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1.
Chem Commun (Camb) ; 57(94): 12679-12682, 2021 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-34779461

RESUMO

By means of the formation of SeN, the ABT-Se and NDI-Se were developed to detect and visualize endogenous hypobromous acid (HOBr) in live cells. Specifically, the upregulation of HOBr was monitored by NDI-Se during the administration of an immunotherapeutic agent.

2.
Anal Chem ; 93(45): 15088-15095, 2021 11 16.
Artigo em Inglês | MEDLINE | ID: mdl-34729977

RESUMO

Alzheimer's disease (AD) involves multiple pathological factors that mutually cooperate and closely contact to form interaction networks for jointly promoting the AD progression. Therefore, the comonitoring of different factors is particularly valuable for elucidating their level dynamics and complex interactions. However, such significant investigations remain a major challenge due to the lack of unimolecular fluorescent probes capable of simultaneous and discriminative visualization of multiple targets. To address this concern, as proof of principle, we rationally designed a unimolecular fluorescent probe to discriminate and simultaneously profile amyloid-ß (Aß) plaques and peroxynitrite (ONOO-), which are both the pronounced AD pathological factors. Herein, a novel ONOO- reaction trigger was installed onto an Aß plaque binding fluorophore to generate a dual functional fluorescent probe, displaying completely separate spectral responses to Aß plaques and ONOO- with high selectivity and sensitivity. With this probe, for the first time, we comonitored the distribution and variation of Aß plaques and ONOO- through two independent fluorescence channels, demonstrating their close apposition and tight correlation during AD course in live cell and mouse models through two-photon imaging mode. Notably, Aß aggregates induce the neuronal ONOO- generation, which conversely facilitates Aß aggregation. The two critical events, ONOO- stress and Aß aggregation, mutually amplify each other through positive feedback mechanisms and jointly promote the AD onset and progression. Furthermore, by coimaging of the level dynamics of Aß plaques and ONOO-, we found that the cerebral ONOO- is a potential biomarker, which emerges earlier than Aß plaques in transgenic mouse models. Overall, the dual-channel responsive performance renders this probe as a powerful imaging tool to decipher Aß plaque-ONOO- interactions, which will facilitate AD-associated molecular pathogenesis elucidation and multitarget drug discovery.


Assuntos
Doença de Alzheimer , Doença de Alzheimer/diagnóstico por imagem , Peptídeos beta-Amiloides , Animais , Corantes Fluorescentes , Camundongos , Camundongos Transgênicos , Ácido Peroxinitroso , Placa Amiloide/diagnóstico por imagem
3.
Chem Commun (Camb) ; 57(67): 8320-8323, 2021 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-34319334

RESUMO

Herein, a light-activatable photosensitizer based on a diarylethene derivative, DAE-TPE, was developed for photodynamic therapy. Upon UV exposure, the "opened" form (OF) of DAE-TPE NPs was converted to the "closed" form (CF), and photosensitization was activated. The CF of DAE-TPE NPs exhibited sufficient photodynamic therapy effects upon HeLa cells.


Assuntos
Antineoplásicos/química , Etilenos/química , Nanopartículas/química , Fármacos Fotossensibilizantes/química , Estilbenos/química , Antineoplásicos/farmacologia , Etilenos/farmacologia , Transferência Ressonante de Energia de Fluorescência , Células HeLa , Humanos , Luz , Conformação Molecular , Fotoquimioterapia , Fármacos Fotossensibilizantes/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Tiofenos/química
4.
Chem Commun (Camb) ; 57(22): 2800-2803, 2021 Mar 16.
Artigo em Inglês | MEDLINE | ID: mdl-33599643

RESUMO

Based on the thiolysis of dinitrophenyl ethers, a nucleus-targeted fluorescent probe, AQD, with bisalkylaminoanthraquinone as the fluorophore, was prepared for the near-infrared mapping of thiophenol in live cells, zebrafish, and mice.


Assuntos
Antraquinonas/química , Corantes Fluorescentes/química , Fenóis/análise , Compostos de Sulfidrila/análise , Animais , Camundongos , Espectrometria de Fluorescência , Poluentes Químicos da Água/análise , Peixe-Zebra
5.
J Control Release ; 324: 104-123, 2020 08 10.
Artigo em Inglês | MEDLINE | ID: mdl-32423873

RESUMO

Photocontrolled therapeutic release holds great promise due to its versatile manipulability, superb spatiotemporal precision and minimal tissue invasiveness in biomedical purposes. However, most of light-responsive platforms thus far have relied on UV or visible light which substantially limit the potential applicability in living animals. In recent decades, near-infrared (NIR) light-mediated theranostic upconversion nanocomposites (UCNCs) that integrate conventional UV/Vis-sensitive materials and classic lanthanide-doped upconversion nanoparticles (UCNPs) have significantly promoted the development of deep-tissue photoreleasable therapeutics in vivo. Herein, we seek to review current NIR upconversion triggered photorelease techniques and their diverse applications in the biological regulation, as well as diseases therapy. In addition, the future perspectives and challenges for advancing UCNCs based NIR photoreleasable nanotherapeutics into clinical translations are proposed.


Assuntos
Nanocompostos , Nanopartículas , Fotoquimioterapia , Animais
7.
Chem Commun (Camb) ; 55(44): 6301-6304, 2019 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-31089585

RESUMO

Based on the excimer-monomer conversion of a pyrene-flavone hybrid, a ratiometric CO photoreleaser, PFN, was constructed for simultaneous H2S quantification and CO release in inflammatory cells.


Assuntos
Monóxido de Carbono/metabolismo , Sulfeto de Hidrogênio/química , Processos Fotoquímicos , Fluorescência , Inflamação/metabolismo , Inflamação/patologia , Espectroscopia de Ressonância Magnética , Espectrometria de Massas
8.
Anal Chem ; 91(10): 6872-6879, 2019 05 21.
Artigo em Inglês | MEDLINE | ID: mdl-31001973

RESUMO

Peroxynitrite (ONOO-) is attracting increasing attention due to its involvement in multiple facets of pathophysiological processes. However, ONOO- bioimaging is still challenging due to (1) the lack of highly specific reaction triggers, (2) the tedious and low-yielding synthesis of current sophisticated probes, and (3) the lack of availability of a versatile chemical strategy. To address these challenges, on the basis of amine formylation/deformylation chemistry, we have developed a novel strategy for ONOO- bioimaging. As proof of principle, we designed, synthesized, and evaluated four novel fluorescent probes equipped with the formamide functionality. Although they feature distinctly different fluorophore classes, all probes can be synthesized in one step in high yields and exhibit particularly specific, highly sensitive, and rapid responses to ONOO-. The bioimaging capability is well demonstrated by successfully visualizing ONOO- fluctuation in live cells and major organs of mice suffering from paraquat poisoning. The proposed strategy has proved to be a facile, versatile, and highly efficient methodology for ONOO- visualization, which will greatly facilitate ONOO- biochemistry and pathophysiology.


Assuntos
Corantes Fluorescentes/química , Formamidas/química , Ácido Peroxinitroso/análise , Animais , Linhagem Celular Tumoral , Corantes Fluorescentes/síntese química , Formamidas/síntese química , Camundongos , Microscopia Confocal/métodos , Microscopia de Fluorescência/métodos , Paraquat/envenenamento , Ácido Peroxinitroso/química , Ácido Peroxinitroso/metabolismo , Envenenamento/metabolismo , Estudo de Prova de Conceito
9.
Anal Chem ; 91(9): 6097-6102, 2019 05 07.
Artigo em Inglês | MEDLINE | ID: mdl-30966737

RESUMO

A variety of fluorophores have been designed and created to fabricate organic fluorescent probes. Among these fluorophores, benzopyran-coumarin (BC) based fluorescent platform has attracted increasing attention as it shows multiple appropriate fluorescent and imaging capacities. Nevertheless, the analytical potential of BC is still urgently needed to be further excavated as its detection performance is hindered by the inherent drawbacks of current BC skeleton, that is, limited number of reactive sites. As such, in this work, by simply introducing electron-withdrawing (EW) substituent groups, we reconstructed BC skeleton to afford two fluorescent probes, BCB (-Br substitued) and BCN (-NO2 substitued), both of which featured two highly reactive sites. These two probes were capable of detecting peroxynitrite (ONOO-) and biothiols (hydrogen sulfide, glutathione, cysteine, and homocysteine) through naked eye and UV-vis absorption analysis in buffer solution. In addition, BCB was able to specifically sense biothiols with fluorescent analysis while BCN, with - NO2 instead of -Br, displayed more prominent fluorescent specificity toward ONOO-. This work provided a new strategy for the reactivity regulation of fluorophore through EW group introduction, as well as an alternative approach and method for the construction of fluorescent probes for other important biological species.


Assuntos
Benzopiranos/química , Cumarínicos/química , Elétrons , Corantes Fluorescentes/química , Ácido Peroxinitroso/análise , Compostos de Sulfidrila/análise , Animais , Corantes Fluorescentes/síntese química , Células Hep G2 , Humanos , Camundongos , Camundongos Endogâmicos , Estrutura Molecular , Imagem Óptica , Células PC12 , Ratos
10.
Chem Commun (Camb) ; 54(84): 11965-11968, 2018 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-30289138

RESUMO

Utilizing the oxidation/elimination tandem reaction of the α-phenylseleno carbonyl moiety, a two-photon fluorescent probe for ratiometric visualization of hypochlorous acid was developed. Its superior sensing performance and practical applications were well demonstrated.

11.
Anal Chem ; 90(19): 11629-11635, 2018 10 02.
Artigo em Inglês | MEDLINE | ID: mdl-30196694

RESUMO

Anthracyclines rank among the most efficacious anticancer medications. However, their clinical utility and oncologic efficacy are severely compromised by the cardiotoxicity risk facing the early-diagnosis difficulty and their unclear molecular mechanism. Herein, a two-photon-excitable and near-infrared-emissive fluorescent probe, TPNIR-FP, was fabricated and endowed with extraordinary specificity and sensitivity and a rapid response toward peroxynitrite (ONOO-), as well as mitochondria-targeting ability. With the aid of TPNIR-FP, we demonstrate that mitochondrial ONOO- is upregulated in the early stage and contributes to the onset and progression of anthracycline cardiotoxicity in cardiomyocyte and mouse models; therefore, it represents an early biomarker to predict subclinical cardiotoxicity induced by drug challenge. Furthermore, TPNIR-FP is proved to be a robust imaging tool to provide critical insights into drug-induced cardiotoxicity and other ONOO--related pathophysiological processes.


Assuntos
Antraciclinas/toxicidade , Corantes Fluorescentes/química , Mitocôndrias/química , Ácido Peroxinitroso/química , Espectroscopia de Luz Próxima ao Infravermelho/métodos , Animais , Antraciclinas/química , Corantes Fluorescentes/síntese química , Camundongos , Microscopia de Fluorescência por Excitação Multifotônica , Mitocôndrias/metabolismo , Modelos Animais , Miócitos Cardíacos/citologia , Miócitos Cardíacos/efeitos dos fármacos , Miócitos Cardíacos/metabolismo
12.
Angew Chem Int Ed Engl ; 57(38): 12415-12419, 2018 09 17.
Artigo em Inglês | MEDLINE | ID: mdl-30047607

RESUMO

Carbon monoxide (CO) is proposed as an active pharmaceutical agent with promising pharmaceutical prospects, as it has been involved in multifaceted modulation of diverse physiological and pathological processes. However, questions remain for therapeutic application of inhaled CO attributed to the inherent great affinity between CO and hemoglobin. Therefore, a robust platform with the function of CO transport and controllable release, depending on the local status of an organism, is of prominent significance for effectively avoiding the side effects of CO inhalation and optimizing the biological regulation function of CO. Utilizing the oxidative stress biomarker H2 O2 as a trigger and combining with photo-control, a two-photon H2 O2 -activated CO photoreleaser, FB, featuring highly sensitive and specific H2 O2 sensing and photocontrollable CO release, was developed and the vasodilation effect of CO against angiotensin II was demonstrated.


Assuntos
Monóxido de Carbono/metabolismo , Peróxido de Hidrogênio/química , Acetilcisteína/farmacologia , Angiotensina II/farmacologia , Animais , Boratos/química , Monóxido de Carbono/química , Flavonoides/química , Corantes Fluorescentes/química , Lasers , Músculo Liso Vascular/citologia , Músculo Liso Vascular/efeitos dos fármacos , Músculo Liso Vascular/metabolismo , Fotólise , Fótons , Espectrometria de Fluorescência , Peixe-Zebra/metabolismo
13.
Anal Chem ; 90(12): 7510-7516, 2018 06 19.
Artigo em Inglês | MEDLINE | ID: mdl-29781282

RESUMO

Drug-induced liver injury (DILI) has aroused wide concern. Finding new markers or indicators as well as detoxification molecules for DILI is of great significance and good application prospect, which can help develop effective preclinical screening methodology and corresponding treatment protocols. Herein, in this article, DILI caused by antidepressant drugs of duloxetine and fluoxetine and its remission were evaluated by a two-photon fluorescent probe, RPC-1, through discriminating and imaging HClO and H2S simultaneously. By being applied both in vitro and in vivo, RPC-1 revealed slight up-regulation of HClO and negligible liver damage after administration of either of the two drugs. In contrast, an apparent up-regulation of HClO and obvious liver damage was observed after combined administration of the drugs. Meanwhile, the pretreatment of N-acetyl cysteine (NAC) resulted in the increasing of endogenous H2S level, which contributed to the remission of DILI. The histological analysis and serological test both gave good consistency with the imaging results. These findings demonstrate that HClO may be an appropriate indicator of DILI, and H2S plays an important role in the antidotal effect of NAC. We envision that RPC-1 can be used as a powerful tool to predict clinical DILI and study the effect of antidote, as well as explore the molecular mechanisms involved.


Assuntos
Antidepressivos/efeitos adversos , Doença Hepática Induzida por Substâncias e Drogas/diagnóstico por imagem , Corantes Fluorescentes/química , Sulfeto de Hidrogênio/análise , Ácido Hipocloroso/análise , Imagem Óptica , Prótons , Doença Hepática Induzida por Substâncias e Drogas/patologia , Cloridrato de Duloxetina/efeitos adversos , Fluoxetina/efeitos adversos , Humanos , Estrutura Molecular
14.
Anal Chem ; 90(3): 1934-1940, 2018 02 06.
Artigo em Inglês | MEDLINE | ID: mdl-29293308

RESUMO

Magnetic resonance imaging (MRI) is a powerful diagnostic technique that can penetrate deep into tissue providing excellent spatial resolution without the need for ionizing radiation or harmful radionuclides. However, diagnosing bacterial infections in vivo with clinical MRI is severely hampered by the lack of contrast agents with high relaxivity, targeting capabilities, and bacterial penetration and specificity. Here, we report the development of the first gadolinium (Gd)-based bacteria-specific targeting MRI contrast agent, probe 1, by conjugating neomycin, an aminoglycoside antibiotic, with Dotarem (Gd-DOTA, an FDA approved T1-weighted MRI contrast agent). The T1 relaxivity of probe 1 was found to be comparable to that of Gd-DOTA; additionally, probe 1-treated bacteria generated a significantly brighter T1-weighted MR signal than Gd-DOTA-treated bacteria. More importantly, in vitro cellular studies and preliminary in vivo MRI demonstrated probe 1 exhibits the ability to efficiently target bacteria over macrophage-like cells, indicating its great potential for high-resolution imaging of bacterial infections in vivo.


Assuntos
Antibacterianos/química , Infecções Bacterianas/diagnóstico por imagem , Meios de Contraste/química , Compostos Heterocíclicos/química , Imageamento por Ressonância Magnética/métodos , Neomicina/análogos & derivados , Compostos Organometálicos/química , Animais , Antibacterianos/síntese química , Meios de Contraste/síntese química , Escherichia coli/isolamento & purificação , Infecções por Escherichia coli/diagnóstico por imagem , Compostos Heterocíclicos/síntese química , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Neomicina/síntese química , Compostos Organometálicos/síntese química , Células RAW 264.7 , Infecções Estafilocócicas/diagnóstico por imagem , Staphylococcus aureus/isolamento & purificação
16.
Chem Commun (Camb) ; 53(87): 11941-11944, 2017 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-29051930

RESUMO

We report for the first time the development of a two-photon excitable NO photoreleaser, CNNO, for ratiometric imaging and tracking of NO release in live cells. CNNO exhibits the merits of spatiotemporal control in both the site-specific NO release in the selected cell culture region and the controllable vasodilation of mouse aorta ex vivo.


Assuntos
Preparações de Ação Retardada/química , Corantes Fluorescentes/química , Gasotransmissores/administração & dosagem , Óxido Nítrico/administração & dosagem , Fótons , Animais , Cumarínicos/química , Liberação Controlada de Fármacos , Gasotransmissores/química , Células HeLa , Humanos , Luz , Camundongos , Naftalimidas/química , Óxido Nítrico/química
17.
Chem Sci ; 8(5): 4006-4011, 2017 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-28580117

RESUMO

Drug-induced injury has attracted increasing attention in public health issues. Among them, hepatotoxicity has been regarded as the leading clinical problem caused by drug toxicity. However, owing to the complexity of the involved pathophysiological mechanisms and the lack of noninvasive, straightforward, and real-time tools, drug-induced hepatotoxicity has rarely been predicted satisfactorily. In this paper, by utilizing the reactive species peroxynitrite (ONOO-) as a biomarker, we present a two-photon fluorescent probe, TP-KA, holding rapid response, high specificity and sensitivity towards ONOO-, to investigate drug (acetaminophen and tolcapone)-related liver injury and the remediate effect of N-acetyl cysteine (NAC). With the support of TP-KA, we obtained direct and visual evidence of the upregulation of ONOO- during drug challenge both in live cells and mice, which was accompanied by liver tissue injury and tyrosine nitration. These findings demonstrate that ONOO- is a good and appropriate biomarker of hepatotoxicity, and nitrosative stress may be necessary for acetaminophen and tolcapone to exert their toxicity. Moreover, TP-KA can be employed as a powerful tool to pre-detect drug-induced organism injury and study the effect of antidotes.

18.
Chem Commun (Camb) ; 53(48): 6520-6523, 2017 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-28573306

RESUMO

Lyso-TPFP presents lysosomal targetability and an acidic pH-activatable response toward formaldehyde. Thus, it exclusively visualizes lysosomal formaldehyde and is immune against it in neutral cytosol and other organelles. In addition, two-photon fluorescence imaging endows Lyso-TPFP with the capability of in situ tracking formaldehyde in live cells and animals.


Assuntos
Corantes Fluorescentes/química , Corantes Fluorescentes/farmacocinética , Formaldeído/análise , Lisossomos/metabolismo , Imagem Óptica , Fótons , Animais , Sobrevivência Celular , Fluorescência , Corantes Fluorescentes/síntese química , Células HeLa , Células Hep G2 , Humanos , Concentração de Íons de Hidrogênio , Camundongos
19.
Anal Chem ; 89(13): 7210-7215, 2017 07 05.
Artigo em Inglês | MEDLINE | ID: mdl-28573846

RESUMO

Biological sensors with simultaneous turn-on signals of fluorescence (FL) and chemiluminescence (CL) triggered by one single species are supposed to integrate spatiotemporally resolved FL imaging with dynamic CL sensing into one luminescent assay. Efficiently increased accuracy can be expected based on complementary information simultaneously obtained from two independent modes, which is crucial in disease detection and diagnosis. However, very few examples can be found to date because of the key challenges in the rational design of sensing structures. Herein, aggregation-induced emission (AIE) was employed to develop a novel organic platform TPE-CLA with simultaneous turn-on FL/CL signals specifically modulated by O2•- in cells, which can be attributed to the activation of AIE resulted from the decreasing solubility after recognition. Using imidazopyrazinone (CLA) as the reactive motif and tetraphenylethene (TPE) as FL/CL enhancing skeleton, TPE-CLA is sensitive enough to image native O2•- in Raw264.7 cells and lipopolysaccharide stimulated O2•- in mice. Endogenous O2•- in HL-7702 cells induced by acetaminophen (APAP) was uninterruptedly monitored for 7200 s with CL and the results were further confirmed by FL imaging. Accordingly, TPE-CLA turns out to be a reliable candidate for real-time and continuous monitoring of endogenous O2•- in live cells. The strategy utilizing AIE to accomplish the FL/CL dual detection is expected to extend the application of AIE as reaction-activated biosensors.

20.
Anal Chem ; 89(5): 3015-3020, 2017 03 07.
Artigo em Inglês | MEDLINE | ID: mdl-28192974

RESUMO

We present a feasible paradigm of developing original fluorescent probes for target biomolecules via combinatorial chemistry. In this developmental program, pyrimidine moieties were investigated and optimized as unique recognition units for thiols for the first time through a parallel synthesis in combination with a rapid screening process. This time-efficient and cost-saving process effectively facilitated the developmental progress and provided detailed structure-reactivity relationships. As a result, Res-Biot and Flu-Pht were identified as optimal fluorescent probes for biothiol and thiophenol, respectively. Their favorable characteristics and superior applicability have been well demonstrated in both chemical and biological contexts. In particular, Res-Biot enables the direct visualization of biothiol fluctuations during oxidative stress and cell apoptosis, indicating its suitability in elucidation of a specific pathophysiological process in both living cells and living animals. Meanwhile, Flu-Pht is competent to visualize thiophenols without the interference from endogenous biothiols in living cells.


Assuntos
Corantes Fluorescentes/química , Fenóis/análise , Pirimidinas/química , Compostos de Sulfidrila/análise , Animais , Cisteína/análise , Glutationa/análise , Células HeLa , Células Hep G2 , Homocisteína/análise , Humanos , Camundongos , Microscopia de Fluorescência , Imagem Óptica , Fenóis/química , Compostos de Sulfidrila/química
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