Methylene Blue-Stained Single-Stranded DNA Aptamers as a Highly Efficient Electronic Switch for Quasi-Reagentless Exosomes Detection: An Old Dog with New Tricks.

Improving the convenience, sensitivity, and cost-effectiveness of electrochemical biosensors is crucial for advancing their clinical diagnostic applications. Herein, we presented an elegant approach to construct electrochemical aptasensors for tumor-derived exosome detection by harnessing the alterable interaction between methylene blue (MB) and DNA aptamer. In detail, the anti-EpCAM aptamer, named SYL3C, was found to exhibit a strong affinity toward MB due to the specific interaction between MB and unbound guanine bases. Thereby, SYL3C could be stained with MB to arouse a strong electrochemical signal on a gold electrode (AuE). Upon binding to EpCAM-positive exosomes, SYL3C underwent a conformational transformation. The resulting conformation, or exosomes-SYL3C complex, not only reduced the accumulation of MB on SYL3C by obstructing the accessibility of guanines to MB but also impeded the transfer of electrons from the bound MB to AuE, leading to a notable decrease in the electrochemical signal. Using MB-stained SYL3C as an electronic switch, an electrochemical aptasensor was readily established for the detection of EpCAM-positive exosome detection. Without the need for signal amplification strategies, expensive auxiliary reagents, and complex operation, this unique signal transduction mechanism alone could endow the aptasensor with ultrahigh sensitivity. A limit of detection (LOD) of 234 particles mL-1 was achieved, surpassing the performance of most reported methods. As a proof of concept, the aptasensor was applied to analyze clinical serum samples and effectively distinguish non-small-cell lung cancer (NSCLC) patients from healthy individuals. As EpCAM exhibits broad expression in exosomes derived from different tumor sources, the developed aptasensor holds promise for diagnosing other tumor types.

B7H3 targeting gold nanocage pH-sensitive conjugates for precise and synergistic chemo-photothermal therapy against NSCLC.

BACKGROUND: The combination of drug delivery with immune checkpoint targeting has been extensively studied in cancer therapy. However, the clinical benefit for patients from this strategy is still limited. B7 homolog 3 protein (B7-H3), also known as CD276 (B7-H3/CD276), is a promising therapeutic target for anti-cancer treatment. It is widely overexpressed on the surface of malignant cells and tumor vasculature, and its overexpression is associated with poor prognosis. Herein, we report B7H3 targeting doxorubicin (Dox)-conjugated gold nanocages (B7H3/Dox@GNCs) with pH-responsive drug release as a selective, precise, and synergistic chemotherapy-photothermal therapy agent against non-small-cell lung cancer (NSCLC). RESULTS: In vitro, B7H3/Dox@GNCs exhibited a responsive release of Dox in the tumor acidic microenvironment. We also demonstrated enhanced intracellular uptake, induced cell cycle arrest, and increased apoptosis in B7H3 overexpressing NSCLC cells. In xenograft tumor models, B7H3/Dox@GNCs exhibited tumor tissue targeting and sustained drug release in response to the acidic environment. Wherein they synchronously destroyed B7H3 positive tumor cells, tumor-associated vasculature, and stromal fibroblasts. CONCLUSION: This study presents a dual-compartment targeted B7H3 multifunctional gold conjugate system that can precisely control Dox exposure in a spatio-temporal manner without evident toxicity and suggests a general strategy for synergistic therapy against NSCLC.

Codelivery of dihydroartemisinin and chlorin e6 by copolymer nanoparticles enables boosting photodynamic therapy of breast cancer with low-power irradiation.

Given that chemotherapy as a stand-alone therapeutic strategy may not be sufficient to effectively treat cancer, there is increasing interest in combination of chemotherapy and alternative therapies. Photodynamic therapy has the advantages of high selectivity and low side effects, so the combination of photodynamic therapy and chemotherapy has become one of the most appealing strategies for tumor treatment. In this work, we constructed a nano drug codelivery system (PPDC) to realize the combined treatment of chemotherapy and photodynamic therapy through encapsulating chemotherapeutic drug dihydroartemisinin and photosensitizer chlorin e6 in PEG-PCL. The potentials, particle size and morphology of nanoparticles were characterized by dynamic light scattering and transmission electron microscopy. We also investigated the reactive oxygen species (ROS) generation and drug release ability. The antitumor effect in vitro was investigated by methylthiazolyldiphenyl-tetrazolium bromide assays and cell apoptosis experiments, and the potential cell death mechanisms were explored by ROS detection and Western blot analysis. The in vivo antitumor effect of PPDC was evaluated under the guidance of fluorescence imaging. Our work provides a potential antitumor treatment approach and expands the application of dihydroartemisinin for breast cancer therapy.

Exploiting the size exclusion effect of protein adsorption layers for electrochemical detection of microRNA: A new mechanism for design of E-DNA sensor.

The assay performance of electrochemical DNA (E-DNA) sensors is deeply influenced by the state of DNA probes immobilized on electrode. Moreover, the immobilization procedures for DNA probes are tedious and vary according to the probes and analytes. In this work, we find that the adsorption layers of bovine serum albumin (BSA) on gold electrode (AuE) possess a size exclusion effect to distinguish between single-stranded (-ss) DNA probes and the DNA fragments generated from enzymatic digestion of ssDNA probes. In detail, the BSA layers act as a gatekeeper that hinders the adsorption of a ssDNA probe on AuE but permits the DNA fragments with much smaller sizes to pass through the adsorption layers and adsorb on AuE. This finding is developed into a novel E-DNA sensor for microRNA (miRNA) detection by coupling with duplex-specific nuclease (DSN)-assisted target recycling strategy. The ssDNA probe in solution phase is enzymatically digested during the DSN-assisted target recycling process initiated by target miRNA-21, generating plenty of DNA fragments. The adsorption of these DNA fragment on BSA/AuE is permitted, which arouses electrochemical signals after binding with [Ru(NH3)6]3+ to indicate the recognition of miRNA-21. The developed E-DNA sensor possesses a wide calibration range from 0.001 to 100 pM and a low detection limit of 0.48 fM. Significantly, accurate evaluation of miRNA-21 expression levels in cancer cell lines and non-small-cell lung carcinomas (NSCLC) serum samples are successfully achieved using the developed method. This work provides a new mechanism for constructing sensitive E-DNA sensor without tedious probe immobilization procedures.

Colorimetric and photothermal dual-mode immunoassay of aflatoxin B1 based on peroxidase-like activity of Pt supported on nitrogen-doped carbon.

In this work, a split-type dual-mode (colorimetric/photothermal) immunoassay method was designed for point-of-care testing (POCT) detection of mycotoxins (aflatoxin B1, AFB1 as the model analyte) in foodstuffs based on Pt supported on nitrogen-doped carbon amorphous (Pt-CN). The as-synthesized Pt-CN exhibits excellent peroxidase-mimicking activity, which can catalyze the oxidization of 3,3',5,5'-tetramethylbenzidine (TMB) into TMBox with sensitive colorimetric readout in the presence of hydrogen peroxide (H2O2). Moreover, the TMBox also serves as a near-infrared (NIR) photothermal agent to convert the colorimetric readout into heat under the irradiation of an 808 nm laser. A competitive-type immunoreaction is carried out between AFB1 and glucose oxidase (GOx)-labeled AFB1-bovine serum albumin (AFB1-BSA-GOx) conjugates. With the formation of immune complexes, the entrained GOx catalyzes the hydrolysis of glucose to generate H2O2, which further involves the Pt-CN catalyzed production of TMBox to increase colorimetric/photothermal readouts. Depending on the degree of TMB oxidation, the dual-mode immunoassay provides a linear range of 1.0 pg/mL to 10 ng/mL, with a limit of detection (LOD) of 0.22 pg/mL for the colorimetric assay and 0.76 pg/mL for the photothermal assay. Moreover, the developed method is successfully used to detect AFB1 in peanuts with acceptable accuracy compared with commercially enzyme-linked immunosorbent assay (ELISA) kits. Significantly, the photothermal readout in this method is recorded on a mobile phone device without any expensive instruments, providing an affordable and convenient tool for food safety testing.

Co-Delivery of Dihydroartemisinin and Indocyanine Green by Metal-Organic Framework-Based Vehicles for Combination Treatment of Hepatic Carcinoma.

Dihydroartemisinin (DHA), a widely used antimalarial agent, has clinical potential for the treatment of hepatic carcinoma. Although chemotherapy is indispensable for tumor therapy, it is generally limited by poor solubility, low efficiency, rapid clearance, and side effects. As an emerging treatment method, photothermal therapy (PTT) has many outstanding properties, but suffers from poor photostability of photosensitizer and incomplete ablation. Multimodal therapies could combine the advantages of different therapy methods to improve antitumor efficiency. Hence, we designed a nano-delivery system (ICG&DHA@ZIF-8) using zeolitic imidazolate framework-8 (ZIF-8) with a high porous rate and pH sensitivity property, to co-load DHA and indocyanine green (ICG). Dynamic light scattering and transmission electron microscopy were used to characterize the prepared nanoparticles. The photothermal conversion and drug release performances of ICG&DHA@ZIF-8 were investigated. In vitro antitumor efficacy and cellular uptake were studied. The mechanism of the combination treatment was studied by reactive oxygen species level detection and western blot assays. In vivo antitumor assays were then studied with the guidance of ex vivo imaging. The results showed that the ICG&DHA@ZIF-8 based combination therapy could efficiently kill hepatic carcinoma cells and suppress tumor growth. This research provides a potential nanodrug for the treatment of hepatic carcinoma.

Enhanced Cancer Starvation Therapy Enabled by an Autophagy Inhibitors-Encapsulated Biomimetic ZIF-8 Nanodrug: Disrupting and Harnessing Dual Pro-Survival Autophagic Responses.

Autophagy is an important protective mechanism in maintaining or restoring cell homeostasis under physiological and pathological conditions. Nanoparticles (NPs) with certain components and morphologies can induce autophagic responses in cancer cells, providing a new perspective for establishing cancer therapy strategies. Herein, a novel nanodrug system, cell membranes-coated zeolitic imidazolate framework-8 (ZIF-8) NPs encapsulating chloroquine (CQ) and glucose oxidase (GOx) (defined as mCG@ZIF), is designed to achieve an enhanced anticancer effect with the combination of starvation therapy and an autophagy regulation strategy. It is found that ZIF-8 as a nanocarrier can induce autophagy to promote survival of cancer cells via the upstream Zn2+-stimulated mitochondrial reactive oxygen species (ROS) so that the anticancer effect is directly achieved by inhibiting this pro-survival autophagy using CQ released from mCG@ZIF under a tumor acidic microenvironment. Moreover, a cancer cell under starvation caused by GOx harnesses autophagy to maintain intracellular ATP levels and resist starvation therapy. The released CQ further inhibits the starvation-induced pro-survival autophagy and cuts off the protective pathway of cancer cells, enhancing the anticancer efficiency of GOx-based starvation therapy. Significantly, the cell membrane coating endows mCG@ZIF with excellent in vivo homotypic targeting ability. Both in vitro and in vivo results have confirmed the enhanced anticancer effect achieved by mCG@ZIF with a negligible side effect.

Enzyme-controllable just-in-time production system of copper hexacyanoferrate nanoparticles with oxidase-mimicking activity for highly sensitive colorimetric immunoassay.

Nanozymes are a series of elaborately designed nanomaterials that can mimic the catalytic sites of natural enzymes for reactions. Bypassing the tedious design and preparation of nanomaterial, in this work, we report on a novel just-in-time production system of copper hexacyanoferrate nanoparticles (CHNPs), which act as an oxidase-mimicking nanozyme. This system can rapidly produce CHNPs nanozyme on demand by simply mixing Cu(II) with potassium hexacyanoferrate(III) (K3[Fe(CN)6]). It is found that once K3[Fe(CN)6] is reduced to K4[Fe(CN)6], the formation of CHNPs is inhibited. Therefore, the just-in-time production system of CHNPs was coupled with alkaline phosphatase (ALP) to construct an enzyme-controllable just-in-time production (ECJP) system, in which ALP could inhibit the production of by catalyzing the hydrolysis of ascorbic acid 2-phosphate (AAP) to generating ascorbic acid (AA). The ECJP system is then used to probe the activity of ALP by employing 2,2'-azinobis-(3-ethylbenzthiazoline-6-sulphonate) (ABTS) as the chromogenic substrate, and a detection limit of 0.003 U L-1 was achieved. Moreover, by adapting ALP as the enzyme label, an ECJP system-based colorimetric immunoassay protocol was established for sensitive detection of aflatoxin B1 (AFB1), and a detection limit as low as 0.73 pg mL-1 was achieved. The developed immunoassay method is successfully applied to the detection of AFB1 in peanut samples. The operation of ECJP system is quite simple and the coupling of ALP with CHNPs nanozyme can arouse dual enzyme-like cascade signal amplification. So, we believe this work can offer a new perspective for the development of nanozymes-based biodetection methods and colorimetric immunoassay strategies.

Biocatalysis-mediated MOF-to-prussian blue transformation enabling sensitive detection of NSCLC-associated miRNAs with dual-readout signals.

Sensitive and accurate miRNAs assay is critical for early diagnosis of non-small-cell lung carcinomas (NSCLC). Herein, we demonstrate a photothermal and electrochemical dual-readout assay method for miRNA detection based on a novel biocatalysis-mediated MOF-to-prussian blue (PB) transformation (BMMPT) strategy and the catalytic hairpin assembly (CHA) amplification strategy. It is found that the Fe2+-based MOF (MOF-Fe2+) can act as the Fe2+ source to react with K3[Fe(CN)6], leading to the in-situ formation of prussian blue (PB) on MOF-Fe2+. Due the inherent near-infrared (NIR) photothermal conversion ability and electrochemical signal of PB, the resulting PB@MOF-Fe2+ is employed to arouse temperature readout or electrochemical signal. The presence of target miRNA-21 triggers the CHA reaction on magnetic beads (MBs), resulting the capture of numerous glucose oxidase (GOx) tags on MBs. The GOx tags then catalyze the generation of H2O2 using glucose as substrate. The H2O2 is used to inhibit the MOF-to-PB transformation process by oxidizing Fe2+ into Fe3+, leading to the decrease in temperature and electrochemical readout aroused by PB@MOF-Fe2+. By this means, a signal-off assay mode with dual readout is established for miRNA-21. Under the optimal conditions, using temperature readout or electrochemical readout, miRNA-21 can be detected at concentrations as low as 0.3 fM and 0.32 fM, respectively. Moreover, the developed method is successfully applied to evaluate the expression level of miRNA-21 in serum of NSCLC patients. This work not only provides a practical tool for NSCLC diagnosis but also presents the new features of MOF materials as signal transduction tags.

Dual biomineralized metal-organic frameworks-mediated conversion of chemical energy to electricity enabling portable PEC sensing of telomerase activity in bladder cancer tissues.

In this work, we report on a portable photoelectrochemical (PEC) sensing system for telomerase activity detection based on dual biomineralized ZIF-8 nanoparticles (NPs)-medicated conversion of chemical energy to electricity and terminal deoxynucleoside transferase (TdTase)-catalyzed elongation of Y-junction DNA structure. Two kinds of biomineralized ZIF-8 NPs including glucose oxidase (GOx)-encapsulated ZIF-8 (GZIF) and horseradish peroxidase (HRP)-encapsulated ZIF-8 (HZIF) are involved in this assay system. The recognition of telomerase is started with telomerase-catalyzed elongation of a telomerase substrate (TS) primer, which generates a longer elongation chain to trigger the formation of a Y-junction DNA structure. The Y-junction DNA with abundant 3'-OH terminal and small steric hindrance facilitates the implement of TdTase-catalyzed elongation reaction, in which the branches of Y-junction DNA are elongated and endowed with biotin moiety to capture streptavidin-modified GZIF (SA-GZIF). The signal transduction is then achieved on a luminol/HZIF/CdS-based photoelectrode. Once the H2O2 produced from GZIF-catalyzed hydrolysis of glucose is introduced to the photoelectrode, chemiluminescence of HRP-luminol-H2O2-p-iodo-phenol (PIP) system confined in HZIF is activated to excite photocurrent of CdS NPs, which is then recorded by a portable digital multimeter (DMM). The developed PEC sensing system possesses a wide calibration range from 50 to 5000 HeLa cells and a low detection limit of 46 cells. Significantly, the sensing platform is successfully applied to evaluate the telomerase activity in resected bladder tumor tissues. This work not only provides a diagnostic tool for telomerase-related diseases but also open a new avenue for establishing PEC assay methods using metal-organic framework (MOF) NPs.

Nanoscale assembly line composed of dual DNA-machines enabling sensitive microRNA detection using upconversion nanoparticles probes.

DNA machines are smart artificial devices that perform well-organized DNA hybridization reactions or nanoscale mechanical movements. Herein, a nanoscale assembly line composing of dual DNA machines is meticulously designed by coupling a catalytic hairpin assembly (CHA)-based machine with a 3D DNA walker machine. Equipped with upconversion nanoparticles (UCNPs) as signal tags, the dual DNA machines-based assembly line (DDMAL) can efficiently amplify the fluorescent signal of target recognition event, enabling sensitive detection of microRNA (miRNA). In detail, once activated by target miRNA-21, the CHA machine is initiated to constantly produce a single-stranded DNA (named binding DNA) via the strand displacement reaction. The binding DNA as a trigger factor can initiate the DNA walker machine by linking a walking strand DNA with an anchor strand DNA immobilized on the surface of magnetic beads (MBs). The movement of walking strand on the surface of MBs is then driven by Mn2+-dependent DNAzyme formed through the hybridization of walking strand with a UCNPs-linked substrate strand. The DNAzyme-catalyzed cleavage of substrate strand is accompanied by the release of numerous UCNPs from MBs. By measuring the fluorescent signal of released UCNPs after the magnetic separation, target miRNA-21 can be detected by the DDMAL system in a linear range from 1.0 fM to 10 nM, with a limit of detection (LOD) of 0.62 fM (3σ). Moreover, the practicability of DDMAL system was demonstrated by using it to evaluate the expression levels of miRNA-21 in cell lines and assay miRNA-21 in human serum.

Polymerization-driven successive collapse of DNA dominoes enabling highly sensitive cancer gene diagnosis.

We propose a novel fluorescence assay method by designing a polymerization-driven DNA dominoes collapse (PDDC) strategy, enabling highly sensitive detection of p53 gene (as a model analyte) and single nucleotide polymorphism analysis.

A three-dimensional DNA walker amplified FRET sensor for detection of telomerase activity based on the MnO2 nanosheet-upconversion nanoparticle sensing platform.

A novel fluorescent sensing platform for telomerase activity assay was developed by coupling a three-dimensional (3D) DNA walker with the MnO2 nanosheet-upconversion nanoparticle (UCNPs) complex-based fluorescence resonance energy-transfer (FRET) system.

Nonenzymatic sensing of hydrogen peroxide using a glassy carbon electrode modified with graphene oxide, a polyamidoamine dendrimer, and with polyaniline deposited by the Fenton reaction.

A highly sensitive electrochemical sensor is described for the determination of H2O2. It is based on based on the use of polyaniline that was generated in-situ and within 1 min on a glassy carbon electrode (GCE) with the aid of the Fe(II)/H2O2 system. Initially, a 2-dimensional composite was prepared from graphene oxide and polyamidoamine dendrimer through covalent interaction. It was employed as a carrier for Fe(II) ions. Then, the nanocomposite was drop-coated onto the surface of the GCE. When exposed to H2O2, the Fe(II) on the GCE is converted to Fe(III), and free hydroxy radicals are formed. The Fe(III) ions and the hydroxy radicals catalyze the oxidation of aniline to produce electroactive polyaniline on the GCE. The resulting sensor, best operated at a working potential as low as 50 mV (vs. SCE) which excludes interference by dissolved oxygen, has a linear response in the 500 nM to 2 mM H2O2 concentration range, and the detection limit is 180 nM. The sensor was successfully applied to the determination of H2O2 in spiked milk and fetal bovine serum samples. Graphical abstract Schematic presentation of a sensitive electrochemical sensor employed for detection of H2O2 in sophisticated matrices by using graphene oxide-PAMAM dendrimer as initiator container and Fe2+/H2O2 system as signal enhancer.

Protein-templated Fe2O3 microspheres for highly sensitive amperometric detection of dopamine.

The authors describe an amperometric sensor for dopamine (DA) by employing olive-like Fe2O3 microspheres (OFMs) as the electrocatalyst for DA oxidization. The OFMs were prepared by using a protein templated method. The structure and properties of the OFMs were characterized by scanning electron microscopy, X-ray powder diffraction, energy dispersive x-ray spectroscopy, cyclic voltammetry and electrochemical impedance spectroscopy. The OFMs possess excellent catalytic activity towards DA oxidization due to their unique morphology. The sensor responds to DA within less than 5 s. The sensor, best operated at a voltage of +0.2 V (vs. SCE) responds linearly in the 0.2 to 115 µM DA concentration range and has a 30 nM detection limit. The selectivity, reproducibility and long-term stability of the sensor are acceptable. It performs well when applied to spiked human urine samples. Graphical abstract Olive-like Fe2O3 microspheres (OFMs), synthesized using egg white as template, display excellent catalytic activity towards dopamine (DA) oxidization due to their unique morphology. They were applied for DA detection using the amperometric technique. The electrochemical sensor exhibited a high sensitivity and a 30 nM detection limit. DAQ: dopaquinone.

Two-dimensional MoS2 as a nano-binder for ssDNA: Ultrasensitive aptamer based amperometric detection of Ochratoxin A.

Two-dimensional (2D) MoS2 is found to possess different affinities for ssDNA and dsDNA. This finding is exploited in an amperometric aptamer-based method for the determination of the mycotoxin ochratoxin A (OTA). Initially, a dsDNA probe (formatted through the hybridization of OTA-aptamer with an auxiliary DNA) is self-assembled on a gold electrode. Upon introduction of OTA, it will bind to the aptamer and cause the unwinding of dsDNA, while the auxiliary DNA (with single-stranded structure) remains on the electrode. Since the affinity of 2D MoS2 for ssDNA is considerably larger than that for dsDNA, it will be adsorbed on the electrode by binding to the auxiliary DNA. Notably, 2D MoS2 possesses peroxidase-like activity. Hence, it can catalyze the amplification of electrochemical signal of the hydroquinone/benzoquinone redox system. Under optimal conditions, the amperometric signal (best measured at -0.2 V vs. SCE) increases with increasing OTA concentration in the range from 0.5 pg·mL-1 to 1.0 ng·mL-1, with a lower detection limit of 0.23 pg·mL-1. The method was applied to the determination of OTA in spiked red wine. Graphical abstract Herein we construct a convenient electrochemical aptasensor for sensitive monitor of ochratoxin A by using 2D MoS2 as a nano-binder to catalyze the amplification of electrochemical signal from hydroquinone/benzoquinone system.

Liposome-amplified photoelectrochemical immunoassay for highly sensitive monitoring of disease biomarkers based on a split-type strategy.

Liposomes are an excellent candidate component for biosensors to transduce and amplify detection signals due to their outstanding ability in encapsulating signal marker compounds. However, the use of liposomes for photoelectrochemical (PEC) signal transduction has not yet been achieved due the lack of appropriate sensing strategy. Herein, we report on a novel liposomes-amplified PEC immunoassay (LAPIA) method for sensitive HIV-p24 antigen (p24) detection based on a split-type strategy. Initially, liposomes were encapsulated with alkaline phosphatase (ALP) in their hydrophilic chamber and conjugated with secondary antibody on the surface to form the ALP-encapsulated liposomes (ALP-Ls) based PEC signal label. Sandwiched immunoassay based on the ALP-Ls label was then carried out in microwell plate. Upon addition of tween 20, the ALP molecules were released and catalyzed the hydrolysis of ascorbic acid 2-phosphate (AA-p) to produce ascorbic acid (AA). The latter then donated electron to the graphene/g-C3N4 nanohybrids based photoelectrode, arousing an increased photocurrent signal. The separation of immunoreaction step and PEC signal excitation (i.e. split-type) not only enabled the realization of liposomes based amplification strategy, but also could eliminate the PEC-caused biomolecules damage. The developed PEC method possessed a wide calibration range from 1.0pgmL-1 to 50ngmL-1 and a low detection limit of 0.63pgmL-1. Its practicability was demonstrated by assaying human serum samples. Moreover, the universality of the liposomes-amplified PEC sensing strategy was also demonstrated by developing it into a sensitive microRNA detection method.

Strong Near-Infrared Absorbing and Biocompatible CuS Nanoparticles for Rapid and Efficient Photothermal Ablation of Gram-Positive and -Negative Bacteria.

Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli) are the most common infectious bacteria in our daily life, and seriously affect human's health. Because of the frequent and extensive use of antibiotics, the microbial strains forming drug resistance have become more and more difficult to deal with. Herein, we utilized bovine serum albumin (BSA) as the template to synthesize uniform copper sulfide (CuS) nanoparticles via a biomineralization method. The as-prepared BSA-CuS nanocomposites showed good biocompatibility and strong near-infrared absorbance performance and can be used as an efficient photothermal conversion agent for pathogenic bacteria ablation with a 980 nm laser at a low power density of 1.59 W/cm2. The cytotoxicity of BSA-CuS nanocomposite was investigated using skin fibroblast cells and displayed good biocompatibility. Furthermore, the antibacterial tests indicated that BSA-CuS nanocomposite showed no antibacterial activity without NIR irradiation. In contrast, they demonstrated satisfying killing bacterial ability in the presence of NIR irradiation. Interestingly, S. aureus and E. coli showed various antibacterial mechanisms, possibly because of the different architectures of bacterial walls. Considering the low cost, easy preparation, excellent biocompatibility and strong photothermal convention efficiency (24.68%), the BSA-CuS nanocomposites combined with NIR irradiation will shed bright light on the treatment of antibiotic-resistant pathogenic bacteria.

Protein-directed gold nanoparticles with excellent catalytic activity for 4-nitrophenol reduction.

To explore high-performance noble metal nanomaterials for the reduction of the biotoxin 4-nitrophenol (4-NP) in medicine, we developed a green synthesis strategy of bovine serum albumin-stabilized Au nanoparticles (Au@BSA NPs). The as-synthesized Au@BSA NPs were characterized by ultraviolet-visible absorption spectrum, fourier transformed infrared spectroscopy, transmission electron microscopy and dynamic light scattering. The functional bio-nanocomposites showed Au-protein core-shell structure and uniform distribution, and their sizes were dependent on the additive amount of HAuCl4. Interestingly, Au@BSA NPs showed remarkable catalytic activity for the reduction of 4-NP into 4-aminophenol in the presence of sodium borohydride. Due to the introduction of Au@BSA NPs, the reduction reaction could be conducted at ambient temperature and pressure without any additional conditions. Moreover, the reduction rate was closely related to the sizes of NPs and reaction temperature, and the catalytic mechanism was verified to follow the pseudo-first-order kinetics. Due to the environmentally friendly synthesis process and green reduction strategy of 4-NP, Au@BSA NPs would show great potential in governance of the biotoxin in medicine.

Eggshell membrane-templated synthesis of 3D hierarchical porous Au networks for electrochemical nonenzymatic glucose sensor.

Sensitive and accurate test of blood glucose levels is necessary to monitor and prevent diabetic complications. Herein, we developed a novel and sensitive non-enzymatic glucose sensing platform by employing 3D hierarchical porous Au networks (HPANs) as electrocatalyst for glucose oxidization. The HPANs were prepared through a bio-inspired synthesis method, in which the natural eggshell membrane (ESM) was introduced as template. The structure and properties of the as-prepared HPANs were characterized by a set of techniques, including scanning electron microscope (SEM), energy-dispersive X-ray spectroscopy (EDS), powder X-ray diffraction (XRD) and cyclic voltammetry (CV). The HPANs showed high catalytic activity towards glucose oxidization due to the unique structure. Inspiringly, the HPANs-based electrochemical glucose sensor could be driven at low potential (+0.1V) and showed an outstanding performance for glucose determination with two linear ranges of 1-500µM and 4.0-12mM, a limit of detection (LOD) of 0.2µM (3σ), and fast response time (less than 2s). Moreover, the stability and anti-interference performance of developed sensor was also excellent, enabling its preliminary application in clinical sample (human serum) test. Significantly, this work offered an environmentally friendly method for fabricating 3D nanostructure by using ESM (a biowaste) as template, setting up a typical example for producing new value-added nanomaterials with sensing application.