A novel fluorescent and electrochemical dual-responsive immunosensor for sensitive and reliable detection of biomarkers based on cation-exchange reaction.

Sensitive and reliable detection of biomarkers is of vital importance in tumor early detection and clinical therapy. A novel fluorescent/electrochemical dual-responsive immunosensing platform for reliable and sensitive quantification of biomarkers was designed based on cation-exchange reaction. To construct such a versatile platform, the model analyte, carcinoembryonic antigen (CEA), was captured by magnetic Fe3O4 nanoparticles bound with primary antibodies (Fe3O4-Ab1) and then recognized by the detection antibodies conjugated complex containing poly(amidoamine) (PAMAM), carbon nanotube (CNT) and carboxyl functionalized CdSe nanocrystals (NCs) (CNT-PAMAM-CdSe NCs-Ab2). Via ligand exchange, the stable CdSe nanocrystals were easily functionalized with carboxylate ion (CdSe-COO-) and showed high hydrophilicity. The CdSe-COO- was effectively and densely conjugated to CNT coated dendrimer PAMAM that possesses large specific surface area. Finally, the target CEA was detected based on cation-exchange reaction (CER) by adding Ag+ to release thousands of cations Cd2+, which were detected by fluorescence and electrochemistry simultaneously. The electrochemical measurement was performed by directly detecting Cd2+ through square wave voltammetry (SWV), which displayed an excellent correlation with CEA from 5 pg/mL to 50 ng/mL, with a limit of detection (LOD) of 1.7 pg/mL. The fluorescence detection was implemented since free Cd2+ could trigger the weak fluorescence metal-sensitive dyes (Rhod-5N) to generate extremely high fluorescence signal. The fluorescence results showed the LOD for CEA detection was 0.25 pg/mL with a calibration curve range from 1 pg/mL to 20 ng/mL. The dual signal outputs showed an attractively self-correcting ability, which provides the capability of avoiding false positive signal and making the detection result more reliable. The proposed dual-responsive platform holds great promises for biomarkers detection in clinical diagnostics and therapy.

Amperometric sarcosine biosensor based on hollow magnetic Pt-Fe3O4@C nanospheres.

Sarcosine is a recently identified biomarker for prostate cancer. However, the rapid detection methods for sarcosine are relatively lack because of the low concentration and the presence of complicated interfering substances in serum or urine. In this manuscript, hollow nanospheres of Fe3O4 was synthesized and used as carrier to disperse Pt (Pt) nanoparticles. In order to achieve excellent electron transfer ability, we use polyaniline to coat Pt-Fe3O4 nanoparticles, and pyrolyze the polyaniline to carbon (C). Thus, hollow magnetic Pt-Fe3O4@C nanocomposites with good electron transfer ability are formed. The Pt-Fe3O4@C nanocomposites have high catalytic activity and stability. The nanocomposites were immobilized on glassy carbon electrode (GCE) to construct a nonenzyme hydrogen peroxide (H2O2) sensor (Pt-Fe3O4@C/GCE). We further construct a sensitive sarcosine biosensor by immobilizing sarcosine oxidase (SOx) on the Pt-Fe3O4@C/GCE. The high catalytic activity and good biocompatibility of Pt-Fe3O4@C nanocomposites greatly retained the bioactivity of immobilized SOx, and the prepared sarcosine biosensor has good electrocatalytic performance towards sarcosine. It has a linear detection range between 0.5 and 60 µM with a limit of detection (LOD) of 0.43 µM (the signal to noise ratio is 3), and the sensitivity is 3.45 nA µM-1 (48.8 nA µM-1 cm-2), which has the potential to be used for rapid screening of prostate cancer.

Amperometric sarcosine biosensor with strong anti-interference capabilities based on mesoporous organic-inorganic hybrid materials.

Amperometric enzyme biosensors are some of the simplest and cheapest types of medical devices used in the rapid detection of biomarkers that have been developed in the past fifty years. When the concentrations of biomarkers are at micromoles per liter, such as for sarcosine, which was recently discovered as a biomarker for prostate cancer, the response signal of the interferences is huge, and the biosensor is hard to satisfy the requirements of practical applications. In this manuscript, we describe a strategy for synthesizing a surface electronegative organic-inorganic hybrid mesoporous material, which could reduce the interference signal much better than Nafion and Chitosan. We verify that the surface potential of the carrier nanomaterial plays an important role in excluding anionic interferences. We also prepare a sensitive (16.35 µA mM-1), low LOD (0.13 µM) and wide linear range (1-70 µM) amperometric sarcosine biosensor with excellent anti-interference properties. This mesoporous material provides a bio-composite platform for the development of simple amperometric biosensors for detecting micromoles per liter of analytes in serum or urine.

CdTe@SiO2 signal reporters-based fluorescent immunosensor for quantitative detection of prostate specific antigen.

In this paper, an immunosensor using CdTe@SiO2 core-shell nanoparticles as labels was constructed for highly sensitive detection of prostate-specific antigen (PSA). In this approach, CdTe@SiO2 core-shell nanoparticles were synthesized using the sol-gel method. The additional Cd ions and sulfur source in SiO2 shell can greatly enhance the fluorescence intensity of CdTe nanocrystals. The reason is the formation of CdS-like cluster in SiO2 shell, which reduced the quantum size effect. The obtained CdTe@SiO2 nanoparticles also exhibited excellent biocompatibility, which was ideal for applying in biomarker detection. Furthermore, PSA capture antibodies functionalized magnetic Fe3O4 nanoparticles (Fe3O4-Ab1) were utilized in the proposed immunosensor to capture and enrich the PSA. The captured PSA was then immuno-recognized by CdTe@SiO2 labeled with PSA detection antibodies (CdTe@SiO2-Ab2) by forming the sandwich complex Fe3O4-Ab1/PSA/Ab2-CdTe@SiO2. The construction of this immunosensor was confirmed by fluorescence spectroscopy. The proposed immunosensor showed a good linear relationship between the fluorescent intensity and the target PSA concentration ranging from 0.01 to 5 ng/mL, and a detection limit as low as 0.003 ng/mL was achieved. The sensor also exhibited good specificity to PSA. This highly sensitive and specific immunosensor has great potential to be used in other biological detection.

Platinum-loaded mesoporous nickel phosphonate and its electrochemical application for sarcosine detection.

In 2009, Sreekumar found that sarcosine, as an effective biomarker, can be used to identify prostate cancer. However, it is difficult to detect sarcosine in urine or plasma because of its low concentration. In this work, we describe a simple strategy for the preparation of sarcosine biosensor based on platinum-loaded mesoporous nickel phosphonate (Pt/MNP) and subsequently apply it to detect sarcosine. Mesoporous structure could increase the active sites on the MNP surface, which makes the Pt/MNP have excellent electrochemical performance for detecting hydrogen peroxide, one of the enzymatic products, and the sarcosine biosensor exhibited a superior electrochemical performance. The linear range of sarcosine biosensor is from 5 to 40 µM and the sensitivity is 123.51 µA mM-1 cm-2. The limit of detection is estimated to be 0.24 µM (S/N = 3). Additionally, the sarcosine biosensor based on Pt/MNP also shows an excellent performance in the anti-interference test and the real serum sample. This work manifests the potential application of Pt/MNP as a novel biosensor material for sarcosine detection, which could be extended to other oxidase-based detection systems.

Exploring the Biocompatibility of Zwitterionic Copolymers for Controlling Macrophage Phagocytosis of Bacteria.

This paper provides a biomaterial derived from zwitterionic polymer for controlling macrophage phagocytosis of bacteria. A series of zwitterionic copolymers, named DMAPS-co-AA, are synthesized with 3-dimethyl (methacryloyloxyethyl) ammonium propane sulfonate (DMAPS) and acrylic acid (AA). The biocompatibility of DMAPS-co-AA copolymers can be adjusted by adjusting the DMAPS-content or pH value. As the DMAPS-content increases, the biocompatibility of zwitterionic copolymer increases. The zwitterionic copolymers with DMAPS content above 30 wt% have higher biocompatibility. Moreover, the biocompatibility also increases significantly as the pH increases from 3.4 to 7.2. By adjusting the pH above 5.8, the zwitterionic copolymer with lower DMAPS-content also shows higher biocompatibility. Importantly, after incubation with the DMAPS-co-AA copolymer solutions at different pH values, phagocytosis behavior of macrophage RAW264.7 cells can also be adjusted. The phagocytosis of bacteria is enhanced at pH = 7.2. Thus, it is proposed that zwitterionic copolymers can be used for controlling phagocytosis of bacteria.

Mesoporous Pt Nanotubes as a Novel Sensing Platform for Sensitive Detection of Intracellular Hydrogen Peroxide.

Controlling the shape, structure, and surface morphology of nanomaterials is of great significance in optimizing sensitivity and catalytic performances in biosensing applications. The main goal of employing Pt-based nanomaterials is to increase their utilization efficiency due to their high cost. Herein, we report the synthesis of mesoporous Pt nanotubes using Pluronic P123 as soft templates and Ag nanowires with 50 nm in diameter as hard templates. The resultant materials with unique structures show high sensitivity and stability toward H2O2 detection with low cellular cytotoxicity. The high sensitivity and catalytic properties are attributed to the mesopores and hollow structures making the inner Pt surfaces accessible to reaction media and enlarging the total surface area and one-dimensional structure facilitating the mass diffusion rate.

Nonsocial functions of hypothalamic oxytocin.

Oxytocin (OXT) is a hypothalamic neuropeptide composed of nine amino acids. The functions of OXT cover a variety of social and nonsocial activity/behaviors. Therapeutic effects of OXT on aberrant social behaviors are attracting more attention, such as social memory, attachment, sexual behavior, maternal behavior, aggression, pair bonding, and trust. The nonsocial behaviors/functions of brain OXT have also received renewed attention, which covers brain development, reproduction, sex, endocrine, immune regulation, learning and memory, pain perception, energy balance, and almost all the functions of peripheral organ systems. Coordinating with brain OXT, locally produced OXT also involves the central and peripheral actions of OXT. Disorders in OXT secretion and functions can cause a series of aberrant social behaviors, such as depression, autism, and schizophrenia as well as disturbance of nonsocial behaviors/functions, such as anorexia, obesity, lactation failure, osteoporosis, diabetes, and carcinogenesis. As more and more OXT functions are identified, it is essential to provide a general view of OXT functions in order to explore the therapeutic potentials of OXT. In this review, we will focus on roles of hypothalamic OXT on central and peripheral nonsocial functions.