A label-free electrochemical aptasensor based on Bi-Sb alloy materials for potential POCT of HER-2.

As a prognostic biomarker for breast cancer, human epidermal growth factor receptor 2 (HER-2) is of crucial diagnostic value. Here, a label-free electrochemical aptasensor was established for the ultrasensitive detection of HER-2 using a modified electrode of Bi-Sb alloy materials (Bi-Sb AMs). The performance of the aptasensor was enhanced greatly due to the introduction of Bi-Sb alloy materials (Bi-Sb AMs) with high conductivity. Furthermore, by integrating the aptasensor with the Sensit Smart U-disk electrochemical analyzer, the point-of-care testing (POCT) for HER-2 was realized. Under the optimal experimental parameters, the POCT analyzer showed a wide linear response from 0.01 pg mL-1 to 100 ng mL-1, with a low detection limit (LOD) of 5.96 fg mL-1 for the detection of HER-2. The presented POCT analyzer exhibited good specificity, stability, and reproducibility. Benefiting from the simple operation and rapid testing, the developed analyzer will have potential application in the prognostic diagnosis and treatment of breast cancer.

Neuron-targeted liposomal coenzyme Q10 attenuates neuronal ferroptosis after subarachnoid hemorrhage by activating the ferroptosis suppressor protein 1/coenzyme Q10 system.

Subarachnoid hemorrhage (SAH) is primarily attributed to the rupture of intracranial aneurysms and is associated with a high incidence of disability and mortality. SAH disrupts the blood‒brain barrier, leading to the release of iron ions from blood within the subarachnoid space, subsequently inducing neuronal ferroptosis. A recently discovered protein, known as ferroptosis suppressor protein 1 (FSP1), exerts anti-ferroptotic effects by facilitating the conversion of oxidative coenzyme Q 10 (CoQ10) to its reduced form, which effectively scavenges reactive oxygen radicals and mitigates iron-induced ferroptosis. In our investigation, we observed an increase in FSP1 levels following SAH. However, the depletion of CoQ10 caused by SAH hindered the biological function of FSP1. Therefore, we created neuron-targeted liposomal CoQ10 by introducing the neuron-targeting peptide Tet1 onto the surface of liposomal CoQ10. Our objective was to determine whether this formulation could activate the FSP1 system and subsequently inhibit neuronal ferroptosis. Our findings revealed that neuron-targeted liposomal CoQ10 effectively localized to neurons at the lesion site after SAH. Furthermore, it facilitated the upregulation of FSP1, reduced the accumulation of malondialdehyde and reactive oxygen species, inhibited neuronal ferroptosis, and exerted neuroprotective effects both in vitro and in vivo. Our study provides evidence that supplementation with CoQ10 can effectively activate the FSP1 system. Additionally, we developed a neuron-targeted liposomal CoQ10 formulation that can be selectively delivered to neurons at the site of SAH. This innovative approach represents a promising therapeutic strategy for neuronal ferroptosis following SAH. STATEMENT OF SIGNIFICANCE: Subarachnoid hemorrhage (SAH) is primarily attributed to the rupture of intracranial aneurysms and is associated with a high incidence of disability and mortality. Ferroptosis suppressor protein 1 (FSP1), exerts anti-ferroptotic effects by facilitating the conversion of oxidative coenzyme Q 10 (CoQ10) to its reduced form, which effectively scavenges reactive oxygen radicals and mitigates iron-induced ferroptosis. In our investigation, we observed an increase in FSP1 levels following SAH. However, the depletion of CoQ10 caused by SAH hindered the biological function of FSP1. Therefore, we created neuron-targeted liposomal CoQ10. We find that it effectively localized to neurons at the lesion site after SAH and activated the FSP1/CoQ10 system. This innovative approach represents a promising therapeutic strategy for neuronal ferroptosis following SAH and other central nervous system diseases characterized by disruption of the blood-brain barrier.

A sensitive immunosensor via Pd@Au0.85Pd0.15 in situ electrocatalysis generating H2O2 for quenching electrochemiluminescence of Ir(pbi)2(acac)@Ti3C2Tx MXene-PVA.

The establishment of rapid target analysis methods for cytokeratin fragment antigen 21-1 (CYFRA 21-1) is urgently needed. [Ir(pbi)2(acac)] (pbi = 2-(4-bromophenyl)-1-hydrogen -benzimidazole, acac = acetylacetonate) as traditional electrochemiluminescence (ECL) luminophores has been confined due to its non-negligible dark toxicity and poor water solubility leading to poor biocompatibility and electrical conductivity as an organic molecule. Hence, to overcome this limitation, [Ir(pbi)2(acac)] can be effectively loaded on the polyvinyl alcohol hydrogel modified Ti3C2Tx MXene surface (Ir@Ti3C2Tx-PVA) as sensing platform which can emit high ECL signals. Then, a quenching strategy was proposed to fabricate an ECL sandwich immunosensor using H2O2 as quencher molecules which can generated by Pd@Au0.85Pd0.15. Especially, the generation of O2 to H2O2 can be achieved through a two-electron (2e-) reaction pathway by Pd@Au0.85Pd0.15, to overcome the restriction that the H2O2 was virtually impossible to label or immobilize on the non-enzyme nanomaterials. The proposed ECL assay achieves a response to CYFRA 21-1 within the range of 0.1 pg/mL-100 ng/mL, with a detection limit of 8.9 fg/mL (S/N = 3). This work provided a feasible tactic to seek superior-performance ECL luminophore and quencher consequently set up a novel means to makeup ultrasensitive ECL biosensor, which extended the utilization potential of Ir(pbi)2(acac) in ECL assays.

Quench-Type Electrochemiluminescence Immunosensor Based on Resonance Energy Transfer from Carbon Nanotubes and Au-Nanoparticles-Enhanced g-C3N4 to CuO@Polydopamine for Procalcitonin Detection.

A new type of sandwich electrochemiluminescence (ECL) immunosensor dependent on ECL resonance energy transfer (ECL-RET) to achieve sensitive detection of procalcitonin (PCT) has been designed. In brief, carbon nanotubes (CNT) and Au-nanoparticles-functionalized graphitic carbon nitride (g-C3N4-CNT@Au) and CuO nanospheres covered with polydopamine (PDA) layer (CuO@PDA) were synthesized and applied as ECL donor and receptor, respectively. g-C3N4-CNT nanomaterials were in situ prepared on the basis of π-π conjugation, and the CNT content in the composite were optimized to achieve a strong and stable ECL signal. At the same time, Au nanoparticles were used to functionalize g-C3N4-CNT to further increase the ECL intensity and the loading amount of primary antibody (Ab1). Moreover, CuO@PDA was first used to successfully quench the ECL signal of g-C3N4-CNT@Au. Under the optimum experimental conditions, the linear detection range for PCT concentration was within 0.0001-10 ng mL-1 and the detection limit was 25.7 fg mL-1 (S/N = 3). Considering prominent specificity, reproducibility, and stability, the prepared immunosensor was used to assess recovery rate of PCT in human serum according to the standard addition method and the result was satisfactory. In addition, it is worth mentioning that a novel ECL-RET pair of g-C3N4-CNT@Au (donor)/CuO@PDA (acceptor) was first developed, which offered an effective analytical tool for sensitive detection of biomarkers in early disease diagnostics.

Precise Drug Delivery by Using PLGA-Based Microspheres and Optical Manipulators.

The accurate delivery of precise amounts of drugs to a specific location can considerably affect various clinical applications. The precise control of drug amount and position is crucial to a successful drug delivery. This paper proposes the use of poly(lactide-co-glycolicacid) (PLGA)-based microspheres to contain precise amounts of drugs and an optical tweezer manipulator to transport these drug-containing microspheres to their targeted sites in vivo. The drugs were delivered by the PLGA-based microspheres to the yolk sac of zebrafish embryos, and a sustained drug release was observed to examine the anti-angiogenesis and angiogenesis activities. The PLGA-based microspheres degraded in zebrafish, thereby verifying that these microspheres can be used as drug carriers in vivo to ensure good biocompatibility and biodegradation. The proposed precise drug delivery approach can be used in protein tests and drug property characterization in vivo.

An atlas of nano-enabled neural interfaces.

Advances in microscopy and molecular strategies have allowed researchers to gain insight into the intricate organization of the mammalian brain and the roles that neurons play in processing information. Despite vast progress, therapeutic strategies for neurological disorders remain limited, owing to a lack of biomaterials for sensing and modulating neuronal signalling in vivo. Therefore, there is a pressing need for developing material-based tools that can form seamless biointerfaces and interrogate the brain with unprecedented resolution. In this Review, we discuss important considerations in material design and implementation, highlight recent breakthroughs in neural sensing and modulation, and propose future directions in neurotechnology research. Our goal is to create an atlas for nano-enabled neural interfaces and to demonstrate how emerging nanotechnologies can interrogate neural systems spanning multiple biological length scales.

Electrochemiluminescent competitive immunosensor based on polyethyleneimine capped SiO2 nanomaterials as labels to release Ru(bpy)32+ fixed in 3D Cu/Ni oxalate for the detection of aflatoxin B1.

In this work, a highly-efficient competitive method-based electrochemiluminescence (ECL) immunosensor was proposed based on {[Ru(bpy)3][Cu2xNi2(1-x)(ox)3]}n (Cu/Ni/Ru) as luminophor to efficiently detect aflatoxins B1 (AFB1). Cu/Ni/Ru exhibited excellent ECL behavior. While polyethyleneimine capped silicon dioxide (PEI@SiO2) could decrease the ECL performance of Cu/Ni/Ru due that PEI could destroy the structure of Cu/Ni/Ru via producing the complex between PEI and metal ions (Cu(II)/Ni(II)), inducing the release of Ru(bpy)32+. Since Au nanoparticles can directly combine with antibody and antigen, the Cu/Ni/Ru and PEI@SiO2 was functionalized by Au nanoparticles. The quantitative detection of AFB1 was based on the competitive binding between AFB1-bovine serum albumin labeled Au-PEI@SiO2 (Au-PEI@SiO2-AFB1-BSA) and free AFB1 with antibody-AFB1 which immobilized on Au-Cu/Ni/Ru. The ECL signal increased with augmenting the concentrations of the free AFB1 due to less Au-PEI@SiO2-AFB1-BSA combining with antibodies. Under optimal conditions, the proposed immunosensor exhibited a wide linear range from 0.01ngmL-1 to 100ngmL-1 with a detection limit of 0.0039ngmL-1 (S/N = 3). The proposed immunosensor also provides a promising approach for ultrasensitive detection of other mycotoxins.

Defining drug and target protein distributions after stent-based drug release: Durable versus deployable coatings.

BACKGROUND: Innovations in drug eluting stent designs make it increasingly important to develop models for differentiating performance through spatial definition of drug, receptor binding and cell state. METHODS: Two designs of sirolimus analog eluting stents were implanted into porcine coronary arteries for 28, 60 or 90 days (n = 9/time point), durable coating (Xience) and deployable absorbable coating (MiStent). Explanted arteries were evaluated for drug content (n = 3/time point) by LC-MS/MS and for drug and target protein (mTOR) distributions by immunofluorescence (IF, n = 6/time point). A computational model was developed to predict drug release and arterial distribution maps. RESULTS: Both stents released the majority of drug load by 28 days, with different tissue retention efficiencies (91.4 ±â€¯4.9% MiStent versus 21.5 ±â€¯1.9% Xience, P < 0.001). Computational modeling of MiStent coating deployment and microcrystal dissolution recapitulated in vivo drug release and net tissue content and predicted that >98.5% of deployed drug remains crystalline through 90 days. Immunofluorescence and computational modeling showed peristrut drug localization for both stents, with similar peaks, but high interstrut levels only at sites of coating deployment from the absorbable coating. Co-localization of mTOR-IF with drug-IF for both devices showed persistent drug effects, though with differential drug-receptor pharmacokinetics. CONCLUSIONS: Immunofluorescence and computational modeling provide insights into drug distribution and binding status that can help differentiate drug delivery technologies. Herein we found that tissue deployment of slow dissolving crystalline drug particles results in temporally and spatially more uniform drug delivery to interstrut zones that might otherwise be under-dosed without excess peristrut drug.

Sandwich-Type Electrochemiluminescence Sensor for Detection of NT-proBNP by Using High Efficiency Quench Strategy of Fe3O4@PDA toward Ru(bpy)32+ Coordinated with Silver Oxalate.

Heart failure (HF) is a burgeoning public health problem trigged by a heart circulation disorder. N-terminal pro-B-type natriuretic peptide (NT-proBNP) has been acknowledged as a prognostic biomarker for cardiac disease. Herein, a sandwich-type electrochemiluminescence (ECL) immunosensor was introduced for sensitive detection of NT-proBNP. Gold nanoparticle modified graphene oxide-Ru(bpy)32+/Ag2C2O4 was used as a luminophore and a desirable platform for immobilization of the captured antibodies. The more stable immobilization of plentiful Ru(bpy)32+ could be implemented by direct covalent bonding chelation with Ag2C2O4. More importantly, significant quenching can be achieved by introducing polydopamine (PDA) coated Fe3O4 onto the electrode via sandwich immunoreactions. The quenching mechanism mainly showed that the excited states of Ru(bpy)32+ could be annihilated by quinone units in PDA via energy transfer. The ECL quenching efficiency was logarithmically related to the concentration of the NT-proBNP in the range from 0.0005 ng/mL to 100.0 ng/mL with a detection limit of 0.28 pg/mL. Furthermore, this specific immunosensor presented good stability and repeatability as well as selectivity, which offers a guiding significance in both fundamental and clinical diagnosis of NT-proBNP.

Zinc-doping enhanced cadmium sulfide electrochemiluminescence behavior based on Au-Cu alloy nanocrystals quenching for insulin detection.

Novel and sensitive sandwich-type electrochemiluminescence (ECL) immunosensor was fabricated for insulin detection. Au-ZnCd14S combined nitrogen doping mesoporous carbons (Au-ZnCd14S/NH2-NMCs) acted as sensing platform and Au-Cu alloy nanocrystals were employed as labels to quench the ECL of Au-ZnCd14S/NH2-NMCs. Zinc-doping promoted the ECL behavior of CdS nanocrystals, with the best ECL emission obtained when the molar ratio of Zn/Cd was 1:14. Simultaneously, the modification of gold nanoparticles (Au NPs) and combination with NH2-NMC further enhanced the ECL emission of ZnCd14S due to its excellent conductivity and large specific surface area, which is desirable for the immunosensor construction. Au-Cu alloy nanocrystals were employed in the ECL system of ZnCd14S/K2S2O8 triggering ECL quenching effects. The ECL spectra of ZnCd14S, acting as the energy donor, exhibited well overlaps with the absorption band of Au-Cu alloy nanocrystals which acted as the energy acceptor, leading to an effective ECL resonance energy transfer (ECL-RET). On the basis of the ECL quenching effects, a sensitive ECL immunosensor for insulin detection was successfully constructed with a linear response range of insulin concentration from 0.1pg/mL to 30ng/mL and the limit of detection was calculated to be 0.03pg/mL (S/N = 3).

A sensitive electrochemiluminescence immunosensor based on Ru(bpy)32+ in 3D CuNi oxalate as luminophores and graphene oxide-polyethylenimine as released Ru(bpy)32+ initiator.

In this work, electrochemiluminescence (ECL) luminophor Ru(bpy)32+ was encapsulated in 3D CuNi oxalate and the synthesized metal-inorganic frameworks {[Ru(bpy)3][Cu2xNi2(1-x)(ox)3]}n (Ru/Cu/Ni) exhibited excellent and stable ECL signals, which could be decreased by polyethylenimine capped graphene oxide (GO-PEI). Based on this, a new sandwich ECL immunosensor was developed for detection of carcinoembryonic antigen (CEA). To capture primary antibody and second antibody more simply and efficiently, Ag nanoparticles were doped with Ru/Cu/Ni and GO-PEI. After a sandwich-type immunoreaction, a remarkable decrease of ECL signal was observed due to the release of Ru(bpy)32+ which was caused by the coordination between PEI and metal ions. Under the optimization of determination conditions, a linear response range for CEA from 0.1pgmL-1 to 100ngmL-1 was obtained, and the detection limit was calculated to be 0.027pgmL-1 (S/N=3). The prepared CEA immunosensor displayed high sensitivity, excellent stability and good specificity.

Light- and pH-activated intracellular drug release from polymeric mesoporous silica nanoparticles.

Surface modified mesoporous silica nanoparticles (MSNs) with reduced toxicity were prepared for light and pH dual triggerable drug delivery system. Both 413 nm light and acidic environment can activate the drug release process, improving the pharmacological action. By applying rhodamine B (RhB) as a model drug, the accumulative RhB release is as high as 95% in pH 5.0 and in irradiation of 413 nm light, compared to only 55% in pH 7.4 and in dark. The anti-cancer drug camptothecin (CPT) loaded nanoparticles can kill cancer cells with IC50 value of 0.02 µg mL(-1) in exposure of 413 nm light, which is much lower than free CPT (about 0.1 µg mL(-1)). Multimodal nonlinear optical imaging microscopy (NLOM) was employed to acquire in vitro coherent anti-Stokes Raman (CARS) and two-photon excited fluorescence (TPEF) images of live MCF-7 cells and showed that the nanoparticles can be taken up by breast tumor cell MCF-7 with high efficiency, indicating its great potential for anti-cancer drug delivery system.

Ocular biocompatibility evaluation of hydroxyl-functionalized graphene.

We have presented our recent efforts on genotoxicity and intraocular biocompatibility of hydroxylated graphene (G-OH) prepared by ball milling. We have previously demonstrated that the as-synthesized G-OH could be considered as an excellent alternative for graphene oxide which had been applied widely. Following our last report on G-OH, we carried out detailed studies on genotoxicity and in vivo biocompatibility of G-OH in this work. Less than 5% enhanced caspase-3 level was observed for cells exposed to more than 50 µg/mL G-OH over 72 h, suggesting G-OH caused cell apoptosis was slight. The G-OH induced DNA damage was also found to be mild since expression of p53 and ROS regeneration level was quite low even at high concentration of G-OH over a long time. Cell viability was found to be higher than 90% with 50 µg/mL G-OH and 80% with 100 µg/mL G-OH using flow cytometry. Comet results suggested that less than 5% tail could be found with 100 µg/mL G-OH. TEM results confirmed that G-OH could penetrate into and out of the cytoplasm by means of endocytosis and exocytosis without causing damage on cell membranes. In vivo biocompatibility of G-OH was studied by intravitreal injection of G-OH into rabbits. The ocular fundus photography results showed that G-OH could be diffused in the vitreous body gradually without any damage caused. Injection of G-OH had caused few damages on eyesight related functions such as intraocular pressure, electroretinogram and histological structures of the retina.

An electrochemiluminescence sensor for bromate assay based on a new cationic polythiophene derivative.

A sensitive electrochemiluminescence (ECL) sensor was fabricated for bromate assay based on a cationic polythiophene derivative, poly[3-(1,1'-dimethyl-4-piperidinemethylene)thiophene-2,5-diyl chloride] (PTh-D)/nafion modified Au electrode. Bromate was used as the coreactant as well as detecting analyte in the ECL sensor for the first time. The prepared PTh-D exhibited excellent solubility, strong and stable cathodic ECL activity. PTh-D can be immobilized on the surface of Au electrode via AuS bonding and nafion and chitosan were also used to immobilize PTh-D. The fabricated sensor exhibited a good linear relationship between the ECL intensities and the concentrations of BrO3(-) ranging from 1 µM to 0.1 M with a detection limit of 1 µM. This proposed method not only expands the application of PTh-D, but also opens new doors toward the detection of BrO3(-).

A novel multi-amplification photoelectrochemical immunoassay based on copper(II) enhanced polythiophene sensitized graphitic carbon nitride nanosheet.

A new sandwich photoelectrochemical (PEC) sensing strategy was proposed for the first time based on the increasing photocurrent of water-soluble polythiophene sensitized g-C3N4 nanosheet (PT-Cl/g-C3N4) in the presence of copper(II) (Cu(2+)), which was doped on the surface of titanium dioxide as labels for multi-amplification. Herein, the photoactive films of PT-Cl/g-C3N4 is employed as the photoactive antibody (Ab1) immobilization matrix for the subsequent sandwich-type antibody-antigen affinity interactions. Upon the presence of antigen (Ag), greatly enhanced photocurrent could be triggered in the PEC platform by the labels of second antibody (Ab2) of Cu(2+) doped titanium dioxide (Cu(2+)-TiO2). As a result of the multi-amplification in this Cu(2+)-TiO2 enhanced PT-Cl/g-C3N4-based PEC immunoassay, it possesses excellent analytical performance. The antigen could be detected from 0.01 pg mL(-1) to 100.0 ng mL(-1) with a detection limit of 5 fg mL(-1). This work opens up g-C3N4 nanosheet applied in PEC sensing. More importantly, the strategy of specific positive effect of Cu(2+) on the photocurrent of g-C3N4 opens an alternative horizon for PEC sensing.

Proteins used as sweeteners: a review.

For the prevention of obesity, diabetes, dental caries, and some metabolic disorders, ingestion of sugar should be restricted. Although they have high-potency sweetness, artificial low-calorie sweeteners can have severe adverse effects. Public demand for natural and healthy flavors, as well as perceived problems with the toxicity and taste quality of existing synthetic sweeteners, have led to efforts to find natural proteins with high sweetness and tast-modifying properties. Some important properties of natural protein sweeteners and taste-modifying protein sweeteners are discussed in this review.