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1.
Bioelectrochemistry ; 159: 108729, 2024 May 15.
Artículo en Inglés | MEDLINE | ID: mdl-38772096

RESUMEN

This study explores the principles of resonance energy transfer and adsorption modulation using composites of Cu2S-MPA/NGODs. These composites can efficiently control the quenching process of electrochemiluminescence (ECL). Mercaptopropionic acid (MPA) was added during the synthesis of Cu2S-MPA to enhance its attachment to nitrogen-doped graphene quantum dots (NGODs). The UV absorption peaks of NGODs coincided with the emission peaks of luminol ECL, enabling resonance energy transfer and enhancing the quenching capability of Cu2S-MPA. Meanwhile, there is another quenching strategy. When the readily reducible Cu+ ions underwent partial reduction to Cu when they were bound to NGODs. This weakened the electrocatalytic effect on reactive oxygen species (ROS) and had a detrimental impact on electron transfer. Under optimal conditions, the immunosensor ECL intensity decreased linearly with the logarithm of carcinoembryonic antigen (CEA) concentration in the range of 0.00001-40 ng/mL, with a detection limit of 0.269 fg/mL. The sensor was effectively utilized for the identification of CEA in actual serum samples.

2.
Immunol Res ; 2024 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-38691319

RESUMEN

Recent advances in cancer immunotherapy, especially immune checkpoint inhibitors (ICIs), have revolutionized the clinical outcome of many cancer patients. Despite the fact that impressive progress has been made in recent decades, the response rate remains unsatisfactory, and many patients do not benefit from ICIs. Herein, we summarized advanced studies and the latest insights on immune inhibitory factors in the tumor microenvironment. Our in-depth discussion and updated landscape of tumor immunosuppressive microenvironment may provide new strategies for reversing tumor immune evasion, enhancing the efficacy of ICIs therapy, and ultimately achieving a better clinical outcome.

3.
Front Pharmacol ; 15: 1243353, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38482051

RESUMEN

Introduction: Gypenoside is a natural extract of Gynostemma pentaphyllum (Thunb.) Makino, a plant in the Cucurbitaceae family. It has been reported to have antitumor effects on the proliferation, migration and apoptosis of various types of cancer cells. However, the use of gypenoside in the treatment of gastric cancer has not been studied. In the present study, we explored the therapeutic effect of gypenoside on gastric cancer and the potential molecular mechanism. Methods and Results: Our results showed that gypenoside induced apoptosis in HGC-27 and SGC-7901 cells in a time-dependent and dose-dependent manner. Network pharmacology analyses predicted that gypenoside exerts its therapeutic effects through the PI3K/AKT/mTOR signaling pathway. Furthermore, molecular docking and western blot experiments confirmed that gypenoside induced the apoptosis of gastric cancer cells through the PI3K/AKT/mTOR signaling pathway. In addition, network pharmacological analysis revealed that the common targets of gypenoside in gastric cancer were enriched in the immune effector process, PD-L1 expression, the PD-1 checkpoint pathway, and the Jak-STAT signaling pathway. Furthermore, molecular docking and western blot assays demonstrated that gypenoside could bind to STAT3 and reduce its phosphorylation. Thus, the transcription of PD-L1 was inhibited in gastric cancer cells. Moreover, coculture experiments of gastric cancer cells with gypenoside and primary mouse CD8+ T cells showed that gastric cancer cells treated with gypenoside could enhance the antitumor ability of T cells. Animal experiments confirmed the antitumor effect of gypenoside, and the expression of PD-L1 was significantly downregulated in the gypenoside-treated group. Conclusion: Gypenoside induced the apoptosis of gastric cancer cells by inhibiting the PI3K/AKT/mTOR pathway and simultaneously inhibited the expression of PD-L1 in gastric cancer cells, thus enhancing the antitumor immunity of T cells. This study provides a theoretical basis for applying gypenoside as a new therapeutic agent to enhance the efficacy of immunotherapy in gastric cancer.

4.
Biosens Bioelectron ; 252: 116151, 2024 May 15.
Artículo en Inglés | MEDLINE | ID: mdl-38402725

RESUMEN

Perylene diimide (PDI) is a readily reducible electron-deficient dye that exhibits strong photoluminescent properties, providing new opportunities for synthesizing novel electrochemiluminescence (ECL) emitters. In this study, ethylene glycol (EG) was used to induce the self-assembly of PDI supramolecules for the preparation of ultrathin EG-PDI nanosheets characterized by low crystallinity and weak stacking interaction. Notably, EG-PDI integrates luminescent and catalytic functions into one device, accelerating the interfacial electron transfer and the faster charge transfer kinetics of EG-PDI with K2S2O8. Furthermore, the narrow band gap of EG-PDI facilitates its excitation at an ultra-low potential (-0.3 V). To improve the efficiency of tumor marker analysis, multifunctional Au nanostars (ANS) was introduced both as an energy acceptor of the ECL system and a probe for the photothermal system. Dual-mode immunoassay have demonstrated superior analytical performance in detecting alpha-fetoprotein (AFP), meeting the requirements of modern clinical diagnostics in resource-limited environments.


Asunto(s)
Técnicas Biosensibles , Imidas , Perileno/análogos & derivados , Inmunoensayo , Glicoles de Etileno
5.
Neoplasia ; 48: 100966, 2024 02.
Artículo en Inglés | MEDLINE | ID: mdl-38237304

RESUMEN

Although immune checkpoint therapy has significantly improved the prognosis of patients with melanoma, urgent attention still needs to be paid to the low patient response rates and the challenges of precisely identifying patients before treatment. Therefore, it is crucial to investigate novel immunosuppressive mechanisms and targets in the tumor microenvironment in order to reverse tumor immune escape. In this study, we found that the cell cycle checkpoint Aurora kinase B (AURKB) suppressed the anti-tumor immune response, and its inhibitor, Tozasertib, effectively activated T lymphocyte cytokine release in vitro and anti-tumor immunity in vivo. Tozasertib significantly inhibited melanoma xenograft tumor growth by decreasing the number of inhibitory CD4+ Treg cells in the tumors, which, in turn, activated CD8+ T cells. Single-cell analysis revealed that AURKB suppressed anti-tumor immunity by increasing MIF-CD74/CXCR4 signaling between tumor cells and lymphocytes. Our study suggests that AURKB is a newly identified anti-tumor immunity suppressor, whose inhibitors may be developed as novel anti-tumor immunity drugs and may have synergistic anti-melanoma effects with immune checkpoint therapies.


Asunto(s)
Antineoplásicos , Melanoma , Humanos , Melanoma/patología , Linfocitos T Reguladores , Linfocitos T CD8-positivos , Antineoplásicos/uso terapéutico , Microambiente Tumoral
6.
J Transl Med ; 22(1): 96, 2024 Jan 23.
Artículo en Inglés | MEDLINE | ID: mdl-38263194

RESUMEN

BACKGROUND: Periodontitis is a chronic oral inflammatory disease that seriously affects people's quality of life. The purpose of our study was to investigate the correlation between the systemic immune inflammation index (SII) and periodontitis by utilizing a large national survey. This will establish a reference for the early identification and management of periodontitis. METHODS: This study comprised the adult US population who participated in a national periodontitis surveillance project during the six years from 2009 to 2014. Through the utilization of univariate and multivariate weighted logistic regression, we investigated the correlation between the systemic immune inflammation index and periodontitis. Additionally, we employed sensitivity analyses to evaluate the robustness of our findings. RESULTS: The study involved 10,366 participants with an average age of 51.00 years, of whom 49.45% were male (N = 5126) and 50.55% were female (N = 5240). The prevalence of periodontitis is estimated to be about 38.43% in the US adults aged 30 or older population. Our logistic regression models indicated a positive association between a SII higher than 978 × 109/L and periodontitis. The elder group (aged 50 or older) with SII higher than 978 × 109/L demonstrated a significant correlation with periodontitis in the fully adjusted model (Odds Ratio [OR] = 1.409, 95% Confidence Interval [CI] 1.037, 1.915, P = 0.022). However, there is no statistical difference among adults aged 30 to 50. The robustness of our findings was confirmed through sensitivity analyses. CONCLUSIONS: Our study highlights that SII is associated with periodontitis in a nationally representative sample of US adults. And the SII is significantly associated with a high risk of periodontitis in individuals aged 50 or older.


Asunto(s)
Periodontitis , Calidad de Vida , Adulto , Femenino , Masculino , Humanos , Persona de Mediana Edad , Estudios Transversales , Inflamación , Modelos Logísticos
7.
Small ; : e2310476, 2024 Jan 28.
Artículo en Inglés | MEDLINE | ID: mdl-38282388

RESUMEN

In recent years, carbon nitride (CN) has attracted substantial attention in the field of electrochemiluminescence (ECL) applications, owing to its outstanding optical and electronic properties. However, the passivation of CN during the ECL process has contributed to reduced stability and poor repeatability. While some studies have tried to boost ECL performance by altering CN through doping and vacancies, effectively suppressing CN passivation at high potentials continues to be challenge. In this study, the built-in electric field and the Schottky barrier effect is used to expedite the transfer of electrons from CN to the molybdenum disulfide (MoS2 ) conduction band. This transfer deterred excessive electron injection into the CN band, thus mitigating its electrochemical degradation. Moreover, by introducing nickel nanoparticles (Ni NPs) as catalytic active sites, it is facilitated that the decomposition of potassium persulfate (K2 S2 O8 ), thereby enhancing both the stability and intensity of ECL emission. In the end, the application of ternary heterostructure as sensing platform for the cancer biomarker carcinoembryonic antigen (CEA) demonstrated high sensitivity. This research introduces a novel approach to overcome CN passivation, paving the way for more promising applications of CN in energy, environmental, and biosensing fields.

8.
Bioelectrochemistry ; 156: 108626, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38128442

RESUMEN

By combining two different materials, metal-organic frameworks (MOF) and ß-cyclodextrins (ß-CD), a signal amplification electrochemical luminescence (ECL) immunosensor was constructed to realize the sensitive detection of AFP. The indium-based metal-organic framework (In-MOF) was used as the carrier of Ru(bpy)32+, and Ru(bpy)32+ was immobilized by In-MOF through suitable pore size and electrostatic interaction. At the same time, using host-guest recognition, ß-CD enriched TPA into the hydrophobic cavity for accelerating the electronic excitation of TPA, then, achieving the purpose of signal amplification. The signal amplification immunosensor structure is constructed among the primary antibody Ab1 connected to the Ru(bpy)32+@In-MOF modified electrode, AFP, BSA and the secondary antibody (Ab2) loaded with TPA-ß-CD. The immunosensor has a good linearity in the range of 10-5 ng/mL-50 ng/mL, and the low limit of detection (LOD) is 1.1 × 10-6 ng/mL. In addition, the electrochemiluminescence immunosensor that we designed has strong stability, good selectivity and repeatability, which provides a choice for the analysis of AFP.


Asunto(s)
Técnicas Biosensibles , Nanopartículas del Metal , Estructuras Metalorgánicas , beta-Ciclodextrinas , Nanopartículas del Metal/química , alfa-Fetoproteínas , Mediciones Luminiscentes , Inmunoensayo , Límite de Detección , Estructuras Metalorgánicas/química , Técnicas Electroquímicas
9.
Anal Chem ; 95(44): 16225-16233, 2023 11 07.
Artículo en Inglés | MEDLINE | ID: mdl-37877873

RESUMEN

Compared with the accuracy of a single signal and the limitation of environmental applicability, the application value of dual-mode detection is gradually increasing. To this end, based on the photothermal effect of Ag/Co embedded N-rich mesoporous carbon nanomaterials (AgCo@NC NPs), we designed a dual-mode signal response system for the detection of α-fetoprotein (AFP). First, AgCo@NC NPs act as a photothermal immunoprobe that converts light energy into heat driven by a near-infrared (NIR) laser and obtains temperature changes corresponding to the analyte concentration on a hand-held thermal imager. In addition, this temperature recognition system can significantly improve the efficiency of Fenton-like reactions. AgCo@NC NPs act as peroxidase mimics to initiate the generation of poly N-isopropylacrylamide (PNIPAM, resistance enhancer) by cascade catalysis and the degradation of methylene blue (MB), thus enabling electrochemical testing. The dual-mode assay ranges from 0.01 to 100 and 0.001-10 ng/mL, with lower limits of detection (LOD) of 3.2 and 0.089 pg/mL, respectively, and combines visualization, portability, and high efficiency, opening new avenues for future clinical diagnostics and inhibitor studies.


Asunto(s)
Nanoestructuras , alfa-Fetoproteínas , Luz
10.
Anal Chem ; 95(33): 12459-12469, 2023 Aug 22.
Artículo en Inglés | MEDLINE | ID: mdl-37566460

RESUMEN

To sensitively monitor trace amounts of alternariol (AOH) in fruits, a dual-mode aptamer sensor utilizing the dual-function nanomaterial PoPD/Ru-Au was developed. This sensor provides both electrochemical (EC) and electrochemiluminescence (ECL) signals, which can greatly avoid the potential false positive of the traditional single signal, thus enhancing the accuracy and reliability of detection results. Polyo-phenylenediamine (PoPD), known for its favorable EC response, can also assist in enhancing the ECL behavior of Ru-Au. Furthermore, Ru-Au demonstrates excellent ECL performance and effectively activates K2S2O8 to amplify the EC response of PoPD. The complementary effect of the two can effectively amplify the final detection signal. Additionally, the PoPD/Ru-Au nanomaterial exhibits excellent electrical conductivity, further enhancing the EC and ECL response signals. The experimental results demonstrate that the EC detection range of AOH was 0.01-100 ng/mL, while the ECL detection range was 0.001-100 ng/mL, both exhibiting a satisfactory linear relationship. Therefore, the mutual verification of the detection results can be highly realized, and the purpose of avoiding wrong detection can be achieved.

11.
FEBS J ; 290(24): 5720-5743, 2023 12.
Artículo en Inglés | MEDLINE | ID: mdl-37581853

RESUMEN

Src homolog and collagen homolog binding protein 1 (SHCBP1) binds to the SH2 domain of SHC-transforming protein 1 (SHC1) and is involved in midbody organization and cytokinesis completion. SHCBP1 has been reported to be a cancer driver gene, promoting cancer progression. However, the functional role and underlying mechanism of SHCBP1 in regulating lung adenocarcinoma (LUAD) cell proliferation and migration are incompletely understood. Here, we discovered that SHCBP1 is overexpressed in LUAD tissues and is associated with a poor prognosis. SHCBP1 knockdown inhibited LUAD cell proliferation and migration by arresting the cell cycle and preventing epithelial-mesenchymal transition (EMT) via decreasing cyclin-dependent kinase 1 (CDK1) expression. Mechanistically, CDK1 overexpression reversed SHCBP1 knockdown-induced inhibition of proliferation and migration, confirming CDK1 as a key downstream target of SHCBP1. In addition, we proposed that rucaparib may be a small-molecule inhibitor of SHCBP1 and validated both in vitro and in vivo that rucaparib inhibits cell proliferation and migration via suppression of the SHCBP1/CDK1 pathway in LUAD. Our study elucidates a newly identified role of SHCBP1 in promoting cell proliferation and migration in LUAD, and suggests rucaparib as a potential inhibitor for LUAD treatment.


Asunto(s)
Adenocarcinoma del Pulmón , Neoplasias Pulmonares , Humanos , Proteína Quinasa CDC2/genética , Adenocarcinoma del Pulmón/tratamiento farmacológico , Adenocarcinoma del Pulmón/genética , Proliferación Celular , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/genética , Movimiento Celular , Línea Celular Tumoral , Regulación Neoplásica de la Expresión Génica , Proteínas Adaptadoras de la Señalización Shc
12.
EBioMedicine ; 94: 104724, 2023 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-37480625

RESUMEN

BACKGROUND: Cancer is the world's leading cause of death and a key hindrance to extending life expectancy. Celastrol, a bioactive compound derived from Tripterygium wilfordii, has been shown to have excellent antitumor activity, but its poor solubility and severe organ toxicity side effects have hampered its clinical application. METHODS: In this study, a self-assembled nanodrug (PLC-NP) was designed to deliver celastrol to tumor sites while efficiently reducing its side effects by conjugating celastrol with the bioactive material LMWH and P-selectin targeting peptide (PSN). Extensive in vitro and in vivo experiments were performed to investigate both therapeutic efficacy and adverse effects. Furthermore, the specific mechanism of the antitumor activity has also been explored. FINDING: The PLC-NP nanodrugs were spherical in shape, with a mean particle size of 115.83 ± 6.93 nm. PLC-NP was sufficiently stable during blood circulation, with a selective target to P-selectin-highly expressed tumor cells, followed by releasing the containing celastrol under acidic environment and high levels of esterase in tumor cells. Both in vitro and in vivo results confirmed that celastrol's antitumor and anti-metastatic abilities were not attenuated and were actually strengthened after being formed into nanodrugs. More importantly, the organ toxicities of the modified celastrol nanodrug were dramatically reduced. Mechanistic study indicated that the inactivation of PI3K/Akt/mTOR signaling pathway and ROS-mediated mitochondrial dysfunction play critical roles in celastrol-mediated autophagy and apoptosis. INTERPRETATION: Our findings could offer a potential strategy for the translation of toxic compounds into clinical therapeutic nanomedicine. FUNDING: See a detailed list of funding bodies in the Acknowledgements section at the end of the manuscript.


Asunto(s)
Enfermedad Hepática Inducida por Sustancias y Drogas , Nanopartículas , Neoplasias , Triterpenos , Humanos , Triterpenos/farmacología , Selectina-P , Fosfatidilinositol 3-Quinasas/metabolismo , Heparina de Bajo-Peso-Molecular/farmacología , Neoplasias/tratamiento farmacológico , Nanopartículas/uso terapéutico , Apoptosis
13.
Biosens Bioelectron ; 236: 115441, 2023 Sep 15.
Artículo en Inglés | MEDLINE | ID: mdl-37271097

RESUMEN

CdIn2S4 is an interesting ternary metal sulfide whose narrow band gap and tunable optical properties offer new opportunities for the development of novel ECL emitters. Here, we use a simple hydrothermal synthesis to obtain hollow spindle CdIn2S4 (S-CIS), which exhibits strong near-infrared electrochemiluminescence (ECL) emission with K2S2O8 as a coreactant at a low excitation potential (-1.3 V), which is encouraging. The lower excitation potential of S-CIS is probably due to the low band gap energy, which makes the excitation potential positively shift. This lower excitation potential reduces the side-reactions caused by high voltages, effectively avoiding irreversible damage to biomolecules, and protecting the biological activity of antigens and antibodides. In this work, new features of S-CIS in ECL studies are also presented, demonstrating that the ECL emission mechanism of S-CIS is generated by surface state transitions and that S-CIS exhibits excellent near-infrared (NIR) characteristics. Importantly, we introduced S-CIS into electrochemical impedance spectroscopy (EIS) and ECL to the construct a dual-mode sensing platform to achieve AFP detection. The two models with intrinsic reference calibration and high accuracy showed outstanding analytical performance in AFP detection. The detection limits were 0.862 pg mL-1 and 16.8 fg mL-1, respectively. This study demonstrates the key role and great application potential of S-CIS as a novel NIR emitter with easy preparation, low cost and great performance in the development of a simple, efficient and ultrasensitive dual-mode response sensing platform for early clinical use.


Asunto(s)
Técnicas Biosensibles , Técnicas Electroquímicas , Técnicas Electroquímicas/métodos , alfa-Fetoproteínas , Mediciones Luminiscentes/métodos , Técnicas Biosensibles/métodos , Antígenos , Límite de Detección
14.
Anal Chim Acta ; 1272: 341476, 2023 Sep 01.
Artículo en Inglés | MEDLINE | ID: mdl-37355320

RESUMEN

In this study, a novel dual-mode aptamer sensor was developed using Fca-DNA2 as the quenching electrochemiluminescence (ECL) and electrochemical (EC) signal response probe, and Ru-MOF/Cu@Au NPs were used as the ECL substrate platform to detect Alternariol (AOH) via a competitive reaction between AOH and Fca-DNA2. Compared with the conventional aptamer sensor with a single detection signal, this dual-mode aptamer sensor has the following advantages: (1) Electrodeposition-based rapid synthesis Ru-MOF on the electrode surface. (2) The Signal amplification substance Cu@Au NPs can synergistically catalyze Triethanolamine (TEOA) to amplify ECL behavior. (3) The aptamer sensor employs the dual-functional material Fca, which can detect both ECL and EC signals, increasing the result accuracy. Both ECL and EC methods have excellent detection performance for AOH in the detection range of 0.1 pg/mL to 100 ng/mL, with detection limits of 0.014 and 0.083 pg/mL, respectively, and are expected to be used for sensitive AOH detection in real samples.


Asunto(s)
Aptámeros de Nucleótidos , Técnicas Biosensibles , Nanopartículas del Metal , Metalocenos , Técnicas Biosensibles/métodos , Mediciones Luminiscentes/métodos , Técnicas Electroquímicas/métodos , ADN , Aptámeros de Nucleótidos/química , Nanopartículas del Metal/química
15.
J Colloid Interface Sci ; 645: 997-1004, 2023 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-37183158

RESUMEN

The improvement of electrochemiluminescence (ECL) intensity in luminol, a classic electrochemiluminescent material, remains a controversial topic. In this study, synthesis of acetylene black oxide (ACETO) through simple air annealing was successful in introducing oxygen-containing groups and defects, which can act as active sites for the oxygen reduction reaction (ORR) and exhibit excellent catalytic activity. By introducing the two-electron (2e-) ORR into the cathode ECL system of luminol, integration of ACETO and luminol allows for in situ generation of dissolved oxygen into reactive oxygen species (ROS), thereby enhancing the ECL intensity of luminol. It is worth noting that iron-nitrogen-carbon (FeNC), as a secondary antibody (Ab2) label, can catalyze the decomposition of H2O2, the product of 2e- ORR, into ROS to achieve ECL amplification. Alpha-fetoprotein (AFP), an important tumor marker, was successfully detected with a detection limit of 0.01 pg/mL, indicating that this ECL signal amplification strategy has broad application prospects in biological analysis.


Asunto(s)
Técnicas Biosensibles , Nanopartículas del Metal , Luminol/química , Peróxido de Hidrógeno , Especies Reactivas de Oxígeno , Temperatura , Nanopartículas del Metal/química , Mediciones Luminiscentes , Técnicas Electroquímicas , Electrodos , Límite de Detección , Alquinos
16.
Talanta ; 261: 124669, 2023 Aug 15.
Artículo en Inglés | MEDLINE | ID: mdl-37210917

RESUMEN

Alpha-fetoprotein (AFP) is the best diagnostic marker for hepatocellular carcinoma (HCC) and plays an important role in the general surveillance of the population. Therefore, the establishment of an ultra-sensitive AFP assay is essential for the early screening and clinical diagnosis of HCC. In this work, we designed a signal-off biosensor for ultra-sensitive detection of AFP based on an electrochemiluminescent resonance energy transfer (ECL-RET) strategy using luminol intercalated layered bimetallic hydroxide (Luminol-LDH) as an ECL donor and Pt nanoparticles-grown on copper sulfide nanospheres (CuS@Pt) as ECL acceptor. The (Au NPs/Luminol-LDH)n multilayer nanomembrane synthesized by our intercalation and layer-by-layer electrostatic assembly process not only effectively immobilizes luminol but also significantly enhances the ECL signal. The CuS@Pt composite has well visible light absorption ability and can burst the light emitted from luminol by ECL-RET. The biosensor showed good linearity in the range from 10-5 ng mL-1 to 100 ng mL-1 and a minimum detection limit of 2.6 fg mL-1. Therefore, the biosensor provides a novel and efficient strategy for the detection of AFP, which is important for the early screening and clinical diagnosis of HCC.


Asunto(s)
Técnicas Biosensibles , Carcinoma Hepatocelular , Neoplasias Hepáticas , Nanopartículas del Metal , Humanos , Luminol , alfa-Fetoproteínas , Carcinoma Hepatocelular/diagnóstico , Neoplasias Hepáticas/diagnóstico , Mediciones Luminiscentes , Transferencia de Energía , Técnicas Electroquímicas , Límite de Detección , Oro
17.
Anal Chim Acta ; 1257: 341143, 2023 May 29.
Artículo en Inglés | MEDLINE | ID: mdl-37062562

RESUMEN

Effective signal amplification is a prerequisite for ultrasensitive detection by electrochemical immunosensors. For quantitative and ultrasensitive detection of alpha-fetoprotein (AFP), we designed a competitive electrochemical immunosensor and transferred the immunoreactivity from the electrode surface to the cuvette. AFP antigen was captured using AFP primary antibody (Ab1) immobilized on magnetic nanobeads (MBs), and ZIF-8 nanomaterials attached to secondary antibody (Ab2) were used as probes. MBs helped retain the sandwich structure in the test tube through incubation and washing steps. Then, an appropriately fixed excess of sodium ethylenediaminetetraacetic acid (EDTA) solution was added to the cuvettes, resulting in etching of Zn ions from ZIF-8 and formation of Zn-EDTA complexes. After magnetic separation, a certain amount of supernatant is added dropwise to the Prussian blue (PB)-modified electrode (GCE), and Fe ions (from PB) complex with the remaining EDTA in the supernatant, thus reducing the signal response value of PB. The higher the AFP concentration, the lower the amount of free EDTA in the supernatant, the less the destruction of PB, and therefore the higher the current. Under optimal conditions, the immunosensor achieved ultra-sensitive detection of AFP in the range of 10-4 ng/mL-100 ng/mL with a limit of detection (LOD) as low as 0.032 pg/mL (S/N = 3). The excellent performance provides an important tool for the early screening and detection of AFP.


Asunto(s)
Técnicas Biosensibles , Nanopartículas del Metal , alfa-Fetoproteínas , Técnicas Biosensibles/métodos , Ácido Edético , Inmunoensayo/métodos , Límite de Detección , Técnicas Electroquímicas/métodos , Oro/química , Nanopartículas del Metal/química
18.
Anal Chem ; 95(18): 7109-7117, 2023 05 09.
Artículo en Inglés | MEDLINE | ID: mdl-37098252

RESUMEN

In this paper, a novel donor-acceptor pair was creatively proposed based on the principle of electrochemiluminescence resonance energy transfer (ECL-RET): luminol immobilized on polyethyleneimine (PEI)-functionalized manganese-based single-atom nanozymes (Mn SANE/PEI-luminol, donor) and a PtCu-grafted hollow metal polydopamine framework (PtCu/h-MPF, acceptor). A quenched ECL immunosensor was constructed for the ultrasensitive analysis of carcinoembryonic antigen (CEA). Mn SANE, as an efficient novel coreaction accelerator with the outstanding performance of significantly activating H2O2 to produce large amounts of ROS, was further modified by the coreactant PEI, which efficiently immobilized luminol to form a self-enhanced emitter. As a result, the electron transport distance was effectively shortened, the energy loss was reduced, and luminol achieved a high ECL efficiency. More importantly, PtCu-grafted h-MPF (PtCu/h-MPF) was proposed as a novel quencher. The UV-vis spectra of PtCu/h-MPF partially overlap with the ECL spectra of Mn SANE/PEI-luminol, which can effectively trigger the ECL-RET behavior between the donor and the acceptor. The multiple quenching effect on Mn SANE/PEI-luminol was achieved, which significantly improved the sensitivity of the immunosensor. The prepared immunosensor exhibited good linearity in the concentration range of 10-5 to 80 ng/mL. The results indicate that this work provides a new method for the early detection of CEA in clinical diagnosis.


Asunto(s)
Técnicas Biosensibles , Nanopartículas del Metal , Luminol , Antígeno Carcinoembrionario/análisis , Polietileneimina , Técnicas Biosensibles/métodos , Peróxido de Hidrógeno , Técnicas Electroquímicas/métodos , Mediciones Luminiscentes/métodos , Inmunoensayo/métodos , Límite de Detección
20.
Biomed Mater ; 18(3)2023 04 19.
Artículo en Inglés | MEDLINE | ID: mdl-36917859

RESUMEN

Cu2-xSe nanoparticles (Cu2-xSe NPs) as a new therapeutic drug platform is widely used in disease treatment due to their strong near-infrared optical absorption. In recent years, with their continuous expansion of applications in different fields, their own biological effects have received increasing attention. However, little is known about the effect of Cu2-xSe NPs on cancer cell. In this research, we found that Cu2-xSe NPs inhibited proliferation of HepG2 cells (IC50: 15.91µM) and SMMC-7721 cells (IC50: 43.15µM) and they mainly induced cell cycle arrest at the G2/M phase. Moreover, Cu2-xSe NPs inhibited HepG2 and SMMC-7721 cell migration and lamellopodia formation. Further studies indicated that Cu2-xSe NPs impaired mitochondrial respiration by inhibiting electron transport chain complex activity, thus reducing adenosine triphosphate levels. The insufficient energy supply subsequently impaired actin cytoskeleton assembly, ultimately inhibiting HepG2 and SMMC-7721 cell proliferation and migration. These findings suggest that Cu2-xSe NPs may have potentially antitumor activity, which might provide new insights of NPs into specific cancer treatment.


Asunto(s)
Carcinoma Hepatocelular , Neoplasias Hepáticas , Nanopartículas , Humanos , Neoplasias Hepáticas/tratamiento farmacológico , Nanopartículas/uso terapéutico , Células Hep G2 , Proliferación Celular
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