene regulation and immunomodulation due to their biocompatibility, chemically tunable structures, and ability to enter cells rapidly without the need for ancillary transfection agents. Such structures consist of small (<100 nm) liposomal cores functionalized with a dense, highly oriented nucleic acid shell, both of which are key components in facilitating their biological activity. Here, the properties of LSNAs synthesized using conventional methods, anchoring cholesterol terminated oligonucleotides into a liposomal core, are compared to LSNAs made by directly modifying the surface of a liposomal core containing azide‐functionalized lipids with dibenzocyclooctyl‐terminated oligonucleotides. The surface densities of the oligonucleotides are measured for both types of LSNAs, with the lipid‐modified structures having approximately twice the oligonucleotide surface coverage. The stabilities and cellular uptake properties of these structures are also evaluated. The higher density, lipid‐functionalized structures are markedly more stable than conventional cholesterol‐based structures in the presence of other unmodified liposomes and serum proteins as evidenced by fluorescence assays. Significantly, this new form of LSNA exhibits more rapid cellular uptake and increased sequence‐specific toll‐like receptor activation in immune reporter cell lines, making it a promising candidate for immunotherapy.     

Colorimetric Detection of Hg2+ Based on the Growth of Aptamer‐Coated AuNPs: The Effect of Prolonging Aptamer Strands

Herein, a versatile and sensitive colorimetric sensor for Hg²⁺ based on aptamer–target specific binding and target‐mediated growth of AuNPs is reported. The 15 T bases are first designed to detect Hg²⁺ through T–Hg²⁺–T coordination. Aptamer–target binding results in the desorption of the aptamer from AuNP surface, the remaining aptamers adsorbed on AuNP surface trigger the growth of AuNPs with morphologically varied nanostructures, and then different colored solutions are formed. On this occasion, the limit of detection (LOD) of 9.6 × 10^?9m is obtained. The other two aptamer strands (25‐ and 59‐mer) are designed by increasing A bases on either side and both sides of 15 T, respectively. The interaction of the binding domain and Hg²⁺ makes desorption of 15 T from AuNP surface, whereas excess bases not committed to the binding domain still adsorbed on AuNP surface. These excess bases control the growth of AuNPs, and enhance the sensitivity. The LODs are 4.05 and 3 × 10^?9m for 25‐ and 59‐mer aptamers, respectively. In addition, the 59‐mer aptamer system is applied to identify Hg²⁺ in real river samples, the LOD of 6.2 × 10^?9m is obtained.     

Facile and Scalable Synthesis of Novel Spherical Au Nanocluster Assemblies@Polyacrylic Acid/Calcium Phosphate Nanoparticles for Dual‐Modal Imaging‐Guided Cancer Chemotherapy

Engineering novel theranostic agents with both imaging and therapeutic functions have profound impact on molecular diagnostics, imaging, and therapeutics. In this paper, we develop for the first time a simple, scalable, and reproducible route to synthesize novel multifunctional spherical Au nanoclusters assemblies encapsulated by a polyacylic acid (PAA)/calcium phosphate (CaP) shell with aggregation enhanced fluorescence property (designated as AuNCs‐A@PAA/CaP). Furthermore, the resulting AuNCs‐A@PAA/CaP nanoparticles (NPs) possess a high payload of doxorubicin as synergetic pH‐sensitive drug delivery vehicles to employ for dual‐modal computed tomography (CT) and fluorescence imaging‐guided liver cancer chemotherapy in vivo. The results reveal that AuNCs‐A@PAA/CaP NPs not only provide excellent bimodal CT and fluorescence contrast imaging but also present efficient tumor ablation under the guidance of CT and fluorescence imaging, to achieve excellent chemotherapeutic efficacy to the hepatocarcinoma cell line (H‐22) bearing mice through intravenous injection. Comprehensive blood tests and careful histological examinations reveal no apparent toxicity of AuNCs‐A@PAA/CaP NPs. Our work highlights the great promise of AuNCs‐A@PAA/CaP NPs for guiding and monitoring the chemotherapeutic process using simultaneous dual‐modality CT and fluorescence imaging through a single theranostic agent.     

Chemical Preparation of Graphene‐Based Nanomaterials and Their Applications in Chemical and Biological Sensors

Graphene is a flat monolayer of carbon atoms packed tightly into a 2D honeycomb lattice that shows many intriguing properties meeting the key requirements for the implementation of highly excellent sensors, and all kinds of proof‐of‐concept sensors have been devised. To realize the potential sensor applications, the key is to synthesize graphene in a controlled way to achieve enhanced solution‐processing capabilities, and at the same time to maintain or even improve the intrinsic properties of graphene. Several production techniques for graphene‐based nanomaterials have been developed, ranging from the mechanical cleavage and chemical exfoliation of high‐quality graphene to direct growth onto different substrates and the chemical routes using graphite oxide as a precusor to the newly developed bottom‐up approach at the molecular level. The current review critically explores the recent progress on the chemical preparation of graphene‐based nanomaterials and their applications in sensors.