Construction of a rapid electrochemical biosensor consisting of a nanozyme/aptamer conjugate for waterborne microcystin detection.

Microcystin-LR (MC-LR) is a hepatotoxin generated by the excessive proliferation of cyanobacteria, which is a threat to humans and wildlife. Therefore, rapid detection of MC-LR is an important challenge. This study describes a rapid electrochemical biosensor comprising nanozymes and aptamers. Alternating current electrothermal flow (ACEF) significantly reduced the MC-LR detection period to 10 min. We also used MnO2/MC-LR aptamer conjugates to improve the sensitivity to MC-LR detection. Here, MnO2 amplified the electrochemical signal and the aptamer showed high selectivity for MC-LR. Under the optimal conditions, the limit of detection (LOD) and selectivity in freshwater were detected using cyclic voltammetry and differential pulse voltammetry. As a result, an LOD of 3.36 pg mL-1 was observed in the linear concentration range of 10 pg mL-1 to 1 µg mL-1. This study quickly and sensitively detected MC-LR in a situation where it causes serious damage worldwide. In addition, the ACEF technology introduction is the first example of MC-LR detection, suggesting a wide range of possibilities for MC-LR biosensors.

Bifunctional Au@Bi2 Se3 Core-Shell Nanoparticle for Synergetic Therapy by SERS-Traceable AntagomiR Delivery and Photothermal Treatment.

For the first time, topological insulator bismuth selenide nanoparticles (Bi2 Se3 NP) are core-shelled with gold (Au@Bi2 Se3 ) i) to represent considerably small-sized (11 nm) plasmonic nanoparticles, enabling accurate bioimaging in the near-infrared region; ii) to substantially improve Bi2 Se3 biocompatibility, iii) water dispersibility, and iv) surface functionalization capability through straightforward gold-thiol interaction. The Au@Bi2 Se3 is subsequently functionalized for v) effective targeting of SH-SY5Y cancer cells, vi) disrupting the endosome/lysosome membrane, vii) traceable delivery of antagomiR-152 and further synergetic oncomiR knockdown and photothermal therapy (PTT). Unprecedentedly, it is observed that the Au shell thickness has a significant impact on evoking the exotic plasmonic features of Bi2 Se3 . The Au@Bi2 Se3 possesses a high photothermal conversion efficiency (35.5%) and a remarkable surface plasmonic effect (both properties are approximately twofold higher than those of 50 nm Au nanoparticles). In contrast to the siRNA/miRNA delivery methods, the antagomiR delivery is based on strand displacement, in which the antagomiR-152 is displaced by oncomiR-152 followed by a surface-enhanced Raman spectroscopy signal drop. This enables both cancer cell diagnosis and in vitro real-time monitoring of the antagomiR release. This selective PTT nanoparticle can also efficiently target solid tumors and undergo in vivo PTT, indicating its potential clinical applications.

Application of Gold Nanoparticle to Plasmonic Biosensors.

Gold nanoparticles (GNPs) have been widely utilized to develop various biosensors for molecular diagnosis, as they can be easily functionalized and exhibit unique optical properties explained by plasmonic effects. These unique optical properties of GNPs allow the expression of an intense color under light that can be tuned by altering their size, shape, composition, and coupling with other plasmonic nanoparticles. Additionally, they can also enhance other optical signals, such as fluorescence and Raman scattering, making them suitable for biosensor development. In this review, we provide a detailed discussion of the currently developed biosensors based on the aforementioned unique optical features of GNPs. Mainly, we focus on four different plasmonic biosensing methods, including localized surface plasmon resonance (LSPR), surface-enhanced Raman spectroscopy (SERS), fluorescence enhancement, and quenching caused by plasmon and colorimetry changes based on the coupling of GNPs. We believe that the topics discussed here are useful and able to provide a guideline in the development of novel GNP-based biosensors in the future.

Extracellular vesicles as nanotheranostic platforms for targeted neurological disorder interventions.

Central Nervous System (CNS) disorders represent a profound public health challenge that affects millions of people around the world. Diseases such as Alzheimer's disease (AD), Parkinson's disease (PD), and traumatic brain injury (TBI) exemplify the complexities and diversities that complicate their early detection and the development of effective treatments. Amid these challenges, the emergence of nanotechnology and extracellular vesicles (EVs) signals a new dawn for treating and diagnosing CNS ailments. EVs are cellularly derived lipid bilayer nanosized particles that are pivotal in intercellular communication within the CNS and have the potential to revolutionize targeted therapeutic delivery and the identification of novel biomarkers. Integrating EVs with nanotechnology amplifies their diagnostic and therapeutic capabilities, opening new avenues for managing CNS diseases. This review focuses on examining the fascinating interplay between EVs and nanotechnology in CNS theranostics. Through highlighting the remarkable advancements and unique methodologies, we aim to offer valuable perspectives on how these approaches can bring about a revolutionary change in disease management. The objective is to harness the distinctive attributes of EVs and nanotechnology to forge personalized, efficient interventions for CNS disorders, thereby providing a beacon of hope for affected individuals. In short, the confluence of EVs and nanotechnology heralds a promising frontier for targeted and impactful treatments against CNS diseases, which continue to pose significant public health challenges. By focusing on personalized and powerful diagnostic and therapeutic methods, we might improve the quality of patients.

Enhancing CAR Macrophage Efferocytosis Via Surface Engineered Lipid Nanoparticles Targeting LXR Signaling.

The removal of dying cells, or efferocytosis, is an indispensable part of resolving inflammation. However, the inflammatory microenvironment of the atherosclerotic plaque frequently affects the biology of both apoptotic cells and resident phagocytes, rendering efferocytosis dysfunctional. To overcome this problem, a chimeric antigen receptor (CAR) macrophage that can target and engulf phagocytosis-resistant apoptotic cells expressing CD47 is developed. In both normal and inflammatory circumstances, CAR macrophages exhibit activity equivalent to antibody blockage. The surface of CAR macrophages is modified with reactive oxygen species (ROS)-responsive therapeutic nanoparticles targeting the liver X receptor pathway to improve their cell effector activities. The combination of CAR and nanoparticle engineering activated lipid efflux pumps enhances cell debris clearance and reduces inflammation. It is further suggested that the undifferentiated CAR-Ms can transmigrate within a mico-fabricated vessel system. It is also shown that our CAR macrophage can act as a chimeric switch receptor (CSR) to withstand the immunosuppressive inflammatory environment. The developed platform has the potential to contribute to the advancement of next-generation cardiovascular disease therapies and further studies include in vivo experiments.

Nanotechnology-Assisted Biosensors for the Detection of Viral Nucleic Acids: An Overview.

The accurate and rapid diagnosis of viral diseases has garnered increasing attention in the field of biosensors. The development of highly sensitive, selective, and accessible biosensors is crucial for early disease detection and preventing mortality. However, developing biosensors optimized for viral disease diagnosis has several limitations, including the accurate detection of mutations. For decades, nanotechnology has been applied in numerous biological fields such as biosensors, bioelectronics, and regenerative medicine. Nanotechnology offers a promising strategy to address the current limitations of conventional viral nucleic acid-based biosensors. The implementation of nanotechnologies, such as functional nanomaterials, nanoplatform-fabrication techniques, and surface nanoengineering, to biosensors has not only improved the performance of biosensors but has also expanded the range of sensing targets. Therefore, a deep understanding of the combination of nanotechnologies and biosensors is required to prepare for sanitary emergencies such as the recent COVID-19 pandemic. In this review, we provide interdisciplinary information on nanotechnology-assisted biosensors. First, representative nanotechnologies for biosensors are discussed, after which this review summarizes various nanotechnology-assisted viral nucleic acid biosensors. Therefore, we expect that this review will provide a valuable basis for the development of novel viral nucleic acid biosensors.

Enzymatic Electrochemical/Fluorescent Nanobiosensor for Detection of Small Chemicals.

The detection of small molecules has attracted enormous interest in various fields, including the chemical, biological, and healthcare fields. In order to achieve such detection with high accuracy, up to now, various types of biosensors have been developed. Among those biosensors, enzymatic biosensors have shown excellent sensing performances via their highly specific enzymatic reactions with small chemical molecules. As techniques used to implement the sensing function of such enzymatic biosensors, electrochemical and fluorescence techniques have been mostly used for the detection of small molecules because of their advantages. In addition, through the incorporation of nanotechnologies, the detection property of each technique-based enzymatic nanobiosensors can be improved to measure harmful or important small molecules accurately. This review provides interdisciplinary information related to developing enzymatic nanobiosensors for small molecule detection, such as widely used enzymes, target small molecules, and electrochemical/fluorescence techniques. We expect that this review will provide a broad perspective and well-organized roadmap to develop novel electrochemical and fluorescent enzymatic nanobiosensors.

An Updated Review on Electrochemical Nanobiosensors for Neurotransmitter Detection.

Neurotransmitters are chemical compounds released by nerve cells, including neurons, astrocytes, and oligodendrocytes, that play an essential role in the transmission of signals in living organisms, particularly in the central nervous system, and they also perform roles in realizing the function and maintaining the state of each organ in the body. The dysregulation of neurotransmitters can cause neurological disorders. This highlights the significance of precise neurotransmitter monitoring to allow early diagnosis and treatment. This review provides a complete multidisciplinary examination of electrochemical biosensors integrating nanomaterials and nanotechnologies in order to achieve the accurate detection and monitoring of neurotransmitters. We introduce extensively researched neurotransmitters and their respective functions in biological beings. Subsequently, electrochemical biosensors are classified based on methodologies employed for direct detection, encompassing the recently documented cell-based electrochemical monitoring systems. These methods involve the detection of neurotransmitters in neuronal cells in vitro, the identification of neurotransmitters emitted by stem cells, and the in vivo monitoring of neurotransmitters. The incorporation of nanomaterials and nanotechnologies into electrochemical biosensors has the potential to assist in the timely detection and management of neurological disorders. This study provides significant insights for researchers and clinicians regarding precise neurotransmitter monitoring and its implications regarding numerous biological applications.

Noble Metal Nanomaterial-Based Biosensors for Electrochemical and Optical Detection of Viruses Causing Respiratory Illnesses.

Noble metal nanomaterials, such as gold, silver, and platinum, have been studied extensively in broad scientific fields because of their unique properties, including superior conductivity, plasmonic property, and biocompatibility. Due to their unique properties, researchers have used them to fabricate biosensors. Recently, biosensors for detecting respiratory illness-inducing viruses have gained attention after the global outbreak of coronavirus disease (COVID-19). In this mini-review, we discuss noble metal nanomaterials and associated biosensors for detecting respiratory illness-causing viruses, including SARS-CoV-2, using electrochemical and optical detection techniques. this review will provide interdisciplinary knowledge about the application of noble metal nanomaterials to the biomedical field.

Nano-sized graphene oxide coated nanopillars on microgroove polymer arrays that enhance skeletal muscle cell differentiation.

The degeneration or loss of skeletal muscles, which can be caused by traumatic injury or disease, impacts most aspects of human activity. Among various techniques reported to regenerate skeletal muscle tissue, controlling the external cellular environment has been proven effective in guiding muscle differentiation. In this study, we report a nano-sized graphene oxide (sGO)-modified nanopillars on microgroove hybrid polymer array (NMPA) that effectively controls skeletal muscle cell differentiation. sGO-coated NMPA (sG-NMPA) were first fabricated by sequential laser interference lithography and microcontact printing methods. To compensate for the low adhesion property of polydimethylsiloxane (PDMS) used in this study, graphene oxide (GO), a proven cytophilic nanomaterial, was further modified. Among various sizes of GO, sGO (< 10 nm) was found to be the most effective not only for coating the surface of the NM structure but also for enhancing the cell adhesion and spreading on the fabricated substrates. Remarkably, owing to the micro-sized line patterns that guide cellular morphology to an elongated shape and because of the presence of sGO-modified nanostructures, mouse myoblast cells (C2C12) were efficiently differentiated into skeletal muscle cells on the hybrid patterns, based on the myosin heavy chain expression levels. Therefore, the developed sGO coated polymeric hybrid pattern arrays can serve as a potential platform for rapid and highly efficient in vitro muscle cell generation.

Flexible Electronics for Monitoring in vivo Electrophysiology and Metabolite Signals.

Numerous efforts have been made to develop efficient biosensors for detecting analytes in the human body. However, biosensors are often developed on rigid materials, which limits their application on skin, organs, and other tissues in the human body where good flexibility is required. Developing flexible materials for biosensors that can be used on soft and irregularly shaped surfaces would significantly expand the clinical application of biosensors. In this review, we will provide a selective overview of recently developed flexible electronic devices and their applications for monitoring in vivo metabolite and electrophysiology signals. The article provides guidelines for the development of an in vivo signal monitoring system and emphasizes research from various disciplines for the further development of flexible electronics that can be used in more biomedical applications in the future.

Flexible electrochemical biosensors for healthcare monitoring.

As the interest in wearable devices has increased recently, increasing biosensor flexibility has begun to attract considerable attention. Among the various types of biosensors, electrochemical biosensors are uniquely suited for the development of such flexible biosensors due to their many advantages, including their fast response, inherent miniaturization, convenient operation, and portability. Therefore, many studies on flexible electrochemical biosensors have been conducted in recent years to achieve non-invasive and real-time monitoring of body fluids such as tears, sweat, and saliva. To achieve this, various substrates, novel nanomaterials, and detection techniques have been utilized to develop conductive flexible platforms that can be applied to create flexible electrochemical biosensors. In this review, we discussed recently reported flexible electrochemical biosensors and divided them into specific categories including materials for flexible substrate, fabrication techniques for flexible biosensor development, and recently developed flexible electrochemical biosensors to externally monitor target molecules, thereby providing a means to noninvasively examine cells and body fluid samples. In conclusion, this review will discuss the materials, methods, recent studies, and perspectives on flexible electrochemical biosensors for healthcare monitoring and wearable biosensing systems.

Functional nanoarrays for investigating stem cell fate and function.

Stem cells show excellent potential in the field of tissue engineering and regenerative medicine based on their excellent capability to not only self-renew but also differentiate into a specialized cell type of interest. However, the lack of a non-destructive monitoring system makes it challenging to identify and characterize differentiated cells before their transplantation without compromising cell viability. Thus, the development of a non-destructive monitoring method for analyzing cell function is highly desired and can significantly benefit stem cell-based therapies. Recently, nanomaterial-based scaffolds (e.g., nanoarrays) have made possible considerable advances in controlling the differentiation of stem cells and characterization of the differentiation status sensitively in real time. This review provides a selective overview of the recent progress in the synthesis methods of nanoarrays and their applications in controlling stem cell fate and monitoring live cell functions electrochemically. We believe that the topics discussed in this review can provide brief and concise guidelines for the development of novel nanoarrays and promote the interest in live cell study applications. A method which can not only control but also monitor stem cell fate and function will be a promising technology that can accelerate stem cell therapies.

Single Functionalized pRNA/Gold Nanoparticle for Ultrasensitive MicroRNA Detection Using Electrochemical Surface-Enhanced Raman Spectroscopy.

Controlling the selective one-to-one conjugation of RNA with nanoparticles is vital for future applications of RNA nanotechnology. Here, the monofunctionalization of a gold nanoparticle (AuNP) with a single copy of RNA is developed for ultrasensitive microRNA-155 quantification using electrochemical surface-enhanced Raman spectroscopy (EC-SERS). A single AuNP is conjugated with one copy of the packaging RNA (pRNA) three-way junction (RNA 3WJ). pRNA 3WJ containing one strand of the 3WJ is connected to a Sephadex G100 aptamer and a biotin group at each arm (SEPapt/3WJ/Bio) which is then immobilized to the Sephadex G100 resin. The resulting complex is connected to streptavidin-coated AuNP (STV/AuNP). Next, the STV/AuNP-Bio/3WJa is purified and reassembled with another 3WJ to form a single-labeled 3WJ/AuNP. Later, the monoconjugate is immobilized onto the AuNP-electrodeposited indium tin oxide coated substrate for detecting microRNA-155 based on EC-SERS. Application of an optimum potential of +0.2 V results in extraordinary amplification (≈7 times) of methylene blue (reporter) SERS signal compared to the normal SERS signal. As a result, a highly sensitive detection of 60 × 10-18 m microRNA-155 in 1 h in serum based on monoconjugated AuNP/RNA is achieved. Thus, the monofunctionalization of RNA onto nanoparticle can provide a new methodology for biosensor construction and diverse RNA nanotechnology development.

Multifunctional Nanobiohybrid Material Composed of Ag@Bi2Se3/RNA Three-Way Junction/miRNA/Retinoic Acid for Neuroblastoma Differentiation.

Nanoparticle-based cell differentiation therapy has attracted increasing research interest as it is a promising substitute for conventional cancer treatment methods. Here, the topological insulator bismuth selenide nanoparticle (Bi2Se3 NP) was core-shelled with silver (Ag@Bi2Se3) to represent remarkable biocompatibility and plasmonic features (ca. 2.3 times higher than those of Ag nanoparticle). Moreover, a newly developed RNA three-way junction (3WJ) structure was designed for the quad-functionalization of any type of nanoparticle and surface. One leg of the 3WJ was attached to the Ag@Bi2Se3, and the other leg harbored a cell-penetrating RNA and a florescence tag. The third leg was designed to inhibit micro-RNA-17 (miR-17) and to further release retinoic acid (RA). A new drug delivery mechanism was developed for the slow release of RA inside the cytosol based on the prerequisite inhibition of miR-17 using a strand displacement strategy. In this paper, we report a simple methodology for resolving the hydrophobicity challenges of RA by its conjugation with a RNA strand (RA/R) through a stimulus-responsive cross-linker. The developed nanobiohybrid material could fully differentiate SH-SY5Y cancer cells into neurons and stop their growth in 6 days without requiring sequential treatments which has not been reported yet. Using a surface-enhanced Raman spectroscopy technique, the RA delivery and the cell differentiation process were monitored nondestructively in real time. The fabricated nanobiohybrid material could open the new horizons in the fabrication of different diagnostic/therapeutic agents.

Flexible electrochemical glucose biosensor based on GOx/gold/MoS2/gold nanofilm on the polymer electrode.

The need for flexible biosensors has increased because of their potential applications for point-of-care diagnosis and wearable biosensors. However, flexible biosensors have low sensitivity due to the flexibility of the electrode, and their fabrication involves complex processes. To overcome these limitations, a flexible electrochemical enzyme biosensor was developed in this study by immobilizing an enzyme on the flexible polymer electrode modified with a gold/MoS2/gold nanofilm. The fabrication process involved sputter deposition of gold, spin coating of MoS2, and sputter deposition of gold on the flexible polymer electrode (commercially available Kapton® polyimide film). The flexible glucose biosensor was made by immobilization of glucose oxidase on a flexible electrode by using a chemical linker. The detection limit for glucose was estimated to be 10 nM, which indicates more sensitivity as compared with a previously reported flexible glucose sensor. This sensitivity is due to the facilitation of electron transfer by MoS2. The flexure extension of this biosensor was estimated at 3.48 mm, which is much higher than that of the rigid sensor using a gold-coated silicon electrode (0.09 mm), according to measurements with a micro-fatigue tester. The proposed flexible biosensor composed of the enzyme/gold/MoS2/gold nanofilm on the polymer electrode can be used as a flexible sensing platform for developing wearable biosensing systems because of its high sensitivity, high flexibility, and simple fabrication process.

Nondestructive Real-Time Monitoring of Enhanced Stem Cell Differentiation Using a Graphene-Au Hybrid Nanoelectrode Array.

Stem cells have attracted increasing research interest in the field of regenerative medicine because of their unique ability to differentiate into multiple cell lineages. However, controlling stem cell differentiation efficiently and improving the current destructive characterization methods for monitoring stem cell differentiation are the critical issues. To this end, multifunctional graphene-gold (Au) hybrid nanoelectrode arrays (NEAs) to: (i) investigate the effects of combinatorial physicochemical cues on stem cell differentiation, (ii) enhance stem cell differentiation efficiency through biophysical cues, and (iii) characterize stem cell differentiation in a nondestructive real-time manner are developed. Through the synergistic effects of physiochemical properties of graphene and biophysical cues from nanoarrays, the graphene-Au hybrid NEAs facilitate highly enhanced cell adhesion and spreading behaviors. In addition, by varying the dimensions of the graphene-Au hybrid NEAs, improved stem cell differentiation efficiency, resulting from the increased focal adhesion signal, is shown. Furthermore, graphene-Au hybrid NEAs are utilized to monitor osteogenic differentiation of stem cells electrochemically in a nondestructive real-time manner. Collectively, it is believed the unique multifunctional graphene-Au hybrid NEAs can significantly advance stem-cell-based biomedical applications.