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The exploration of multifunctional nanomedicine has prompted interest in improving glioblastoma (GBM) prognosis. In this study, we constructed tumor microenvironment (TME)-responsive magnetic therapeutic nanoparticles (BK@MTNPs) as a multifunctional drug delivery platform. It contains the following components. [Des-arg(Sheets et al., 2020 [9])]bradykinin (BK), which contributes to the transient opening of the blood-brain barrier (BBB) and targeting of GBM cells; nanoparticles (NPs) encapsulated in MTNPs, which act as an in vivo magnetic resonance (MR) imaging agent; crizotinib, which is an inhibitor of protein kinase c-Met; and the immune drug anti-PDL1 antibody. These components were loaded into BK@MTNPs for complete tumoricidal effects. Abundant glutathione in the TME can promote BK@MTNP degradation by interrupting the disulfide bonds between cysteine residues. Such BK@MTNPs support a synergistic tumoricidal effect by inducing DNA damage, activating the transcription of the tumor suppressor gene PTEN, inhibiting glioblastoma stem cell function, activating cytotoxic T lymphocytes, and reprogramming tumor-associated macrophages. BK@MTNPs showed a significant increase in antitumor activity compared with free drugs in vitro. Furthermore, in mice bearing orthotopic GBM, treatment with BK@MTNPs resulted in marked tumor inhibition and greatly extended survival time with minimal side effects. This study demonstrates the advantages of chemo-immunotherapeutic NPs accumulated in the GBM area and their effective inhibition of GBM growth, thus establishing a delivery platform to promote antitumor immunity against GBM.

Glioblastoma stem cells (GSCs) are subpopulations of tumor-initiating cells responsible for glioblastoma (GBM) tumorigenesis and recurrence. Dual inhibition of vascular endothelium and GSCs is still a challenge due to their different pathological features. Here we present a combined all-in-control strategy to realize a local photothermal therapy (PTT). We designed T-cell-mimic nanoparticles with aggregation-induced emission (AIE) characteristics by coating the genetically engineered T cell membrane (CM) onto AIE nanoparticles (CM@AIE NPs). The CM shell was designed against CD133 and epidermal growth factor receptor (EGFR) which provides the possibility to target both GBM cells and GSCs for cancer therapy. CM@AIE NPs can serve as the tight junction (TJ) modulators to trigger an intracellular signaling cascade, causing TJ disruption and actin cytoskeleton reorganization to allow CM@AIE NPs to cross the blood-brain barrier (BBB) silently. The 980 nm excitation-triggered PTT can completely inhibit tumorigenesis and recurrence. The combination of CM-coating nanotechnology and genetic editing technique can inspire further development of synergetic techniques for preventing GBM recurrence.

Nanozyme-based catalytic therapy, an emerging therapeutic pattern, has significantly incorporated in the advancement of tumor therapy by generating lethal reactive oxygen species. Nevertheless, most of the nanozymes have mono catalytic performances with H

Biomolecules have been widely studied for bioelectronic application including biosensors, biomedical devices, biocomputation devices. Among them, the resistive switching biodevices have been developed to demonstrate the resistive switching function based on biomolecules. However, resistive switching biodevices developed so far have some limitations such as narrow voltage range and low stability for practical application. In this study, a heterolayer composed of carboxyl-modified molybdenum disulfide nanoparticles (MoS2) and DNA on the gold (Au) electrode was developed to achieve a wide voltage range and high stability at the nanoscale. To fabricate the resistive switching biodevices, a DNA layer was formed on the electrode through the thiol group on the DNA. The carboxyl-modified MoS2 was then immobilized on the DNA layer (MoS2-DNA heterolayer) through the EDC/NHS reaction. For analyzing the electrical properties, the scanning tunneling spectroscopy investigation showed the resistive switching function of a wide voltage range (4.0 V to −4.0 V) and high stability (10 days) on the MoS2-DNA heterolayer of Au electrodes. The conductivity dramatically increased when the voltage reached 2.4 V, whereas the conductivity abruptly decreased when the voltage reached 0.01 V. From results, we proposed that a MoS2-DNA heterolayer on Au electrode could be utilized as a nanoscale resistive switching layer for the development of nanoscale bioelectronic devices with a wide voltage range and high stability. Based on those advantages, the introduction of MoS2/DNA heterolayer can offer the new direction for development of novel bioelectronic devices.

Avian influenza virus (AIV) is one of the most harmful pathogens to living things due to its fast infection, various mutations, and dangerous symptoms. In this study, we fabricated a label-free AIV H5N1 biosensor composed of multi-functional DNA structure on a porous Au nanoparticles (pAuNPs) fabricated electrode using the electrochemical (EC) technique. As a multi-functional bioprobe, the DNA 3 way-junction (3WJ) was introduced. Each fragment of DNA 3WJ was rolled to recognition part (hemagglutinin (HA) protein detection aptamer), EC signal generation part (horseradish peroxidase (HRP)-mimicked DNAzyme), and immobilization part (Thiol group). Each fragment was assembled in order to form the DNA 3WJ for AI detection and the assembled structure was confirmed by native-tris boric acid magnesium polyacrylamide gel electrophoresis (TBM-PAGE). Moreover, in order to increase the electrochemical signal sensitivity, pAuNPs were synthesized. The property of pAuNPs was investigated by field emission scanning electron microscopy (FE-SEM), Transmission electron microscopy (TEM), Ultraviolet–visible (UV-VIS) spectroscopy and zeta potential analysis. The DNA 3WJ on pAuNPs-modified Au electrode was then prepared using the layer-by-layer (LbL) assembly method. FE-SEM and atomic force microscopy (AFM) were used to investigate the surface morphology. Cyclic voltammetry (CV) was carried out to confirm the HA protein binding to DNA 3WJ-modified electrode. Moreover, The HA protein can be detected 1 pM in HEPES solution and 1 pM in diluted-chicken serum, respectively. The present study showed label-free, simple fabrication, and easy-to-tailor detection elements for AIV. The present biosensor can be a powerful candidate for various virus detection platforms.

Infectious pancreatic necrosis virus (IPNV) has been identified as a viral pathogen for many fish diseases that have become a huge hurdle for the growing fishing industry. Thus, in this work, we report a label-free impedance biosensor to quantify IPNV in real fish samples at point-of-care (POC) level. High specificity IPNV sensor with a detection limit of 2.69 TCID50/mL was achieved by conjugating IPNV antibodies to portable Au disk electrode chips using human heavy chain apoferritin (H-AFN) nanoprobes as a binding agent. H-AFN probes were bioengineered through PCR by incorporating pET-28b(+) resulting in 24 subunits of 6 × his-tag and protein-G units on its outer surface to increase the sensitivity of the IPNV detection. The biosensor surface modifications were characterized by differential pulse voltammetry (DPV) and EIS methods for each modification step. The proposed nanoprobe based sensor showed three-fold enhancement in charge transfer resistance toward IPNV detection in comparison with the traditional linker approach when measured in a group of similar virus molecules. The portable sensor exhibited a linear range of 100-10000 TCID50/mL and sensitivity of 5.40 × 10-4 TCID50/mL in real-fish samples. The performance of the proposed IPNV sensor was fully validated using an enzyme-linked immunosorbent assay (ELISA) technique with a sensitivity of 3.02 × 10-4 TCID50/mL. Results from H-AFN nanoprobe based IPNV sensor indicated high selectivity, sensitivity, and stability could be a promising platform for the detection of similar fish viruses and other biological molecules of interest.

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 hydr...

Oxidative stress and local overactive inflammation have been considered major obstacles in diabetic wound treatment. Although antiphlogistic tactics have been reported widely, they are also challenged by pathogen contamination and compromised angiogenesis. Herein, a versatile integrated nanoagent based on 2D reductive covalent organic frameworks coated with antibacterial immuno-engineered exosome (PCOF@E-Exo) is reported to achieve efficient and comprehensive combination therapy for diabetic wounds. The E-Exo is collected from TNF-α-treated mesenchymal stem cells (MSCs) under hypoxia and encapsulated cationic antimicrobial carbon dots (CDs). This integrated nanoagent not only significantly scavenges reactive oxygen species and induces anti-inflammatory M2 macrophage polarization, but also stabilizes hypoxia-inducible factor-1α (HIF-1α). More importantly, the PCOF@E-Exo exhibits intriguing bactericide capabilities toward Gram-negative, Gram-positive, and drug-resistant bacteria, showing favorable intracellular bacterial destruction and biofilm permeation. In vivo results demonstrate that the synergetic impact of suppressing oxidative injury and tissue inflammation, promoting angiogenesis and eradicating bacterial infection, could significantly accelerate the infected diabetic fester wound healing with better therapeutic benefits than monotherapy or individual antibiotics. The proposed strategy can inspire further research to design more delicate platforms using the combination of immunotherapy with other therapeutic methods for more efficient ulcerated diabetic wounds treatments.

Background: In recent decades, contaminations with heavy metals ions have adversely affected the environment, food safety, and human health. Heavy metals, leaching to water sources from the industrial effluents, can enter into the aquatic and food chains of humans and animals from a variety of anthropogenic sources. Scope and Approach: Heavy metal detection has been an intensive area of research today. Both laboratory-based analytical instruments and innovative sensor devices like the electronic nose, electronic tongue, and bio/chemical sensors have increasingly emerged to meet the demand for legislative actions on environmental pollution control and early warning. These evolving technology and developments particularly in the area of nanotechnology and sensors have become key contributing factors in heavy metal detection. Key Findings and Conclusions: This endeavor aims at exploring this field in detail to understand the key principles behind this flourishing science and summarize the recent development in heavy metal detection technologies. This article also gives a brief review of commercially available portable devices that has the potential to become the next gold standard instruments in heavy metal detection.

Compared to other tumors, glioblastoma (GBM) is extremely difficult to treat. Recently, photothermal therapy (PTT) has demonstrated advanced therapeutic efficacy; however, because of the relatively low tissue-penetration efficiency of laser light, its application in deep-seated tumors remains challenging. Herein, bradykinin (BK) aggregation-induced-emission nanoparticles (BK@AIE NPs) are synthesized; these offer selective penetration through the blood–tumor barrier (BTB) and strong absorbance in the near-infrared region (NIR). The BK ligand can prompt BTB adenosine receptor activation, which enhances transportation and accumulation inside tumors, as confirmed by T1-weighted magnetic resonance and fluorescence imaging. The BK@AIE NPs exhibit high photothermal conversion efficiency under 980 nm NIR laser irradiation, facilitating the treatment of deep-seated tumors. Tumor progression can be effectively inhibited to extend the survival span of mice after spatiotemporal PTT. NIR irradiation can eradicate tumor tissues and release tumor-associated antigens. It is observed that the PTT treatment of GBM-bearing mice activates natural killer cells, CD3+ T cells, CD8+ T cells, and M1 macrophages in the GBM area, increasing the therapeutic efficacy. This study demonstrates that NIR-assisted BK@AIE NPs represent a promising strategy for the improved systematic elimination of GBMs and the activation of local brain immune privilege.

Lactoferrin is a multifunctional protein of the transferrin family and is known as a biomarker for various clinical diseases including urinary tract infection (UTI). However, wide concentration range of lactoferrin in urine samples due to the high interpatient variations, requires a more practical biosensor. In this article, we used a novel multivalent aptamer immobilized on the surface of screen-printed gold electrode (aptamer/SPGE) to develop the first electrochemical aptasensor for label-free detection of lactoferrin with wide dynamic detection range and high sensitivity. The performance of the fabricated biosensor was tested using electrochemical impedance spectroscopy and differential pulse voltammetry. The multivalent aptamer as the bioreceptor with high affinity and good specificity against human lactoferrin, acts to enhance the electrochemical signals and widen the working window. The aptamer/SPGE demonstrates superior sensing performances for lactoferrin in buffer solution, with a wide linear range of 10 to 1300 ng/mL with LOD of 0.9 ng/mL, as well as high selectivity, and excellent reproducibility. Besides, the constructed aptasensor was successfully applied to quantify lactoferrin concentrations in spiked urine solutions. Owing to excellent sensitivity, ease of miniaturization, simple sensing procedure, low-cost, and fast response, the proposed electrochemical aptasensor indicates a great potential towards the development of lactoferrin analysis systems, which would be helpful in the early diagnosis of UTI.

Graphene oxide (GO) is a well-known two-dimensional nanomaterial with broad applications in various fields. In particular, the functional groups of GO has demonstrated significance in the molecular binding interactions. GO is normally coated on a solid surface as it is difficult to handle due to its nano-scaled size. Therefore, chemical properties of surface-coated GO depend on the morphological structure of GO on the surface and the operating conditions during the coating process. Isolation of bacteria from environmental samples such as river and pond water is important for increasing the analytical sensitivity of sensor devices. The main issue in isolation of bacteria from an environmental sample is adsorption capacity per unit time. However, increasing the velocity of water sample to elevate the process rate induces high shear stress on the surface, such that the bacteria adsorption rate on the surface is reduced. In this study, we investigated the morphological and chemical properties of sonicated GO and GO-coated surface by atomic force microscopy (AFM) and X-ray photoelectron spectroscopy (XPS). The sonicated GO-coated beads were successfully used for concentrating bacteria from a large-volume sample as opposed to the conventional methods. It can be concluded that, GO-coated surfaces are prospective platforms for concentrating bacteria from various samples and play a major role in reducing the concentration time.

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., A monofunctionalized gold nanoparticle (GNP)/RNA structure is fabricated using a packaging RNA three‐way junction motif of the bacteriophage phi29 DNA packaging motor. The structure is further engaged to form a rigid λ‐shaped bioprobe RNA architecture onto the GNP–electrodeposited indium tin oxide coated substrate for highly sensitive and specific detection of microRNAs down to 60 × 10−18 m by means of electrochemical surface‐enhanced Raman spectroscopy.

We fabricated a microRNA biosensor using the combination of surface enhanced Raman spectroscopy (SERS) and electrochemical (EC) techniques. For the first time, the weaknesses of each techniques for microRNA detection was compensated by the other ones to give rise to the specific and wide-range detection of miR-155. A single stranded 3′ methylene blue (MB) and 5′ thiol-modified RNA (MB-ssRNA-SH) was designed to detect the target miR-155 and immobilized onto the gold nanoparticle-modified ITO (ITO/GNP). Upon the invasion of target strand, the double-stranded RNA transformed rapidly to an upright structure resulting in a notable decrease in SERS and redox signals of the MB. For the first time, by combination of SERS and EC techniques in a single platform we extended the dynamic range of both techniques from 10 pM to 450 nM (SERS: 10 pM–5 nM and EC: 5 nM–450 nM). As well, the SERS technique improved the detection limit of the EC method from 100 pM to 100 fM, while the EC method covered single-mismatch detection which was the SERS deficiency. The fabricated single-step biosensor possessing a good capability of miRNA detection in human serum, could be employed throughout the broad ranges of biomedical and bioelectronics applications.

Nitric oxide (NO) is one of the most important molecules in living things due to its role as a signaling molecule in influencing pathological and physiological mechanisms including neurotransmission. In this study, the electrochemical biosensor based on the amine-modified molybdenum disulfide nanoparticles (MoS2), graphene oxide (GO) and myoglobin (Mb) hybrid material (amine-modified MoS2/GO/Mb hybrid) is developed to achieve the accurate detection of NO with electrochemical signal improvement. For the first time, the synthesis of MoS2 accompanying the amine-modification of the surface of MoS2 is done to hybridize with GO efficiently through the short linkage. After the amine-modification of MoS2, it is enclosed with GO directly (amine-modified MoS2/GO). Then, Mb which can induce the reduction of NO is immobilized on the amine-modified MoS2/GO to fabricate the amine-modified MoS2/GO/Mb hybrid for NO detection. The prepared hybrid shows the signal improved redox properties relative to the result of the electrode prepared without hybrid. Furthermore, upon addition of NO, the electrode prepared with hybrid shows the improved amperometric response compared with that of the electrode without hybrid. This amine-modified MoS2/GO/Mb hybrid can be used in the development of the biosensor platform accompanying the electrochemical signal improvement and accurate detection of target materials.

Several challenges remained to fabricate a molecular-level nucleic acid biosensor such as surface immobilization control, single mismatch detection and low current response. To overcome those issues, for the first time, authors presented a novel parallel structural dsDNA/recombinant azurin (PSD/rAzu) hybrid structure for the general nucleic acid detection. The PSD was designed and introduced by the optimized 8 Ag+ ions to have greater conductivity than the canonical dsDNA, and conjugated with rAzu to develop a general platform for electrochemical detection of miRNAs and viral DNAs with high reproducibility and ultra-sensitivity towards single base pair mutation. Thanks to the bifunctional rAzu as the selective spacer and electrochemical signal mediator, in the presence of the target strand, the imperfect PSD switched rapidly to the upright position where the Ag+ ions intercalated between C-C mismatches of dsDNAs at the top of each structure brought further from the electrode surface resulting in a significant electrochemical signal drop of the Ag+ ions. The charge transfer (CT) mechanism across the hybrid structure was simply clarified on the basis of the redox potential location of the species. The electrical conductivity of DNAs were measured using scanning tunneling spectroscopy (STS) at the molecular scale and cyclic voltammetry (CV) technique based on the reduction of Ag+ ion. The proposed PSD/rAzu hybrid structure with a great capability of single mutation recognition and miRNA expression level profiling in cancer cells holds a very promising platform to be studied for further development of various kinds of nanoscale biosensors, bioelectronic devices., Highlights • We fabricated a novel parallel structural dsDNA/recombinant azurin (PSD/rAzu) hybrid structure for nucleic acid detection. • The PSD was designed and introduced by the optimized 8 Ag+ ions to have higher conductivity than the canonical dsDNA. • The PSD/rAzu functioned as a general platform for electrochemical detection of miRNAs and viral DNAs with high sensitivity. • The charge transfer mechanism across the hybrid structure was clarified based on the redox potential location of the species.

In this paper a novel method called Vector Analysis (VA), using a new instability detection index is proposed to provide wide area voltage stability for the power systems. The index extraction process relies on measurements of active and reactive powers from connected buses to the generator bus. Moreover, as long as VA predicts voltage collapse, through disconnecting weak lines and based on network graph, zoning is carried out in the power system. For the aim of system observability, phasor measurement units (PMUs) placement, have also been optimized by Swarm Robotics Search & Rescue (SRSR) algorithm. Simulations have been carried out on IEEE 39- bus test system which demonstrates the accuracy of index distinction in voltage stability assessment and system zoning.

Effective cancer treatment requires early detection and monitoring the development progress in a simple and affordable manner. Point-of care (POC) screening can provide a portable and inexpensive tool for the end-users to conveniently operate test and screen their health conditions without the necessity of special skills. Electrochemical methods hold great potential for clinical analysis of variety of chemicals and substances as well as cancer biomarkers due to their low cost, high sensitivity, multiplex detection ability, and miniaturization aptitude. Advances in two-dimensional (2D) material-based electrochemical biosensors/sensors are accelerating the performance of conventional devices toward more practical approaches. Here, recent trends in the development of 2D material-based electrochemical biosensors/sensors, as the next generation of POC cancer screening tools, are summarized. Three cancer biomarker categories, including proteins, nucleic acids, and some small molecules, will be considered. Various 2D materials will be introduced and their biomedical applications and electrochemical properties will be given. The role of 2D materials in improving the performance of electrochemical sensing mechanisms as well as the pros and cons of current sensors as the prospective devices for POC screening will be emphasized. Finally, the future scopes of implementing 2D materials in electrochemical POC cancer diagnostics for the clinical translation will be discussed.

MXene nanosheets of type Ti3C2Tx were modified with β-hydroxybutyrate dehydrogenase and then used as a biosensor for amperometric sensing of β-hydroxybutyrate. The MXene and the nanocomposite were characterized by X-ray photoelectron spectroscopy, field-emission scanning electron microscopy, X-ray diffraction, and Fourier transform infrared spectroscopy. The MXene has a layered structure and proved to be an excellent immobilization matrix providing good compatibility with the enzyme β-hydroxybutyrate dehydrogenase. The MXene-based biosensor, best operated at a potential of − 0.35 V (vs. Ag/AgCl), displays a wide linear range (0.36 to 17.9 mM), a sensitivity of 0.480 μA mM−1 cm−2, and a low detection limit (45 μM). The biosensor was successfully applied to the determination of β-hydroxybutyrate in (spiked) real serum samples. [Figure not available: see fulltext.].

Development of a very sensitive biosensor is accompanied with an inevitable shrinkage in the linear detection range. Here, we developed an electrochemical biosensor with a novel methodology to detect microRNA-21 (miR21) at an ultralow level and broad linear detection range. A three-way junction RNA structure was designed harboring (i) a methylene blue (MB)-modified hairpin structure at its one leg to function as the sensing moiety and (ii) the other two legs to be further hybridized with barcode gold nanoparticles (MB/barG) as the signal amplifiers. Addition of target miR21 resulted in opening the hairpin moiety and subsequent hybridization with DNA-modified gold nanoflower/platinum electrode (GNF@Pt) to form the MB-3 sensor. Inspired by the relay-race run, to extend the dynamic detection range and increase the sensitivity of the biosensor, MB/barG was added to form the second detection modality (MBG-3). The combined sensor required very low sample volume (4 μL) and could identify 135 aM or 324 molecules of miR21 with the ability to operate within a wide linear range from 1 μM down to 500 aM. The fabricated GNF@Pt showed a remarkable conductivity compared with the gold nanoparticle-modified electrode. Addition of MB/barG boosted the electrochemical signal of the MB by almost 230 times. Moreover, a new protocol was introduced by the authors to increase the efficiency of microRNA extraction from the total serum. Possessing a sound selectivity and specificity towards single base-pair mutations, the developed biosensor could profile cancer development stages of two patient serums.

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 (Bi

Immunotherapy is an efficient approach to clinical oncology. However, the immune privilege of the central nervous system (CNS) limits the application of immunotherapeutic strategies for brain cancers, especially glioblastoma (GBM). Tumor resistance to immune checkpoint inhibitors is a further challenge in immunotherapies. To overcome the immunological tolerance of brain tumors, a novel multifunctional nanoparticle (NP) for highly efficient synergetic immunotherapy is reported. The NP contains an anti-PDL1 antibody (aPDL1), upconverting NPs, and the photosensitizer 5-ALA; the surface of the NP is conjugated with the B1R kinin ligand to facilitate transport across the blood-tumor-barrier. Upon irradiation with a 980 nm laser, 5-ALA is transformed into protoporphyrin IX, generating reactive oxygen species. Photodynamic therapy (PDT) further promotes intratumoral infiltration of cytotoxic T lymphocytes and sensitizes tumors to PDL1 blockade therapy. It is demonstrated that combining PDT and aPDL1 can effectively suppress GBM growth in mouse models. The proposed NPs provide a novel and effective strategy for boosting anti-GBM photoimmunotherapy.

The quantification of cancer-derived exosomes has a strong potential for minimally invasive diagnosis of cancer during its initial stage. As cancerous exosomes form a small fraction of all the exosomes present in blood, ultra-sensitive detection is a prerequisite for the development of exosome-based cancer diagnostics. Herein, a detachable microfluidic device implemented with an electrochemical aptasensor (DeMEA) is introduced for highly sensitive and in-situ quantification of cancerous exosomes. To fabricate the aptasensor, a nanocomposite was applied on the electrode surface followed by electroplating of gold nanostructures. Subsequently, an aptamer against an epithelial cell adhesion molecule is immobilized on the electrode surface to specifically detect cancer-specific exosomes. A microfluidic vortexer is then constructed and implemented in the sensing system to increase the collision between the exosomes and sensing surface using hydrodynamically generated transverse flow. The microfluidic vortexer was integrated with the aptasensor via a 3D printed magnetic housing. The detachable clamping of the two different devices provides an opportunity to subsequently harvest the exosomes for downstream analysis. The DeMEA has high sensitivity and specificity with an ultra-low limit of detection of 17 exosomes/μL over a wide dynamic range (1 × 102 to 1 × 109) exosomes/μL in a short period. As proof of the concept, the aptasensor can be separated from the 3D printed housing to harvest and analyze the exosomes by real-time polymerase chain reaction. Moreover, the DeMEA quantifies the exosomes from plasma samples of patients with breast cancer at different stages of the disease. The DeMEA provides a bright horizon for the application of microfluidic integrated biosensors for the early detection of cancerous biomarkers.

It is known that tumor antigens could induce obvious anti-tumor immune responses for efficient cancer immunotherapy when combined with checkpoint blockade. However, the amount of tumor antigens is often limited due to the suppressive tumor microenvironment (TME). Here, a new type of nanomaterial was developed to improve tumor treatment by the combined action of starving therapy/photodynamic therapy (PDT)/photothermal therapy (PTT) and checkpoint-blockade immunotherapy. In detail, the immunoadjuvant nanoagents (γ-PGA@GOx@Mn,Cu-CDs) were fabricated by integrating the gamma-glutamyl transferase (GGT) enzyme-induced cellular uptake polymer-poly (γ-glutamic acid) (γ-PGA), a glucose-metabolic reaction agent - glucose oxidase (GOx), Mn,Cu-doped carbon dots (CDs) as photosensitizer and self-supplied oxygenator nanodots. γ-PGA@GOx@Mn,Cu-CDs nanoparticles (NPs) showed long retention time at the tumor acidic microenvironment and could further target cancer cells. The NPs also displayed both photothermal and photodynamic effects under laser irradiation at 730 nm. Interestingly, the endogenous generation of hydrogen peroxide (H2O2) caused by the nanoreactors could significantly relieve tumor hypoxia and further enhance in vivo PDT. By synergistically combining the NPs-based starving-like therapy/PDT/PTT and check-point-blockade therapy, the treatment efficiency was significantly improved. More importantly, the systematic antitumor immune response would eliminate non-irradiated tumors as well, which is promising for metastasis inhibition.

Multiple and sensitive detection of oncomiRs for accurate cancer diagnostics is still a challenge. Here, a synergetic amplification strategy was introduced by combining a MXene-based electrochemical signal amplification and a duplex-specific nuclease (DSN)-based amplification system for rapid, attomolar and concurrent quantification of multiple microRNAs on a single platform in total plasma. Synthesized MXene-Ti3C2Tx modified with 5 nm gold nanoparticles (AuNPs) was tasted on a dual screen-printed gold electrode to host vast numbers of DNA probes identically co-immobilized on dedicated electrodes. Interestingly, presence of MXene provided biofouling resistance and enhanced the electrochemical signals by almost 4 folds of magnitude, attributed to its specious surface area and remarkable charge mobility. The 5 nm AuNPs were perfectly distributed within the whole flaky architect of the MXene to give rise to the electrochemical performance of MXene and provide the thiol-Au bonding feature. This synergetic strategy reduced the DSN-based biosensors' assay time to 80 min, provided multiplexability, antifouling activity, substantial sensitivity and specificity (single mutation recognition). The limit of detection of the proposed biosensor for microRNA-21 and microRNA-141 was respectively 204 aM and 138 aM with a wide linear range from 500 aM to 50 nM. As a proof of concept, this newly-developed strategy was coupled with a 96-well adaptive sensing device to successfully profile three cancer plasma samples based on their altered oncomiR abundances.

In article number https://doi.org/10.1002/advs.201902477, Peixuan Guo, Jeong‐Woo Choi, and co‐workers fabricate monofunctionalized gold nanoparticles (AuNPs) with a single copy of an RNA three‐way junction (3WJ) motif for application in ultra‐sensitive miRNA biosensing using electrochemical surface‐enhanced Raman spectroscopy (EC‐SERS). In the presence of miRNA‐155, miRNA‐155 displaces the 3WJ structure and it results in a remarkable increase in the electrochemical and SERS signals.

The field of bioelectronics has paved the way for the development of biochips, biomedical devices, biosensors and biocomputation devices. Various biosensors and biomedical devices have been developed to commercialize laboratory products and transform them into industry products in the clinical, pharmaceutical, environmental fields. Recently, the electrochemical bioelectronic devices that mimicked the functionality of living organisms in nature were applied to the use of bioelectronics device and biosensors. In particular, the electrochemical-based bioelectronic devices and biosensors composed of biomolecule-nanoparticle hybrids have been proposed to generate new functionality as alternatives to silicon-based electronic computation devices, such as information storage, process, computations and detection. In this chapter, we described the recent progress of bioelectronic devices and biosensors based on biomaterial-nanomaterial hybrid.

For the first time, topological insulator bismuth selenide nanoparticles (Bi

The field of bioelectronics has paved the way for the development of biochips, biomedical devices, biosensors and biocomputation devices. Various biosensors and biomedical devices have been developed to commercialize laboratory products and transform them into industry products in the clinical, pharmaceutical, environmental fields. Recently, the electrochemical bioelectronic devices that mimicked the functionality of living organisms in nature were applied to the use of bioelectronics device and biosensors. In particular, the electrochemical-based bioelectronic devices and biosensors composed of biomolecule-nanoparticle hybrids have been proposed to generate new functionality as alternatives to silicon-based electronic computation devices, such as information storage, process, computations and detection. In this chapter, we described the recent progress of bioelectronic devices and biosensors based on biomaterial-nanomaterial hybrid.

A newly developed electrochemical biosensor composed of a topological insulator (TI) and metallic DNA (mDNA) is fabricated. The bismuth selenide nanoparticle (Bi

In the present work, hard anodization assisted by anode temperature ramp was employed to fabricate self-ordered nanoporous alumina in the wide range of interpore distances (259–405 nm) in pure oxalic acid and mixture of oxalic and phosphoric acid solutions. Anode temperature ramp technique was employed to adjust the anodization current density to optimize the self-ordering of the nanopore arrays in the interpore range in which no ordered self-assembled hard anodized anodic aluminum oxide has reported. It is found that the certain ratios of oxalic and phosphoric acid solutions in this anodization technique increased self-ordering of the nanopores especially for anodization voltages over the 170 V by increasing alumina’s viscous flow which could lead to decrease the overall current density of anodization, yet leveled up by anode temperature ramp. However, below 150 V anodization voltage, the ratio of interpore distance to the anodization voltage of the both anodization techniques was the same (~2 nm/V), while above this voltage, it increased to about 2.2 nm/V.

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.

A newly developed electrochemical biosensor composed of a topological insulator (TI) and metallic DNA (mDNA) is fabricated. The bismuth selenide nanoparticle (Bi2 Se3 NP) is synthesized and sandwiched between the gold electrode and another Au-deposited thin layer (Bi2 Se3 @Au). Then, eight-silver-ion mediated double-stranded DNA (mDNA) is immobilized onto the substrate (Bi2 Se3 @Au-mDNA) for the further detection of hydrogen peroxide. The Bi2 Se3 NP acts as the electrochemical-signal booster, while unprecedentedly its encapsulation by the Au thin layer keeps the TI surface states protected, improves its electrochemical-signal stability and provides an excellent platform for the subsequent covalent immobilization of the mDNA through Au-thiol interaction. Electrochemical results show that the fabricated biosensor represents much higher Ag+ redox current (≈10 times) than those electrodes prepared without Bi2 Se3 @Au. The characterization of the Bi2 Se3 @Au-mDNA film is confirmed by atomic force microscopy, scanning tunneling microscopy, and cyclic voltammetry. The proposed biosensor shows a dynamic range of 00.10 × 10-6 m to 27.30 × 10-6 m, very low detection limit (10 × 10-9 m), unique current response (1.6 s), sound H2 O2 recovery in serum, and substantial capability to classify two breast cancer subtypes (MCF-7 and MDA-MB-231) based on their difference in the H2 O2 generation, offering potential applications in the biomedicine and pharmacology fields.

High field accelerated mild anodization was used to fabricate self-ordered nanoporous alumina arrays. The phosphoric acid with various concentrations was used in a wide range of anodization voltages. Two different temperatures for both sides of the samples were employed to maintain a mid level of current density during the anodization process. The interpore distances were seen to vary from 300 to 400 nm when the anodization voltages changed from 150 to 190 V. A nonlinear-inverse relation between electrolyte concentrations of phosphoric acid and anodization voltages was found in the optimum self-ordering conditions. Similar to the hard anodization, the ratio of interpore distance to voltage was 2 nm/V in high field accelerated mild anodization technique.

The invention relates to a solution for detection of a viral RNA sequence the solution comprising a double stranded (duplex) initiation helix, at least one signal system, and at least two probes A and B having hairpin structures. The invention further relates to a kit comprising said solution, and the use of said solution for e.g. detection of viral RNA in a sample.

Terminal deoxynucleotidyl transferase (TdT) enzyme plays an integral part in the V(D)J recombination, allowing for the huge diversity in expression of immunoglobulins and T-cell receptors within lymphocytes, through their unique ability to incorporate single nucleotides into oligonucleotides without the need of a template. The role played by TdT in lymphocytes precursors found in early vertebrates is not known. In this paper, we demonstrated a new screening method that utilises TdT to form libraries of variable sized (vsDNA) libraries of polynucleotides that displayed binding towards protein targets. The extent of binding and size distribution of each vsDNA library towards their respective protein target can be controlled through the alteration of different reaction conditions such as time of reaction, nucleotide ratio and initiator concentration raising the possibility for the rational design of aptamers prior to screening. The new approach, allows for the screening of aptamers based on size as well as sequence in a single round, which minimises PCR bias. We converted the protein bound sequences to dsDNA using rapid amplification of variable ends assays (RAVE) and sequenced them using next generation sequencing. The resultant aptamers demonstrated low nanomolar binding and high selectivity towards their respective targets.