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1.
Analyst ; 2024 Jun 14.
Artículo en Inglés | MEDLINE | ID: mdl-38874099

RESUMEN

Persistent luminescent nanoparticles (PLNPs) are excellent luminescent materials, and near-infrared PLNPs are efficiently applied for biosensing and bioimaging due to their advantages of no excitation, excellent light stability and long afterglow. However, due to interference from the complex environment within organisms, single-mode imaging methods often face limitations in selectivity, sensitivity, and accuracy. Therefore, it is desirable to construct a dual-mode imaging probe strategy with higher specificity and sensitivity for bioimaging. Magnetic resonance imaging (MRI) has been widely used in the field of bioimaging due to its advantages of high resolution, non-radiation and non-invasiveness. Here, by combining near-infrared PLNPs and manganese dioxide (MnO2) nanosheets, a sensitive and convenient dual-mode "turn on" bioimaging nanoprobe ZGC@MnO2 has been developed for long afterglow imaging and MRI of endogenous hydrogen peroxide (H2O2) in the tumor microenvironment (TME). The monitoring of H2O2 has garnered significant attention due to its crucial role in human pathologies. For the dual-mode "turn on" bioimaging nanoprobe, the near-infrared PLNPs of quasi-spherical ZnGa2O4:Cr (ZGC) nanoparticles were synthesized as luminophores, and MnO2 nanosheets were utilized as a fluorescence quencher, carrier and H2O2 recognizer. H2O2 in the TME could reduce MnO2 nanosheets to Mn2+ for MRI, and ZGC nanoparticles were released for long afterglow imaging. Finally, the ZGC@MnO2 nanoprobe exhibited a rapid response, an excellent signal-to-noise ratio and a limit of detection of 3.67 nM for endogenous H2O2 in the TME. This dual-mode approach enhances the detection sensitivity for endogenous H2O2, thereby facilitating the research of endogenous H2O2-associated diseases and clinical diagnostics.

2.
J Infect ; 89(1): 106181, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38744376

RESUMEN

BACKGROUND: Severe fever with thrombocytopenia syndrome (SFTS) is an emerging viral hemorrhagic fever with high fatality rates. The blockade of pro-inflammatory cytokines presents a promising therapeutic strategy. METHODS: We conducted a randomized clinical trial at the 154th hospital, Xinyang, Henan Province. Eligible patients with severe SFTS disease were randomly assigned in a 1:2 ratio to receive either a single intravenous infusion of tocilizumab plus usual care; or usual care only. The primary outcome was the clinical status of death/survival at day 14, while secondary outcomes included improvement from baseline in liver and kidney damage and time required for hospital discharge. The efficacy of tocilizumab plus corticosteroid was compared to those receiving corticosteroid alone. The trial is registered with the Chinese Clinical Trial Registry website (ChiCTR2300076317). RESULTS: 63 eligible patients were assigned to the tocilizumab group and 126 to the control group. The addition of tocilizumab to usual care was associated with a reduced death rate (9.5%) compared to those received only usual care (23.0%), with an adjusted hazard ratio (aHR) of 0.37 (95% confidence interval [CI], 0.15 to 0.91, P = 0.029). Combination therapy of tocilizumab and corticosteroids was associated with a significantly reduced fatality (aHR, 0.21; 95% CI, 0.08 to 0.56; P = 0.002) compared to those receiving corticosteroids alone. CONCLUSIONS: A significant benefit of reducing fatality in severe SFTS patients was observed by using tocilizumab. A combined therapy of tocilizumab plus corticosteroids was recommended for the therapy of severe SFTS.


Asunto(s)
Corticoesteroides , Anticuerpos Monoclonales Humanizados , Quimioterapia Combinada , Síndrome de Trombocitopenia Febril Grave , Humanos , Anticuerpos Monoclonales Humanizados/uso terapéutico , Anticuerpos Monoclonales Humanizados/administración & dosificación , Masculino , Femenino , Persona de Mediana Edad , Síndrome de Trombocitopenia Febril Grave/tratamiento farmacológico , Síndrome de Trombocitopenia Febril Grave/mortalidad , Corticoesteroides/uso terapéutico , Corticoesteroides/administración & dosificación , Anciano , Resultado del Tratamiento , Hospitalización/estadística & datos numéricos , China , Adulto
3.
Anal Chem ; 96(17): 6674-6682, 2024 Apr 30.
Artículo en Inglés | MEDLINE | ID: mdl-38642044

RESUMEN

Photodynamic therapy (PDT) is a significant noninvasive therapeutic modality, but it is often limited in its application due to the restricted tissue penetration depth caused by the wavelength limitations of the light source. Two-photon (TP) fluorescence techniques are capable of having an excitation wavelength in the NIR region by absorbing two NIR photons simultaneously, which offers the potential to achieve higher spatial resolution for deep tissue imaging. Thus, the adoption of TP fluorescence techniques affords several discernible benefits for photodynamic therapy. Organic TP dyes possess a high fluorescence quantum yield. However, the biocompatibility of organic TP dyes is poor, and the method of coating organic TP dyes with silica can effectively overcome the limitations. Herein, based on the TP silica nanoparticles, a functionalized intelligent biogenic missile TP-SiNPs-G4(TMPyP4)-dsDNA(DOX)-Aptamer (TGTDDA) was developed for effective TP bioimaging and synergistic targeted photodynamic therapy and chemotherapy in tumors. First, the Sgc8 aptamer was used to target the PTK7 receptor on the surface of tumor cells. Under two-photon light irradiation, the intelligent biogenic missile can be activated for TP fluorescence imaging to identify tumor cells and the photosensitizer assembled on the nanoparticle surface can be activated for photodynamic therapy. Additionally, this intelligent biogenic missile enables the controlled release of doxorubicin (DOX). The innovative strategy substantially enhances the targeted therapeutic effectiveness of cancer cells. The intelligent biogenic missile provides an effective method for the early detection and treatment of tumors, which has a good application prospect in the real-time high-sensitivity diagnosis and treatment of tumors.


Asunto(s)
Imagen Óptica , Fotoquimioterapia , Fotones , Fármacos Fotosensibilizantes , Humanos , Animales , Fármacos Fotosensibilizantes/química , Fármacos Fotosensibilizantes/farmacología , Fármacos Fotosensibilizantes/uso terapéutico , Ratones , Nanopartículas/química , Doxorrubicina/química , Doxorrubicina/farmacología , Doxorrubicina/uso terapéutico , Dióxido de Silicio/química , Aptámeros de Nucleótidos/química , Colorantes Fluorescentes/química , Neoplasias/tratamiento farmacológico , Neoplasias/diagnóstico por imagen , Antineoplásicos/química , Antineoplásicos/farmacología , Ratones Desnudos , Línea Celular Tumoral , Ratones Endogámicos BALB C
4.
J Pept Sci ; 30(7): e3572, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38396336

RESUMEN

Hairy tofu is a famous Chinese snack that is made from soybeans and rich in various nutrients. In order to further explore the antioxidant peptides of hairy tofu hydrolysates, seven proteases were used to hydrolyze hairy tofu. The results of in vitro radical scavenging activity showed that hairy tofu hydrolysates obtained by pancreatin exhibited the highest antioxidant activity. After Sephadex G-25 gel filtration and reversed-phase high-performance liquid chromatography (RP-HPLC), 97 peptides were identified in the most antioxidant fraction using liquid chromatography-mass spectrometry/mass spectrometry (LC-MS/MS). Among them, nine peptides were synthesized and their antioxidant activities were assessed using a H2O2-induced oxidative 293T cell model. Finally, four peptides (QCESHK, LAWNEGR, NLQGENEWDQK, and FTEMWR) at concentrations of < 50 µg/ml significantly decreased the malondialdehyde content compared with the model group, displaying in vivo antioxidant activity and low cytotoxicity. Overall, this research provided the choice of using hairy tofu peptides as antioxidant products in the pharmaceutical and food industries.


Asunto(s)
Antioxidantes , Péptidos , Humanos , Antioxidantes/química , Antioxidantes/farmacología , Cromatografía Líquida de Alta Presión , Células HEK293 , Peróxido de Hidrógeno , Hidrólisis , Péptidos/química , Péptidos/farmacología , Péptidos/aislamiento & purificación , Alimentos de Soja/análisis
5.
Analyst ; 149(3): 807-814, 2024 Jan 29.
Artículo en Inglés | MEDLINE | ID: mdl-38116839

RESUMEN

The discovery of reliable biomarkers is essential for early diagnosis, treatment, and prognosis assessment of diseases. Many research studies have shown that circRNA is a potential biomarker for diagnosis and prognosis of diseases. However, in situ monitoring circRNA in live cells is still a challenge at present, which brings a major limitation to the development and verification of circRNA as a disease biomarker. In this study, a catalytic hairpin assembly (CHA) reaction-based DNA octahedral amplifier (DOA) was developed for fluorescence resonance energy transfer (FRET) detection and bioimaging of circRNA in living cells. The DOA was first produced by self-assembling a DNA octahedron with six customized single-stranded DNAs, and two hairpins H1 (Cy3) and H2 (Cy5) were then hybridized to four vertices of the DNA octahedron. Idiopathic pulmonary fibrosis (IPF)-related circHIPK3 was used as the target. Once the CHA reaction from H1 and H2 on DOA was activated by a sequence-specific back-splice junction (BSJ) of circHIPK3, a significant FRET signal can be obtained from Cy3 to Cy5. The circHIPK3 was subsequently released to cause the next CHA reaction. Because the DOA has the advantages of the spatial-confinement effect, resistance to nuclease degradation and easy penetration into cells, rapid and excellent signal amplification FRET detection and bioimaging of endogenous circHIPK3 can be achieved in various cells. This study provides a high-precision assay platform to explore the possibility of using circRNA as a biomarker, and it is valuable for circRNA-related early diagnosis and treatment of diseases.


Asunto(s)
Técnicas Biosensibles , Carbocianinas , MicroARNs , MicroARNs/genética , ARN Circular/genética , ADN/genética , Biomarcadores , Técnicas Biosensibles/métodos , Límite de Detección
6.
Analyst ; 148(23): 5963-5971, 2023 Nov 20.
Artículo en Inglés | MEDLINE | ID: mdl-37867382

RESUMEN

Rapid, simultaneous, and sensitive detection of biomolecules has important application prospects in disease diagnosis and biomedical research. However, because the content of intracellular endogenous target biomolecules is usually very low, traditional detection methods can't be used for effective detection and imaging, and to enhance the detection sensitivity, signal amplification strategies are frequently required. The hybridization chain reaction (HCR) has been used to detect many disease biomarkers because of its simple operation, good reproducibility, and no enzyme involvement. Although HCR signal amplification methods have been employed to detect and image intracellular biomolecules, there are still false positive signals. Therefore, a target-triggered enzyme-free amplification system (GHCR system) was developed, as a fluorescent AND-gated sensing platform for intracellular target probing. The false positive signals can be well avoided and the accuracy of detection and imaging can be improved by using the design of the AND gate. Two cancer markers, GSH and miR-1246, were used as two orthogonal inputs for the AND gated probe. The AND-gated probe only works when GSH and miR-1246 are the inputs at the same time, and FRET signals can be the output. In addition to the use of AND-gated imaging, FRET-based high-precision ratiometric fluorescence imaging was employed. FRET-based ratiometric fluorescent probes have a higher ability to resist interference from the intracellular environment, they can avoid false positive signals well, and they are expected to have good specificity. Due to the advantages of HCR, AND-gated, and FRET fluorescent probes, the GHCR system exhibited highly efficient AND-gated FRET bioimaging for intracellular endogenous miRNAs with a lower detection limit of 18 pM, which benefits the applications of ratiometric intracellular biosensing and bioimaging and offers a novel concept for advancing the diagnosis and therapeutic strategies in the field of cancer.


Asunto(s)
Investigación Biomédica , MicroARNs , Neoplasias , Humanos , Colorantes Fluorescentes , Reproducibilidad de los Resultados , MicroARNs/genética , Neoplasias/diagnóstico por imagen
7.
EBioMedicine ; 96: 104807, 2023 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-37738834

RESUMEN

BACKGROUND: Optimal treatment strategy for severe fever with thrombocytopenia syndrome (SFTS) remained unknown. We aimed to evaluate the efficacy of intravenous immunoglobulin (IVIG) on SFTS. METHODS: A retrospective cohort study was conducted based on medical records of the laboratory-confirmed SFTS patients hospitalized during 2010-2020 in the 154th hospital, China. A 1:1 propensity score matching with age, sex, the interval from symptom onset to admission, presence of chronic viral hepatitis, diabetes and disease severity was performed between Non-IVIG group (supportive therapy) and IVIG group (IVIG plus supportive therapy). The matching variables were adjusted to compare the case fatality rates (CFRs), viral load and laboratory parameters between the two groups. Risk ratio (RR) and 95% confidence interval (CI) were reported. FINDINGS: Totally 2219 SFTS patients were recruited. CFRs were significantly higher in 1051 patients in IVIG group than 1168 patients in Non-IVIG group (19.0% vs. 4.6%, RR = 4.30, 95% CI 3.12-5.93). The difference remained significant after matching (17.2% vs. 5.1%, RR = 4.02, 95% CI 2.71-5.97). The CFR of IVIG group was significantly higher in all age groups, two IVIG therapy delay groups and two therapy duration groups compared to that of Non-IVIG group (all P < 0.05). IVIG therapy was related to higher viral loads and reduced counts of lymphocytes, T cells, CD4+ T cells and natural killer cells in the blood (all P < 0.05). INTERPRETATION: No obvious efficacy of IVIG in saving life or improving outcome of SFTS was observed. Caution is needed for clinical physicians to continue prescribing IVIG for SFTS patients. FUNDING: Natural Science Foundation of China.

8.
Anal Chem ; 95(40): 14925-14933, 2023 Oct 10.
Artículo en Inglés | MEDLINE | ID: mdl-37769239

RESUMEN

Bioimaging is widely used in various fields of modern medicine. Fluorescence imaging has the advantages of high sensitivity, high selectivity, noninvasiveness, in situ imaging, and so on. However, one-photon (OP) fluorescence imaging has problems, such as low tissue penetration depth and low spatiotemporal resolution. These disadvantages can be solved by two-photon (TP) fluorescence imaging. However, TP imaging still uses fluorescence intensity as a signal. The complexity of organisms will inevitably affect the change of fluorescence intensity, cause false-positive signals, and affect the accuracy of the results obtained. Fluorescence lifetime imaging (FLIM) is different from other kinds of fluorescence imaging, which is an intrinsic property of the material and independent of the material concentration and fluorescence intensity. FLIM can effectively avoid the fluctuation of TP imaging based on fluorescence intensity and the interference of autofluorescence. Therefore, based on silica-coated gold nanoclusters (AuNCs@SiO2) combined with nucleic acid probes, the dual-mode nanoprobe platform was constructed for TP and FLIM imaging of intracellular endogenous miRNA-21 for the first time. First, the dual-mode nanoprobe used a dual fluorescence quencher of BHQ2 and graphene oxide (GO), which has a high signal-to-noise ratio and anti-interference. Second, the dual-mode nanoprobe can detect miR-21 with high sensitivity and selectivity in vitro, with a detection limit of 0.91 nM. Finally, the dual-mode nanoprobes performed satisfactory TP fluorescence imaging (330.0 µm penetration depth) and FLIM (τave = 50.0 ns) of endogenous miR-21 in living cells and tissues. The dual-mode platforms have promising applications in miRNA-based early detection and therapy and hold much promise for improving clinical efficacy.

9.
Int J Infect Dis ; 134: 95-98, 2023 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-37247691

RESUMEN

OBJECTIVES: Severe fever with thrombocytopenia syndrome (SFTS) virus (SFTSV) is an emerging tick-borne bunyavirus with a high pathogenicity. Little is known about the longitudinal dynamics of the SFTSV-specific neutralizing antibody (NAb) and the related factors in patients with SFTS. METHODS: A prospective cohort study of patients with laboratory-confirmed SFTS were conducted. Antiglomerulonephritis-immunoglobulin G (anti-Gn-IgG) and NAb titers were examined in serially collected serum samples, and their dynamic features were analyzed. RESULTS: NAb was initially detected at 15 days after symptom onset in surviving patients with SFTS, with positive rates of 37.21% (16/43), whereas neither anti-Gn-IgG antibody nor NAb was detected in patients with fatal SFTS during their hospitalization. The NAb levels reached the peak at 2 months after symptom onset, and then gradually declined, with a rapid downward trend from 6 months to 4 years and a relatively slow downward trend from 5 to 10 years. There was a positive correlation between NAb and anti-Gn-IgG titers in surviving patients with SFTS (r = 0.699, P <0.001). Patients with a mild illness or low viral load experienced early NAb seroconversion. Six different dynamic patterns of NAb were noted in surviving patients. CONCLUSION: These data provide useful information regarding the dynamic changes in NAb in patients with SFTS during the acute and convalescent phases and the follow-up period.


Asunto(s)
Infecciones por Bunyaviridae , Phlebovirus , Síndrome de Trombocitopenia Febril Grave , Humanos , Anticuerpos Neutralizantes , Estudios Prospectivos , Anticuerpos Antivirales , Inmunoglobulina G
10.
Analyst ; 148(5): 1093-1101, 2023 Feb 27.
Artículo en Inglés | MEDLINE | ID: mdl-36722984

RESUMEN

The rapid, simultaneous, sensitive detection of the targets has important application prospects for disease diagnosis and biomedical studies. However, in practical applications, the content of the targets is usually very low, and signal amplification strategies are often needed to improve the detection sensitivity. DNAzyme-driven DNA walkers are an excellent signal amplification strategy due to their outstanding specificity and sensitivity. Food-borne pathogens have always been a foremost threat to human health, and it is an urgent demand to develop a simple, rapid, sensitive, and portable detection method for food-borne pathogens. In addition, there are various species of pathogens, and it is difficult to simultaneously detect multiple pathogens by a single DNA walker. For this reason, a substrate strand with three rA cleavage sites was cleverly designed, and a multivalent DNA walker sensor combined with the microfluidic chip technology was proposed for the simultaneous, rapid, sensitive analysis of Vibrio parahaemolyticus, Salmonella typhimurium, and Staphylococcus aureus. The developed sensor could be used to detect pathogens simultaneously and efficiently with low detection limits and wide detection ranges. Moreover, the combination of gold stirring rod enrichment and DNA walker achieved double amplification, which greatly improved the detection sensitivity. More importantly, by changing the design of the substrate chain, the sensor was expected to be used to detect other targets, thus broadening the scope of practical applications. Therefore, the sensor can build novel detection tool platforms in the field of biosensing.


Asunto(s)
Técnicas Biosensibles , Microfluídica , Humanos , Técnicas de Amplificación de Ácido Nucleico/métodos , Técnicas Biosensibles/métodos , ADN/genética , ADN/química , Análisis de Secuencia por Matrices de Oligonucleótidos , Límite de Detección
11.
Int J Infect Dis ; 123: 80-83, 2022 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-35987469

RESUMEN

Severe fever with thrombocytopenia syndrome (SFTS), an emerging infectious disease with high mortality, was first reported in 2009 in China and subsequently endemic to South Korea, Japan, Vietnam, and Myanmar. This disease is transmitted predominantly by tick bites and potentially human-to-human. Personal protective equipments (PPEs) have been recommended to prevent SFTS human-to-human transmission, whereas the specific use of PPEs and the effect on viral transmission have rarely been reported. This report identified a family cluster of six patients with SFTS virus (SFTSV) infection. All five secondary patients had been wearing gloves and masks when exposed to the blood of the index patient, but none of them wore goggles or face shields for eye protection. Ocular route was suggested as a highly possible mode for SFTSV transmission through epidemiological, serological, and phylogenetic analysis. Eye protection should be stressed for clinicians when exposed to blood or bloody secretions.


Asunto(s)
Infecciones por Bunyaviridae , Phlebovirus , Síndrome de Trombocitopenia Febril Grave , China/epidemiología , Humanos , Equipo de Protección Personal , Phlebovirus/genética , Filogenia , República de Corea/epidemiología
12.
J Med Virol ; 94(12): 5933-5942, 2022 12.
Artículo en Inglés | MEDLINE | ID: mdl-36030552

RESUMEN

Severe fever with thrombocytopenia syndrome (SFTS) is an emerging tick-borne disease with a high case fatality rate. Few studies have been performed on bacterial or fungal coinfections or the effect of antibiotic therapy. A retrospective, observational study was performed to assess the prevalence of bacterial and fungal coinfections in patients hospitalized for SFTSV infection. The most commonly involved microorganisms and the effect of antimicrobial therapy were determined by the site and source of infection. A total of 1201 patients hospitalized with SFTSV infection were included; 359 (29.9%) had microbiologically confirmed infections, comprised of 292 with community-acquired infections (CAIs) and 67 with healthcare-associated infections (HAIs). Death was independently associated with HAIs, with a more significant effect than that observed for CAIs. For bacterial infections, only those acquired in hospitals were associated with fatal outcomes, while fungal infection, whether acquired in hospital or community, was related to an increased risk of fatal outcomes. The infections in the respiratory tract and bloodstream were associated with a higher risk of death than that in the urinary tract. Both antibiotic and antifungal treatments were associated with improved survival for CAIs, while for HAIs, only antibiotic therapy was related to improved survival, and no effect from antifungal therapy was observed. Early administration of glucocorticoids was associated with an increased risk of HAIs. The study provided novel clinical and epidemiological data and revealed risk factors, such as bacterial coinfections, fungal coinfections, infection sources, and treatment strategies associated with SFTS deaths/survival. This report might be helpful in curing SFTS and reducing fatal SFTS.


Asunto(s)
Infecciones por Bunyaviridae , Coinfección , Phlebovirus , Síndrome de Trombocitopenia Febril Grave , Antibacterianos/uso terapéutico , Antifúngicos/uso terapéutico , Infecciones por Bunyaviridae/epidemiología , Coinfección/epidemiología , Humanos , Estudios Retrospectivos
13.
Emerg Microbes Infect ; 11(1): 1672-1682, 2022 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-35603493

RESUMEN

Severe fever with thrombocytopenia syndrome virus (SFTSV), an emerging tick-borne bunyavirus, causes mild-to-moderate infection to critical illness or even death in human patients. The effect of virus variations on virulence and related clinical significance is unclear. We prospectively recruited SFTSV-infected patients in a hotspot region of SFTS endemic in China from 2011 to 2020, sequenced whole genome of SFTSV, and assessed the association of virus genomic variants with clinical data, viremia, and inflammatory response. We identified seven viral clades (I-VII) based on phylogenetic characterization of 805 SFTSV genome sequences. A significantly increased case fatality rate (32.9%) was revealed in one unique clade (IV) that possesses a specific co-mutation pattern, compared to other three common clades (I, 16.7%; II, 13.8%; and III, 11.8%). The phenotype-genotype association (hazard ratios ranged 1.327-2.916) was confirmed by multivariate regression adjusting age, sex, and hospitalization delay. We revealed a pronounced inflammation response featured by more production of CXCL9, IL-10, IL-6, IP-10, M-CSF, and IL-1ß, in clade IV, which was also related to severe complications. We observed enhanced cytokine expression from clade IV inoculated PBMCs and infected mice. Moreover, the neutralization activity of convalescent serum from patients infected with one specified clade was remarkably reduced to other viral clades. Together, our findings revealed a significant association between one specific viral clade and SFTS fatality, highlighting the need for molecular surveillance for highly lethal strains in endemic regions and unravelled the importance of evaluating cross-clade effect in development of vaccines and therapeutics.


Asunto(s)
Infecciones por Bunyaviridae , Phlebovirus , Síndrome de Trombocitopenia Febril Grave , Animales , Genómica , Humanos , Ratones , Phlebovirus/fisiología , Filogenia
14.
Chem Commun (Camb) ; 57(80): 10391-10394, 2021 Oct 07.
Artículo en Inglés | MEDLINE | ID: mdl-34542119

RESUMEN

Transferrin-modified AuNCs (Tf-AuNCs) with two photon-near infrared (TP-NIR) fluorescence were prepared. For the first time, a novel nanoprobe platform, Tf-AuNCs@MnO2, was developed for the TP-NIR fluorescence imaging and magnetic resonance imaging of living cells and tissues. This platform had high spatiotemporal resolution and a tissue-penetration depth of 300 µm.


Asunto(s)
Colorantes Fluorescentes/química , Nanopartículas del Metal/química , Transferrina/química , Colorantes Fluorescentes/efectos de la radiación , Fluorometría , Glutatión/análisis , Glutatión/metabolismo , Oro/química , Oro/efectos de la radiación , Humanos , Rayos Infrarrojos , Células MCF-7 , Compuestos de Manganeso/química , Nanopartículas del Metal/efectos de la radiación , Óxidos/química , Fotones
15.
Analyst ; 146(15): 4945-4953, 2021 Jul 26.
Artículo en Inglés | MEDLINE | ID: mdl-34259245

RESUMEN

Two-photon fluorescence imaging is one of the most attractive imaging techniques for monitoring important biomolecules in the biomedical field due to its advantages of low light scattering, high penetration depth, and suppressed photodamage/phototoxicity under near-infrared excitation. However, in actual biological imaging, organic two-photon fluorescent dyes have disadvantages such as high biological toxicity and their fluorescence efficiency is easily affected by the complex environment in organisms. In this study, a novel nanoprobe platform with two-photon dye-doped silica nanoparticles was developed for FRET-based ratiometric biosensing and bioimaging, with endogenous ATP chosen as the target for detection. The nanoprobe has three components: (1) a two-photon dye-doped silica nanoparticle core, which serves as an energy donor for FRET; (2) amino-modified hairpin primers with carboxy fluorescein as an energy acceptor for FRET; (3) an aptamer acting as a recognition unit to realize the probing function. The nanoprobe showed ratiometric fluorescence responses for ATP detection with high sensitivity and high selectivity in vivo. Moreover, the nanoprobe showed satisfactory ratiometric two-photon fluorescence imaging of endogenous ATP in living cells and tissues (penetration depth of 190 nm). These results indicated that novel two-photon silica nanoparticles can be constructed by doping a two-photon fluorescent dye into silica nanoparticles, and they can effectively solve the disadvantages of two-photon fluorescent dyes. These excellent performances indicate that this novel nanoprobe platform will become a very valuable molecular imaging tool, which can be widely used in the biomedical field for drug screening and disease diagnosis and other related research.


Asunto(s)
Nanopartículas , Dióxido de Silicio , Adenosina Trifosfato , Transferencia Resonante de Energía de Fluorescencia , Colorantes Fluorescentes/toxicidad , Nanopartículas/toxicidad , Fotones , Dióxido de Silicio/toxicidad
16.
Chem Commun (Camb) ; 57(51): 6288-6291, 2021 Jun 24.
Artículo en Inglés | MEDLINE | ID: mdl-34075954

RESUMEN

The dual-mode bio-imaging nanoprobe TP-CQDs@MnO2, based on two-photon carbon quantum dots and MnO2, has been developed for the two-photon fluorescence and MR imaging of endogenous H2O2 in the tumor microenvironment, and it achieved high selectivity, a great signal-to-noise ratio, a limit of detection (LOD) of 1.425 pM for H2O2, and a two-photon tissue penetration depth of 280 µm.


Asunto(s)
Peróxido de Hidrógeno/metabolismo , Imagen por Resonancia Magnética , Microscopía Confocal , Nanoestructuras/química , Carbono/química , Línea Celular , Medios de Contraste/química , Humanos , Peróxido de Hidrógeno/análisis , Límite de Detección , Compuestos de Manganeso/química , Óxidos/química , Puntos Cuánticos/química , Relación Señal-Ruido , Espectrometría de Fluorescencia , Microambiente Tumoral
17.
Anal Chem ; 93(14): 5691-5699, 2021 04 13.
Artículo en Inglés | MEDLINE | ID: mdl-33779144

RESUMEN

Biological fluorescence imaging technologies have attracted a lot of attention and have been widely used in biomedical fields. Compared with other technologies, fluorescence imaging has a lower cost, higher sensitivity, and easier operation. However, due to the disadvantages of one-photon (OP) fluorescence imaging, such as low spatial and poor temporal resolution and poor tissue permeability depth, the application of OP fluorescence imaging has some limitations. Though two-photon (TP) fluorescence imaging can well overcome these shortcomings of OP, the single-mode imaging remains deficient. Therefore, dual-mode imaging combined with TP imaging and magnetic resonance imaging (MRI) can make up for the deficiency well, which make dual-mode imaging for the early diagnosis of diseases more accurate. Hence, a dual-mode nanoprobe TP-CQDs@MnO2 was designed for probing the fluorescence/MR dual-mode imaging strategy of intracellular H+ by using TP-CQDs (two photon-carbon quantum dots) and MnO2 nanosheets. The MnO2 nanosheets treated as fluorescence quenching agents of TP-CQDs exhibited a supersensitive response to H+, which made the fluorescence signals turn "off" to "on" for TP fluorescence imaging, in the meantime, large amounts of Mn2+ were generated for MRI. A dual-mode nanoprobe TP-CQDs@MnO2 can monitor intracellular wide pH (4.0-8.0), and the fluorescence intensity of TP-CQDs@MnO2 has recovered up to more than six times and the corresponding results of MRI were satisfactory. TP fluorescence imaging of cells and tissues showed higher detection sensitivity and deeper tissue penetration (240.0 µm) than OP. The dual-mode imaging platform hold great promise for pH-related early diagnosis and treatment, which has great potential to improve clinical efficacy.


Asunto(s)
Compuestos de Manganeso , Puntos Cuánticos , Concentración de Iones de Hidrógeno , Imagen por Resonancia Magnética , Imagen Óptica , Óxidos
18.
Angew Chem Int Ed Engl ; 60(22): 12569-12576, 2021 05 25.
Artículo en Inglés | MEDLINE | ID: mdl-33739576

RESUMEN

The novel theranostic nanosystems based on two-photon fluorescence can achieve higher spatial resolution of deep tissue imaging for simultaneous diagnosis and therapy of a variety of cancers. Herein, we have designed and prepared FRET-based two-photon mesoporous silica nanoparticles (MTP-MSNs) for single-excitation multiplexed intracellular imaging and targeted cancer therapy for the first time. This nanosystem includes two constituents, containing (1) multicolor two-photon mesoporous silica nanoparticles and (2) cancer cell-targeting aptamers that act as gatekeepers for MTP-MSNs. After incubation with cancer cells, the Dox-loaded and aptamer-capped MTP-MSNs could be internalized into the cells, opening the pores and releasing the drug. Furthermore, using two-photon multicolor fluorescence, MTP-MSNs could serve as good contrast agents for multicolor two-photon intracellular imaging with increased imaging depth and improved spatial localization of tissue. In sum, these multicolor MTP-MSNs provide a promising system for traceable targeted cancer therapy with further applications in multiplex intracellular imaging and the screening of drug.


Asunto(s)
Microscopía de Fluorescencia por Excitación Multifotónica/métodos , Nanopartículas/química , Neoplasias/diagnóstico , Animales , Aptámeros de Nucleótidos/química , Supervivencia Celular/efectos de los fármacos , Medios de Contraste/química , Doxorrubicina/química , Doxorrubicina/farmacología , Doxorrubicina/uso terapéutico , Portadores de Fármacos/química , Transferencia Resonante de Energía de Fluorescencia , Humanos , Rayos Láser , Hígado/efectos de los fármacos , Hígado/patología , Células MCF-7 , Neoplasias/tratamiento farmacológico , Oligodesoxirribonucleótidos/química , Porosidad , Ratas , Dióxido de Silicio/química , Nanomedicina Teranóstica
19.
Talanta ; 220: 121364, 2020 Dec 01.
Artículo en Inglés | MEDLINE | ID: mdl-32928394

RESUMEN

Fluorescence detection technology has been widely concerned for its advantages of low cost, simple operation, good sensitivity, real-time and non-destructive biological imaging. However, most fluorophores emit bright fluorescence in solution, and the fluorescence decreases significantly in the high concentration or solid/aggregated state, which is called aggregation-caused quenching (ACQ). Cysteine (Cys) is an important kind of amino-acid in the field of bio-medicine, whose main function is to participate in metabolism and protein synthesis, detoxification, but intracellular cysteine concentrations (30-200 µM) are much low, and direct detection of endogenous cysteine is hampered by interference with other thiols. To solve the above problems, based on solid-state fluorophore HPQ, we for the first time prepared a novel solid-state fluorescence probe MA-HPQ, for monitoring of endogenous Cys, operated by the mechanism of excited intramolecular proton transfer (ESIPT). MeO-HPQ is completely insoluble in water, has very strong solid-state fluorescence with the maximum emission wavelength of 510 nm and the maximum excitation wavelength of 365 nm. This special property makes it very suitable for confocal microscopy compared with ordinary water-soluble fluorescent dyes. Due to the large Stokes shift (145 nm), MA-HPQ has very desirable advantages: reduced interference of background fluorescence, increased sensitivity, and enhanced contrast of biological imaging. More importantly, by preventing it from establishing internal hydrogen bonds, which is between imine nitrogen and phenolic hydroxyl groups, it can be made insoluble in water and have strong fluorescence properties, and the process is reversible. The ESIPT process can be blocked by masking phenolic hydroxyl, which can inhibit fluorescence to a large extent. In the presence of Cys, the probe reacts, releasing free MeO-HPQ, and begins to form a precipitated solid. The precipitated solid emitted bright green solid-state fluorescence, which was enhanced 43 times more than MA-HPQ. These results indicate that the probe MA-HPQ can be suitable to real spatiotemporal imaging of endogenous cysteine in HeLa cells. The excellent performance of the probe makes it applying for the visualization detection of endogenous cysteine in living cells and tissues with obtaining satisfactory results.


Asunto(s)
Cisteína , Colorantes Fluorescentes , Cisteína/análisis , Células HeLa , Humanos , Protones , Espectrometría de Fluorescencia
20.
Chem Biodivers ; 17(8): e2000268, 2020 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-32533626

RESUMEN

The present study investigated the chemical composition, antioxidant, antimicrobial, and anti-inflammatory activities of essential oil (EO) derived from the wild rhizomes of Atractylodes macrocephala Koidz. (AMA) growing in Qimen County (eastern China). GC/MS analysis identified fifteen compounds, representing 92.55 % of AMA EO. The major compounds were atractylone (39.22 %), ß-eudesmol (27.70 %), thymol (5.74 %), hinesol (5.50 %), and 11-isopropylidenetricyclo[4.3.1.1(2,5)]undec-3-en-10-one (4.71 %). Ferricyanide reducing, 1,1-diphenyl-2-picyrlhydrazyl (DPPH) and 3-ethyl-benzothiazoline-6-sulfonic acid (ABTS) scavenging assays revealed that AMA EO exhibited strong antioxidant capacities. Additionally, AMA EO showed inhibitory effects on growth of Escherichia coli, Pseudomonas aeruginosa, Salmonella enterica, Staphylococcus aureus, and Bacillus subtilis, with the minimum inhibitory concentrations (MIC) ranging from 0.5 to 2.0 mg/mL. Treatments with AMA EO also significantly inhibited nitric oxide (NO) and prostaglandin E2 (PGE2 ) production in lipopolysaccharide-stimulated RAW264.7 cells, indicating anti-inflammatory activity of AMA EO. Furthermore, treatments with AMA EO decreased the transcriptional levels of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2), which might be the molecular mechanisms underlying its anti-inflammatory effects. Overall, these results provide a theoretical basis for further study and application of AMA EO in food and medicine products.


Asunto(s)
Antibacterianos/farmacología , Antiinflamatorios/farmacología , Antioxidantes/farmacología , Atractylodes/química , Aceites Volátiles/farmacología , Rizoma/química , Animales , Cromatografía de Gases y Espectrometría de Masas , Ratones , Pruebas de Sensibilidad Microbiana , Células RAW 264.7
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