Retracted Article: Berberine alleviates amyloid beta-induced injury in Alzheimer's disease by miR-107/ZNF217

Berberine plays a neuroprotective role in neurodegenerative disorders, including Alzheimer''s disease (AD). However, the underlying mechanism by which berberine inhibits AD progression remains largely unclear. The AD model was established using PC12 cells after treatment of amyloid beta (Aβ)_25-35. Cells were transfected with microRNA (miRNA)-107 mimic, inhibitor, zinc finger protein 217 (ZNF217) overexpression or corresponding negative controls. Cell viability, apoptosis and inflammatory cytokine secretion were measured by MTT, flow cytometry or enzyme linked immunosorbent assay, respectively. The expressions of miR-107, ZNF217 and phosphorylated tau (p-Tau) were detected by quantitative real-time polymerase chain reaction or Western blot. The association between miR-107 and ZNF217 was explored by luciferase reporter assay and RNA immunoprecipitation. Berberine attenuated Aβ_25-35-induced viability suppression in PC12 cells. Moreover, berberine inhibited the Aβ_25-35-induced increase of inflammatory cytokine expression, apoptosis and p-Tau level in PC12 cells. miR-107 expression was reduced in Aβ_25-35-treated PC12 cells and its overexpression alleviated Aβ_25-35-induced injury, which was further weakened by combination with berberine. ZNF217 was a target of miR-107 and its addition reversed miR-107-mediated inhibition of inflammatory injury, apoptosis and phosphorylation of tau. Besides, ZNF217 protein level was decreased by berberine via regulating miR-107 in Aβ_25-35-treated PC12 cells. Berberine protected against Aβ_25-35-induced inflammatory injury, apoptosis and phosphorylation of tau by regulating miR-107 and ZNF217, indicating berberine as a promising neuroprotective agent for therapeutics of AD.

Berberine plays a neuroprotective role in neurodegenerative disorders, including Alzheimer''s disease (AD).     

A gold nanoparticle based colorimetric and fluorescent dual-channel probe for acetylcholinesterase detection and inhibitor screening

Based on the competitive host–guest interaction between p-sulfonatocalix[6]arene (p-SC₆A) capped AuNPs and Rhodamine B (RhB)/acetylthiocholine, a fluorescent and colorimetric dual channel probe was developed for rapid detection of AChE with high sensitivity and selectivity. The detection limit was estimated to be 0.16 mU mL⁻¹. Crucially, due to the specific host–guest interaction, the high selectivity of the bioassay permitted the discrimination of AChE from other cations and proteins including biothiols and enzymes. Furthermore, the present method was also successfully applied to determinate AChE levels and screen AChE inhibitors in real cerebrospinal fluid (CSF) samples, which suggested that our proposed method has great potential to be applied in monitoring the disease progression and drug treatment effects of Alzheimer''s disease (AD).

A novel colorimetric and fluorescent dual-channel probe was developed for acetylcholinesterase detection and inhibitor screening with high sensitivity and selectivity.     

Modulation of aggregation with an electric field; scientific roadmap for a potential non-invasive therapy against tauopathies

Toxic aggregation of tau protein to neurofibrillary tangles (NFTS) is a central pathological event involved in tauopathies. Inhibition of tau protein aggregation can serve as a straightforward therapeutic strategy. However, tau-based therapeutic solutions are not very common. Phenothiazine methylene blue (tau protein inhibitor) is currently the only drug under phase III clinical trials. In this work, a non-invasive strategy is presented for modulating the aggregation of core peptide segments of tau protein (VQIVYK and VQIINK) by using electric fields of varying strengths. We use thioflavin T staining, tyrosine fluorescence assay, electron microscopy, IR, dynamic and static light scattering, and neuronal toxicity estimation, for verifying the effect of electric field on the aggregation kinetics, morphology, conformational state and cellular toxicity of peptide systems. Our observations suggest that electric field arrests the self-assembly of VQIVYK and VQIINK fibrils thereby reducing the neurotoxicity instigated by them. Based on our observations, we propose a prospective scheme for a futuristic non-invasive therapeutic device.

Potential use of electric field as a non-invasive therapeutic option against Alzheimer''s disease, by modulating the aggregation kinetics and morphology of tau protein.     

Possible neuroprotective effects of amide alkaloids from Bassia indica and Agathophora alopecuroides: in vitro and in silico investigations

In Alzheimer''s disease (AD), the accumulation of amyloid-β plaques, overactivity of MAO-B, and phosphorylated tau protein in the central nervous system result in neuroinflammation and cognitive impairments. Therefore, the multi-targeting of these therapeutic targets has emerged as a promising strategy for the development of AD treatments. The current study reports the isolation and identification of seven amide alkaloids, namely, N-trans-feruloyl-3-methoxytyramine (1), N-trans-feruloyltyramine (2), S-(−)-N-trans-feruloylnormetanephrine (3), S-(−)-N-trans-feruloyloctopamine (4), R-(+)-N-trans-feruloyloctopamine (5), N-trans-caffeoyltyramine (6), and S-(−)-3-(4-hydroxy-3-methoxyphenyl)-N-[2-(4-hydroxyphenyl)-methoxyethyl]acrylamide (7), from B. indica and A. alopecuroides, which are halophytic plants that have been reported to contain diverse phytochemicals. Additionally, the study explores the potential inhibition effects of the isolates on β-secretase, monoamine oxidase enzymes, and phosphorylated tau protein, and their anti-aggregation effects on amyloid-β fibrils. Compounds 1, 2, and 7 showed potent inhibitory activity against BACE1, MAO-B, and phosphorylated tau protein, as well as anti-aggregation activity against Aβ-peptides. Additionally, compound 6 displayed promising inhibition activity against MAO-B enzyme. Further in-depth in silico and modeling analyses (i.e., docking, absolute binding free energy calculations, and molecular dynamics simulations) were carried out to reveal the binding mode of each active compound inside the corresponding enzyme (i.e., MAO-B and BACE1). The results indicate that B. indica, A. alopecuroides, and the isolated amide alkaloids might be useful in the development of lead compounds for the prevention of neurodegenerative diseases, especially AD.

Bassia indica and Agathophora alopecuroides could be utilized as potential sources of candidate compounds for the management of Alzheimer disease.     

The recent development of donepezil structure-based hybrids as potential multifunctional anti-Alzheimer's agents: highlights from 2010 to 2020

Dementia is a term used to define different brain disorders that affect memory, thinking, behavior, and emotion. Alzheimer''s disease (AD) is the second cause of dementia that is generated by the death of cholinergic neurons (especially acetylcholine (ACh)), which have a vital role in cognition. Acetylcholinesterase inhibitors (AChEI) affect acetylcholine levels in the brain and are broadly used to treat Alzheimer''s. Donepezil, rivastigmine, and galantamine, which are FDA-approved drugs for AD, are cholinesterase inhibitors. In addition, scientists are attempting to develop hybrid molecules and multi-target-directed ligands (MTDLs) that can simultaneously modulate multiple biological targets. This review highlights recent examples of MTDLs and fragment-based strategy in the rational design of new potential AD medications from 2010 onwards.

This review highlights recent examples of multi-target-directed ligands (MTDLs) based on donepezil structure modification from 2010 onwards.     

A molecular journey to check the conformational dynamics of tau tubulin kinase 2 mutations associated with Alzheimer's disease

Proteins are one of the most vital components of biological functions. Proteins have evolutionarily conserved structures as the shape and folding pattern predominantly determine their function. Considerable research efforts have been made to study the protein folding mechanism. The misfolding of protein intermediates of large groups form polymers with unwanted aggregates that may initiate various diseases. Amongst the diseases caused by misfolding of proteins, Alzheimer''s disease (AD) is one of the most prevalent neuro-disorders which has a worldwide impact on human health. The disease is associated with several vital proteins and single amino acid mutations. Tau tubulin kinase 2 (TTBK2) is one of the kinases which is known to phosphorylate tau and tubulin. The literature strongly supports that the mutations-K50E, D163A, R181E, A184E and K143E are associated with multiple important cellular processes of TTBK2. In this study, to understand the molecular basis of the functional effects of the mutations, we have performed structural modeling for TTBK2 and its mutations, using computational prediction algorithms and Molecular Dynamics (MD) simulations. The MD simulations highlighted the impact of the mutations on the Wild Type (WT) by the conformational dynamics, Free Energy Landscape (FEL) and internal molecular motions, indicating the structural de-stabilization which may lead to the disruption of its biological functions. The destabilizing effect of TTBK2 upon mutations provided valuable information about individuals carrying this mutant which could be used as a diagnostic marker in AD.

MD simulations of TTBK2 mutants to study its impact on stability of the protein.     

Clinically oriented Alzheimer's biosensors: expanding the horizons towards point-of-care diagnostics and beyond

The development of minimally invasive and easy-to-use sensor devices is of current interest for ultrasensitive detection and signal recognition of Alzheimer''s disease (AD) biomarkers. Over the years, tremendous effort has been made on diagnostic platforms specifically targeting neurological markers for AD in order to replace the conventional, laborious, and invasive sampling-based approaches. However, the sophistication of analytical outcomes, marker inaccessibility, and material validity strongly limit the current strategies towards effectively predicting AD. Recently, with the promising progress in biosensor technology, the realization of a clinically applicable sensing platform has become a potential option to enable early diagnosis of AD and other neurodegenerative diseases. In this review, various types of biosensors, which include electrochemical, fluorescent, plasmonic, photoelectrochemical, and field-effect transistor (FET)-based sensor configurations, with better clinical applicability and analytical performance towards AD are highlighted. Moreover, the feasibility of these sensors to achieve point-of-care (POC) diagnosis is also discussed. Furthermore, by grafting nanoscale materials into biosensor architecture, the remarkable enhancement in durability, functionality, and analytical outcome of sensor devices is presented. Finally, future perspectives on further translational and commercialization pathways of clinically driven biosensor devices for AD are discussed and summarized.

Advancements of clinically driven biosensors in current Alzheimer''s diagnosis are highlighted in both in vitro and in vivo applications.     

Immunochromatographic assay for melamine based on luminescent quantum dot beads as signaling probes

To screen and detect the harmful substance melamine (MEL), a quantum-dot-bead-based immunochromatographic assay (QB-ICA) was formulated. After optimization, calibration was performed within the linear range from 0.06 to 0.28 ng mL⁻¹, with limit of detection (LOD) of 0.04 ng mL⁻¹. The LOD was 35 times lower than that of ICA that used colloidal gold nanoparticles (LOD = 1.4 ng mL⁻¹) and 40 times lower than that of the assay based on quantum dots (LOD = 1.6 ng mL⁻¹). In the detection of MEL in spiked pure milk using the proposed QB-ICA strategy, the LOD (LOD = 0.19 ng mL⁻¹) of the samples with the proposed pretreatment was 18.4 times lower than those of the samples without pretreatment (LOD = 3.5 ng mL⁻¹). The performance and practicability of the proposed QB-ICA system was validated; the obtained results reveal that QB-ICA is comparable with the conventional enzyme-linked immunosorbent assay (ELISA) method, but with enhanced applicability. Given its high sensitivity and practicability, the QB-ICA strategy could become a worthwhile alternative for the rapid, sensitive, and quantitative onsite detection of harmful substances, facilitating food safety monitoring.

An immunochromatographic assay using quantum dot beads as a label was established for melamine detection in milk with fast and effective pretreatment.     

Development of a HPLC-FL method to determine benzaldehyde after derivatization with N-acetylhydrazine acridone and its application for determination of semicarbazide-sensitive amine oxidase activity in human serum

A novel fluorescence labeling reagent N-acetylhydrazine acridone (AHAD) was designed and synthesized. A highly sensitive high performance liquid chromatography (HPLC) method coupled with fluorescence detection to determine benzaldehyde after derivatization with AHAD was developed. Optimum derivatization was obtained at 40 °C for 30 min with trichloroacetic acid as catalyst. Benzaldehyde derivative was separated on a reversed-phase SB-C18 column in conjunction with a gradient elution and detected by fluorescence detection at excitation and emission wavelengths of 371 nm and 421 nm. The established method exhibited excellent linearity over the injected amount of benzaldehyde of 0.003 to 5 nmol mL⁻¹. The method was successfully applied to the determination of serum semicarbazide-sensitive amine oxidase (SSAO) activity in humans. SSAO is a significant biomarker because serum SSAO activity is elevated in patients with Alzheimer''s disease, vascular disorders, heart disease and diabetes mellitus. It was demonstrated that the SSAO activity of the hyperglycemic group (60 ± 4 nmol mL⁻¹ h⁻¹) was significantly higher than that of normal blood sugar group (44 ± 4 nmol mL⁻¹ h⁻¹) with P < 0.05.

A highly sensitive HPLC-FL method to determine semicarbazide-sensitive amine oxidase activity was developed utilizing AHAD as the novel fluorescence labeling reagent.     

Smartphone-based surface plasmon resonance sensing platform for rapid detection of bacteria

Bacterial infection poses severe threats to public health, and early rapid detection of the pathogen is critical for controlling bacterial infectious diseases. Current methods are commonly labor intensive, time consuming or dependent on lab-based equipment. In this study, we proposed a novel and practical method for bacterial detection based on smartphones using the surface plasmon resonance (SPR) phenomena of gold nanoparticles (AuNPs). The proposed smartphone-based SPR sensing method is achieved by utilizing color development that arises from the change in interparticle distance of AuNPs induced by bacterial lysate. The pictures of bacteria/AuNPs color development were captured, and their color signals were acquired through a commercial smartphone. The proposed method has a detection range between 2.44 × 10⁵ and 1.25 × 10⁸ cfu mL⁻¹ and a detection limit of 8.81 × 10⁴ cfu mL⁻¹. Furthermore, this method has acceptable recoveries (between 85.7% and 95.4%) when measuring spiked real waters. Combining smartphone-based signal reading with AuNP-dependent color development also offers the following advantages: easy-to-use, real-time detection, free of complex equipment and low cost. In view of these features, this sensing platform would have widespread applications in the fields of medical, food, and environmental sciences.

In this study, we propose a novel and practical method for bacterial detection based on smartphones using the surface plasmon resonance (SPR) phenomena of gold nanoparticles (AuNPs).     

Synthetic and biochemical studies on the effect of persulfidation on disulfide dimer models of amyloid β42 at position 35 in Alzheimer's etiology

Protein persulfidation plays a role in redox signaling as an anti-oxidant. Dimers of amyloid β42 (Aβ42), which induces oxidative stress-associated neurotoxicity as a causative agent of Alzheimer''s disease (AD), are minimum units of oligomers in AD pathology. Met35 can be susceptible to persulfidation through its substitution to homoCys residue under the condition of oxidative stress. In order to verify whether persulfidation has an effect in AD, herein we report a chemical approach by synthesizing disulfide dimers of Aβ42 and their evaluation of biochemical properties. A homoCys-disulfide dimer model at position 35 of Aβ42 formed a partial β-sheet structure, but its neurotoxicity was much weaker than that of the corresponding monomer. In contrast, the congener with an alkyl linker generated β-sheet-rich 8–16-mer oligomers with potent neurotoxicity. The length of protofibrils generated from the homoCys-disulfide dimer model was shorter than that of its congener with an alkyl linker. Therefore, the current data do not support the involvement of Aβ42 persulfidation in Alzheimer''s disease.

Our data do not support the Aβ42 persulfidation hypothesis in Alzheimer''s etiology because the neurotoxicity of the homoCys-disulfide-Aβ42 dimer was very weak.     

Inhibition of metal-induced amyloid β-peptide aggregation by a blood–brain barrier permeable silica–cyclen nanochelator

Alzheimer''s disease (AD) is a neurodegenerative malady associated with amyloid β-peptide (Aβ) aggregation in the brain. Metal ions play important roles in Aβ aggregation and neurotoxicity. Metal chelators are potential therapeutic agents for AD because they could sequester metal ions from the Aβ aggregates and reverse the aggregation. The blood–brain barrier (BBB) is a major obstacle for drug delivery to AD patients. Herein, a nanoscale silica–cyclen composite combining cyclen as the metal chelator and silica nanoparticles as a carrier was reported. Silica–cyclen was characterized by scanning electron microscopy (SEM), transmission electron microscopy (TEM), Fourier transform infrared (FT-IR) and dynamic light scattering (DLS). The inhibitory effect of the silica–cyclen nanochelator on Zn²⁺- or Cu²⁺-induced Aβ aggregation was investigated by using a BCA protein assay and TEM. Similar to cyclen, silica–cyclen can effectively inhibit the Aβ aggregation and reduce the generation of reactive oxygen species induced by the Cu–Aβ₄₀ complex, thereby lessening the metal-induced Aβ toxicity against PC12 cells. In vivo studies indicate that the silica–cyclen nanochelator can cross the BBB, which may provide inspiration for the construction of novel Aβ inhibitors.

A BBB-passable nanoscale silica–cyclen chelator effectively reduces the metal-induced Aβ aggregates and related ROS, thereby decreasing the neurotoxicity of Aβ.     

Monascus pigment rubropunctatin derivative FZU-H reduces Aβ(1-42)-induced neurotoxicity in Neuro-2A cells

Alzheimer''s disease (AD) is an extremely complex disease, characterized by several pathological features including oxidative stress and amyloid-β (Aβ) aggregation. Blockage of Aβ-induced injury has emerged as a potential therapeutic approach for AD. Our previous efforts resulted in the discovery of Monascus pigment rubropunctatin derivative FZU-H with potential neuroprotective effects. This novel lead compound significantly diminishes toxicity induced by Aβ(1-42) in Neuro-2A cells. Our further mechanism investigation revealed that FZU-H inhibited Aβ(1-42)-induced caspase-3 protein activation and the loss of mitochondrial membrane potential. In addition, treatment of FZU-H was proven to attenuate Aβ(1-42)-induced cell redox imbalance and Tau hyperphosphorylation which caused by okadaic acid in Neuro-2A cells. These results indicated that FZU-H shows promising neuroprotective effects for AD.

Monascus pigment rubropunctatin derivative FZU-H shows promising neuroprotective effects for AD.     

Simple and rapid monitoring of doxorubicin using streptavidin-modified microparticle-based time-resolved fluorescence immunoassay

Developing a simple analytical method suitable for therapeutic drug monitoring in a clinical setting is key to establishing guidelines on accurate dose administration and the advancement of precision medicine. We devised a simple rapid analytical method through the combination of streptavidin-modified microparticles and a time-resolved fluorescence immunoassay for therapeutic drug monitoring. The analytical performance of this method was investigated and validated using clinical samples. By determination of doxorubicin concentration, the proposed assay has shown a satisfactory linear range of detection (3.8–3000 ng mL⁻¹) with a limit of detection of 3.8 ng mL⁻¹ and an IC₅₀ of 903.9 ng mL⁻¹. The intra and inter-assay coefficients of variation were 4.12–5.72% and 5.48–6.91%, respectively, and the recovery was acceptable. The applicability of the proposed assay was assessed by comparing the determined results with those measured by LC-MS/MS, presenting a satisfactory correlation (R² = 0.9868). The proposed assay, which shows satisfactory analytical performance, has great potential for application in the field of TDM in the future.

Simple, rapid SA-MPs based TRFIA, is applied in therapeutic drug monitoring and the analytical performance is comparable with LC-MS/MS.     

A new G-triplex-based strategy for sensitivity enhancement of the detection of endonuclease activity and inhibition

EcoRI is an important biomacromolecule in live cells and protects bacterial cells against foreign DNA. In this work, we developed a simple and convenient G-triplex (G3) (5′-TGGGAAGGGAGGGAATTCCCT-3′)-based colorimetric assay for the rapid and selective detection of EcoRI activity and inhibition. The sequence specifically responds to EcoRI in the presence of K⁺ and hemin to form a G-triplex/hemin complex. Taking advantage of G-triplex, EcoRI activity was investigated under the optimized conditions. The absorption intensity ratio displayed a linear relationship against the concentration of EcoRI in the range 0 to 100 U mL⁻¹, and the detection limit was 5.7 U mL⁻¹. Furthermore, G3 showed good selectivity, and the ability to be used to screen for EcoRI inhibitors, indicating its potential in detection and analysis applications.

A new G-triplex-based probe was developed for detecting EcoRI activity and inhibition. The probe showed good selectivity towards EcoRI. The assay was colorimetric and can be monitored by the naked eye.     

Development of novel N-(6-methanesulfonyl-benzothiazol-2-yl)-3-(4-substituted-piperazin-1-yl)-propionamides with cholinesterase inhibition,anti-β-amyloid aggregation,neuroprotection and cognition enhancing properties for the therapy of Alzheimer's disease

A novel series of benzothiazole–piperazine hybrids were rationally designed, synthesized, and evaluated as multifunctional ligands against Alzheimer''s disease (AD). The synthesized hybrid molecules illustrated modest to strong inhibition of acetylcholinesterase (AChE) and Aβ_1-42 aggregation. Compound 12 emerged as the most potent hybrid molecule exhibiting balanced functions with effective, uncompetitive and selective inhibition against AChE (IC₅₀ = 2.31 μM), good copper chelation, Aβ_1-42 aggregation inhibition (53.30%) and disaggregation activities. Confocal laser scanning microscopy and TEM analysis also validate the Aβ fibril inhibition ability of this compound. Furthermore, this compound has also shown low toxicity and is capable of impeding loss of cell viability elicited by H₂O₂ neurotoxicity in SHSY-5Y cells. Notably, compound 12 significantly improved cognition and spatial memory against scopolamine-induced memory deficit in a mouse model. Hence, our results corroborate the multifunctional nature of novel hybrid molecule 12 against AD and it may be a suitable lead for further development as an effective therapeutic agent for therapy in the future.

A novel series of benzothiazole–piperazine hybrids were rationally designed, synthesized, and evaluated as multifunctional ligands against Alzheimer''s disease (AD).     

Photo-induced synthesis,structure and in vitro bioactivity of a natural cyclic peptide Yunnanin A analog

A cyclic analog of natural peptide Yunnanin A was synthesized via photoinduced single electron transfer reaction (SET) in the paper. The resulting compound exhibited potent bioactivity (with IC₅₀ values 29.25 μg mL⁻¹ against HepG-2 cell lines and 65.01 μg mL⁻¹ against HeLa cell lines), but almost have no toxicity to normal cells (with IC₅₀ values 203.25 μg mL⁻¹ against L929 cell lines), which may be served as a potential antitumor drug for medical treatment. The spatial structure was examined by experimental electronic circular dichroism (ECD) and quantum chemistry calculations. Moreover, the theoretical study suggested that special intramolecular hydrogen bonds and γ, β-turn secondary structures may be possible sources affecting cyclic peptide''s bioactivity.

The photo-induced synthesis, structure and in vitro bioactivity study of a Yunnanin A cyclopeptide analog was presented.     

The anti-Alzheimer potential of Tamarindus indica: an in vivo investigation supported by in vitro and in silico approaches

Tamarindus indica Linn. (Tamarind, F. Fabaceae) is one of the most widely consumed fruits in the world. A crude extract and different fractions of T. indica (using n-hexane, dichloromethane, ethyl acetate, and n-butanol) were evaluated in vitro with respect to their DPPH scavenging and AchE inhibition activities. The results showed that the dichloromethane and ethyl acetate fractions showed the highest antioxidant activities, with 84.78 and 86.96% DPPH scavenging at 0.10 μg mL⁻¹. The n-hexane, dichloromethane, and ethyl acetate fractions inhibited AchE activity in a dose-dependent manner, and the n-hexane fraction showed the highest inhibition at 20 μg mL⁻¹. The results were confirmed by using n-hexane, dichloromethane, and ethyl acetate fractions in vivo to regress the neurodegenerative features of Alzheimer''s dementia in an aluminum-intoxicated rat model. Phytochemical investigations of those three fractions afforded two new diphenyl ether derivative compounds 1–2, along with five known ones (3–7). The structures of the isolated compounds were confirmed via 1D and 2D NMR and HRESIMS analyses. The isolated compounds were subjected to extensive in silico-based investigations to putatively highlight the most probable compounds responsible for the anti-Alzheimer activity of T. indica. Inverse docking studies followed by molecular dynamics simulation (MDS) and binding free energy (ΔG) investigations suggested that both compounds 1 and 2 could be promising AchE inhibitors. The results presented in this study may provide potential dietary supplements for the management of Alzheimer''s disease.

In vivo anti-Alzheimer''s and antioxidant potential of Tamarindus indica supported by molecular docking.     

AuNP array coated substrate for sensitive and homogeneous SERS-immunoassay detection of human immunoglobulin G

Owing to the high sensitivity, fast responsiveness and high specificity, immunoassays using surface-enhanced Raman scattering (SERS) as the readout signal displayed great potential in disease diagnosis. In this study, we developed a SERS-immunoassay method for the detection of human immunoglobulin G (HIgG). Upon involving well-ordered AuA on a SERSIA substrate, the LSPR effect was further enhanced to generate a strong and uniform Raman signal through the formation of sandwich structure with the addition of target HIgG and SERSIA tag. Optimization of the assay provided a wide linear range (0.1–200 μg mL⁻¹) and low limit of detection (0.1 μg mL⁻¹). In addition, the SERS-immunoassay method displayed excellent specificity and was homogeneous, which guaranteed the practical use of this method in the quantitative detection of HIgG. To validate this assay, human serum was analysed, which demonstrated the potential advantages of SERS-immunoassay technology in clinical diagnostics.

An AuNP array coated substrate was developed for the SERS-immunoassay detection of human immunoglobulin G.     

A ratiometric fluorescence sensor based on enzymatically activatable micellization of TPE derivatives for quantitative detection of alkaline phosphatase activity in serum

A novel ratiometric fluorescence assay via enzymatically activatable micellization in aqueous solution was devised for quantitative detection of alkaline phosphatase (ALP) activity. We demonstrated that the dephosphorylation of the water-soluble, phosphate-functionalized, fluorophore monomer P-TPE-TG, induced by an enzymatic reaction of ALP, leads to micelle formation in aqueous solution because its water-soluble functionality is reduced. The dephosphorylation-induced micellization of P-TPE-TG exhibited a ratiometric sensing response for various ALP concentrations (10–200 mU mL⁻¹) and provided a suitable sensing platform for naked eye detection with increased fluorescence quantum yield (Φ = 3.2%), even compared to a typical TPE-based sensor (Φ = 1.0%), where ALP can be sensed with a detection limit of 0.034 mU mL⁻¹. In addition, P-TPE-TG displayed excellent sensing performance at concentrations from 0 to 50 mU mL⁻¹ in diluted human serum (10%), which offers the capability to exploit ratiometric responses for bioactive substances under practical conditions.

A novel ratiometric fluorescence assay via enzymatically activatable micellization in aqueous solution was devised for quantitative detection of alkaline phosphatase (ALP) activity.