RESUMO
More than 55 million people live with dementia worldwide in 2021, and there are nearly 10 million new cases every year. Alzheimer's disease (AD) is the most common cause of dementia. Despite urgent need, early detection of AD and long-term monitoring of AD progression have been challenging. This is due to the limited availability of brain imaging facilities and the highly invasive procedure with the cerebrospinal fluid assay to assess the level of AD biomarkers, such as beta-amyloid (Aß). Reliable measurements of AD biomarkers in blood samples are still difficult because of their very low abundance. Here, we develop a rapid, specific, and ultrasensitive immunoassay using plasmonic-gold nanoisland (pGOLD) chips with near-infrared fluorescence-enhanced detection for Aß1-40 and Aß1-42. We show step-by-step processes and results during the platform establishment, including antibody specificity and sensitivity tests, antibody pair examination, condition optimization, and procedure refinement. Finally, we demonstrate the platform performance with detection sensitivity at the subpicogram per milliliter level. This platform, therefore, has a great application potential for early detection of AD using blood samples.
Assuntos
Doença de Alzheimer/diagnóstico , Peptídeos beta-Amiloides/análise , Materiais Biomiméticos/química , Ouro/química , Nanopartículas Metálicas/química , Doença de Alzheimer/sangue , Humanos , Imunoensaio , Teste de Materiais , Tamanho da PartículaRESUMO
High-throughput and rapid arsenite (As(III)) monitoring is an urgent task to deal with the critical threat from As(III) contamination in the environment. In this study, an effective, portable, and sensitive As(III) assay was developed using the plasmonic silver (pAg) chips for As(III) detection. The pAg chips were fabricated by a simple seed-mediated method to grow the silver nanoisland films (Ag-NIFs) with the compact nanoislands and adjustable interisland gaps on the large-sized substrates. With appropriate surface functionalization and optimal chip manufacturing, Cy7.5 fluorescence dye can be immobilized on the surface of Ag-NIFs in the presence of As(III) to output the enhanced fluorescence signals up to 10-fold and improve the detection limit of As(III) less than 10 ppb. According to our results, the high-throughput detection measurements and wide dynamic range over 4 orders of magnitude implied the broad prospects of pAg chips in fluorescence-enhanced assays. The proposed As(III) assay has shown great opportunities for the practical application of ultratrace As(III) monitoring.
RESUMO
A system comprising a gold nanoisland film (Au NIF) covered with a liquid crystal (LC) material is introduced. By applying a voltage across the LC bulk, we demonstrate that changes in the refractive-index and orientation significantly modified the hybrid plasmonic-photonic resonances of the Au NIF. The hybrid structure enabled active control of the spectrum of the resonance wavelength of the metallic nanoisland by means of an externally applied electric field. Our modeling supports the observed results in LC/Au NIF. In a combination of the nanostructured surface with birefringent LCs, nonpolarized wavelength tunability of ~15 nm and absorbance tunability of ~0.024 were achieved in the visible wavelength, opening the door to optical devices and nanoscale sensors.
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The glucose metabolism rate in cancer cells is a crucial piece of information for the cancer aggressiveness. A feasible method to monitor processes of oncogenic mutations has been demonstrated in this work. The fluorescent gold nanoclusters conjugated with glucose (glucose-AuNCs) were successfully synthesized as a cancer-targeting probe for glucose transporters (Gluts) overexpressed by U-87 MG cancer cells, which can be observed under confocal microscopy. The structural and optical characterizations of fluorescent glucose-AuNCs were confirmed by transmission electron microscope (TEM) and Fourier transform infrared spectroscopy (FTIR). The MTT assay exhibited the high biocompatibility of water-soluble glucose-AuNCs for further biomedical applications. The glucose metabolic cleavage of glucose-AuNCs by glycolytic enzymes from U-87 MG cancer cell was measured by fluorescence change of glucose-AuNCs. The fluorescence change based on the integrated area under fluorescence spectra ( A t) of glucose-AuNCs was plotted as a function of different reaction time ( t) with glycolytic enzymes. The fitted curve of A t versus t showed the first-order kinetics to explain the mechanism of glucose metabolic cleavage rate of glucose-AuNCs by glycolytic enzymes. The rate constant k could be utilized to determine the glucose metabolism rate of glucose-AuNCs for the quantitative analysis of cancer aggressiveness. Our work provides a practical application of target-specific glucose-AuNCs as a fluorescence probe to analyze the glucose metabolism in Gluts overexpressed cancer cells.
Assuntos
Corantes Fluorescentes/química , Proteínas Facilitadoras de Transporte de Glucose/metabolismo , Glucose/metabolismo , Glicólise , Ouro/química , Nanopartículas Metálicas/química , Neoplasias/metabolismo , Técnicas Biossensoriais/métodos , Linhagem Celular Tumoral , Glucose/química , Proteínas Facilitadoras de Transporte de Glucose/análise , Humanos , Microscopia Confocal/métodos , Microscopia de Fluorescência/métodos , Neoplasias/enzimologiaRESUMO
Boron neutron capture therapy is a promising tumor treatment method, though its wide application has been limited due to the poor tumor selectivity and intracellular delivery of 10B-compounds. Here, block copolymer-boron cluster conjugate based on the clinically used sodium borocaptate (BSH) and poly(ethylene glycol)-b-poly(glutamic acid) copolymer have been developed for effectively penetrating tumor tissues and homogeneously delivering the boron clusters into cancer cells towards safe and efficient boron neutron capture therapy. The PEGylated block copolymer-boron cluster (BSH) conjugate has demonstrated significant higher cellular uptake and tumor accumulation when compared to the non-PEGylated formulations and BSH. Moreover, the enhanced delivery to tumors of the conjugates, as well as their superior intratumoral penetration, which facilitated reaching the intracellular space of most cells in tumors, allowed the effective ablation of tumors after neutron irradiation.
Assuntos
Boroidretos/química , Terapia por Captura de Nêutron de Boro/métodos , Sistemas de Liberação de Medicamentos/métodos , Neoplasias/radioterapia , Polietilenoglicóis/química , Ácido Poliglutâmico/química , Compostos de Sulfidrila/química , Animais , Linhagem Celular Tumoral , Sobrevivência Celular , Química Farmacêutica , Liberação Controlada de Fármacos , Feminino , Humanos , Camundongos Endogâmicos BALB C , Camundongos Nus , PermeabilidadeRESUMO
Hydrogen is considered as sustainable and environmentally friendly energy for global energy demands in the future. Here a Co-FeS2 catalyst with surface phosphide doping (P/Co-FeS2 ) for hydrogen evolution reaction (HER) in acidic solutions is developed. The P/Co-FeS2 exhibits superior HER electrochemical performance with overpotential of -90 mV at 100 mA cm-2 and Tafel slope of 41 mV/decade and excellent durability.
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Polyion complex vesicles (PICsomes) are polymeric hollow capsules composed of a unique semipermeable membrane, which may represent a versatile platform for constructing drug-loaded nanoformulation. However, it is difficult to retain water-soluble low-molecular-weight compounds (LMWCs) in the inner space of PICsome because of the high permeability of PIC membrane for LMWCs. Herein, we selected mesoporous silica nanoparticle (MSN) as a drug-retaining nanomatrix, and we demonstrated successful encapsulation of MSN into the PICsome to obtain MSN@PICsome. The efficacy of MSN loading, a ratio of the amount of MSN encapsulated in the PICsome to the amount of feed MSN, was at most 83%, and the diameter of resulting product was approximately 100 nm. The obtained MSN@PICsome was stably dispersed under the physiological condition, and showed considerable longevity in blood circulation of mice. Furthermore, the surface of MSN in MSN@PICsome can be modified without any deterioration of the vesicle structure, obtaining amino-functionalized and sulfonate-functionalized MSN@PICsomes (A-MSN@PICsome and S-MSN@PICsome, respectively). Both surface-modified MSN@PICsomes were successfully loaded with charged water-soluble low-molecular-weight compounds (LMWCs). Particularly, S-MSN@PICsome kept 8 wt % gemcitabine (GEM) per S-MSN, and released it in a sustained manner. GEM-loaded S-MSN@PICsome demonstrated marked cytotoxicity against cultured tumor cells, and achieved significant in vivo efficacy to suppress the growth of subcutaneously implanted lung tumor via intravenous administration.
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Nanomedicines capable of smart operation at the targeted site have the potential to achieve the utmost therapeutic benefits. Providing nanomedicines that respond to endogenous stimuli with an additional external trigger may improve the spatiotemporal control of their functions, while avoiding drawbacks from their inherent tissue distribution. Herein, by exploiting the permeabilization of endosomes induced by photosensitizer agents upon light irradiation, we complemented the intracellular action of polymeric micelles incorporating camptothecin (CPT), which can sharply release the loaded drug in response to the reductive conditions of the cytosol, as an effective strategy for precisely controlling the function of these nanomedicines in vivo, while advancing toward a light-activated chemotherapy. These camptothecin-loaded micelles (CPT/m) were stable in the bloodstream, with minimal drug release in extracellular conditions, leading to prolonged blood circulation and high accumulation in xenografts of rat urothelial carcinoma. With the induction of endosomal permeabilization with the clinically approved photosensitizer, Photofrin, the CPT/m escaped from the endocytic vesicles of cancer cells into the cytosol, as confirmed both in vitro and in vivo by real-time confocal laser microscopies, accelerating the drug release from the micelles only in the irradiated tissues. This spatiotemporal switch significantly enhanced the in vivo antitumor efficacy of CPT/m without eliciting any toxicity, even at a dose 10-fold higher than the maximum tolerated dose of free CPT. Our results indicate the potential of reduction-sensitive drug-loaded polymeric micelles for developing safe chemotherapies after activation by remote triggers, such as light, which are capable of permeabilizing endosomal compartments.
Assuntos
Antineoplásicos Fitogênicos/administração & dosagem , Camptotecina/administração & dosagem , Citosol/metabolismo , Luz , Micelas , Polímeros/química , Animais , Linhagem Celular Tumoral , Oxirredução , RatosRESUMO
In terms of medical techniques, Taiwan has gained international recognition in recent years. However, the medical information system industry in Taiwan is still at a developing stage compared with the software industries in other nations. In addition, systematic development processes are indispensable elements of software development. They can help developers increase their productivity and efficiency and also avoid unnecessary risks arising during the development process. Thus, this paper presents an application of Light-Weight Capability Maturity Model Integration (LW-CMMI) to Chang Gung Medical Research Project (CMRP) in the Nuclear medicine field. This application was intended to integrate user requirements, system design and testing of software development processes into three layers (Domain, Concept and Instance) model. Then, expressing in structural System Modeling Language (SysML) diagrams and converts part of the manual effort necessary for project management maintenance into computational effort, for example: (semi-) automatic delivery of traceability management. In this application, it supports establishing artifacts of "requirement specification document", "project execution plan document", "system design document" and "system test document", and can deliver a prototype of lightweight project management tool on the Nuclear Medicine software project. The results of this application can be a reference for other medical institutions in developing medical information systems and support of project management to achieve the aim of patient safety.
RESUMO
Nowadays, patients usually take more than three drugs for diseases such as hypertension, diabetes, and dyslipidemia. Hence, nuclear medicine physicians should be very careful about the medication history of each patient and ensure that their medication will not cause false positive or false negative imaging results, because either condition will interfere with adequate treatment of the patient and result in a wrong diagnosis. The aim of the present paper is to develop an ontology-based medication search and alert system for scintiphotography of Chang Gung Memorial hospital at Kaohsiung. Composed of four sub-systems, including Medication History Collect Agent (MHCA), Medication History Search System (MHSS), Patient Medication Consultation System (PMCS), and Patient Medication Alert System (PMAS), this medication search and alert system for scintiphotography is expected to support decision making of nuclear medicine examination, improve accuracy of image reading, and offer detailed data for further research. The ultimate goal of this system is to ensure patient safety.
Assuntos
Registros Eletrônicos de Saúde/organização & administração , Anamnese/métodos , Sistemas de Registro de Ordens Médicas/organização & administração , Serviço Hospitalar de Medicina Nuclear/organização & administração , Segurança do Paciente , Humanos , Erros de Medicação/prevenção & controle , Gestão da Segurança/métodosRESUMO
A polymer solar cell based on poly(3-hexylthiophene) (P3HT)/iron disulfide (FeS2) nanocrystal (NC) hybrid is presented. The FeS2 NCs of 10 nm in diameter were homogeneously blended with P3HT to form an active layer of a solar cell. An extended red light harvesting up to 900 nm resulting from the NCs in the device has been demonstrated, compared to a typical absorption edge of 650 nm of a pristine P3HT. The environmentally friendly and low-cost FeS2 NCs can be used as a promising candidate for an acceptor in the polymer solar cell device application with an enhanced photovoltaic response in the extended red light region.