Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 22
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
Chem Sci ; 12(29): 10054-10062, 2021 Jul 28.
Artigo em Inglês | MEDLINE | ID: mdl-34377399

RESUMO

Precise detection of cellular senescence may allow its role in biological systems to be evaluated more effectively, while supporting studies of therapeutic candidates designed to evade its detrimental effect on physical function. We report here studies of α-l-fucosidase (α-fuc) as a biomarker for cellular senescence and the development of an α-fuc-responsive aggregation induced emission (AIE) probe, termed QM-NHαfuc designed to complement more conventional probes based on ß-galactosidase (ß-gal). Using QM-NHαfuc, the onset of replicative-, reactive oxygen species (ROS)-, ultraviolet A (UVA)-, and drug-induced senescence could be probed effectively. QM-NHαfuc also proved capable of identifying senescent cells lacking ß-gal expression. The non-invasive real-time senescence tracking provided by QM-NHαfuc was validated in an in vivo senescence model. The results presented in this study lead us to suggest that the QM-NHαfuc could emerge as a useful tool for investigating senescence processes in biological systems.

2.
Cell Rep ; 36(6): 109516, 2021 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-34380043

RESUMO

Although tumor-infiltrating lymphocytes (TILs) maintain their ability to proliferate, persist, and eradicate tumors, they are frequently dysfunctional in situ. By performing both whole-genome CRISPR and metabolic inhibitor screens, we identify that nicotinamide phosphoribosyltransferase (NAMPT) is required for T cell activation. NAMPT is low in TILs, and its expression is controlled by the transcriptional factor Tubby (TUB), whose activity depends on the T cell receptor-phospholipase C gamma (TCR-PLCγ) signaling axis. The intracellular level of NAD+, whose synthesis is dependent on the NAMPT-mediated salvage pathway, is also decreased in TILs. Liquid chromatography-mass spectrometry (LC-MS) and isotopic labeling studies confirm that NAD+ depletion led to suppressed glycolysis, disrupted mitochondrial function, and dampened ATP synthesis. Excitingly, both adoptive CAR-T and anti-PD1 immune checkpoint blockade mouse models demonstrate that NAD+ supplementation enhanced the tumor-killing efficacy of T cells. Collectively, this study reveals that an impaired TCR-TUB-NAMPT-NAD+ axis leads to T cell dysfunction in the tumor microenvironment, and an over-the-counter nutrient supplement of NAD+ could boost T-cell-based immunotherapy.

3.
Angew Chem Int Ed Engl ; 60(46): 24549-24557, 2021 11 08.
Artigo em Inglês | MEDLINE | ID: mdl-34425040

RESUMO

The occurrence and transmission of chirality is a fascinating characteristic of nature. However, the intermolecular transmission efficiency of circularly polarized luminescence (CPL) remains challenging due to poor through-space energy transfer. We report a unique CPL transmission from inducing the achiral acceptor to emit CPL within a specific liquid crystal (LC)-based intermolecular system through a circularly polarized fluorescence resonance energy transfer (C-FRET), wherein the luminescent cholesteric LC is employed as the chirality donor, and rationally designed achiral long-wavelength aggregation-induced emission (AIE) fluorophore acts as the well-assembled acceptor. In contrast to photon-release-and-absorption, the chirality transmission channel of C-FRET is highly dependent upon the energy resonance in the highly intrinsic chiral assembly of cholesteric LC, as verified by deliberately separating the achiral acceptor from the chiral donor to keep it far beyond the resonance distance. This C-FRET mode provides a de novo strategy concept for high-level information processing for applications such as high-density data storage, combinatorial logic calculation, and multilevel data encryption and decryption.

4.
Chem Sci ; 12(29): 9885-9894, 2021 Jul 28.
Artigo em Inglês | MEDLINE | ID: mdl-34349961

RESUMO

ß-Galactosidase (ß-gal), a typical hydrolytic enzyme, is a vital biomarker for cell senescence and primary ovarian cancers. Developing precise and rapid methods to monitor ß-gal activity is crucial for early cancer diagnoses and biological research. Over the past decade, activatable optical probes have become a powerful tool for real-time tracking and in vivo visualization with high sensitivity and specificity. In this review, we summarize the latest advances in the design of ß-gal-activatable probes via spectral characteristics and responsiveness regulation for biological applications, and particularly focus on the molecular design strategy from turn-on mode to ratiometric mode, from aggregation-caused quenching (ACQ) probes to aggregation-induced emission (AIE)-active probes, from near-infrared-I (NIR-I) imaging to NIR-II imaging, and from one-mode to dual-mode of chemo-fluoro-luminescence sensing ß-gal activity.

5.
Nat Commun ; 12(1): 3869, 2021 06 23.
Artigo em Inglês | MEDLINE | ID: mdl-34162875

RESUMO

Intramolecular charge transfer (ICT) is a fundamental mechanism that enables the development of numerous fluorophores and probes for bioimaging and sensing. However, the electron-withdrawing targets (EWTs)-induced fluorescence quenching is a long-standing and unsolved issue in ICT fluorophores, and significantly limits the widespread applicability. Here we report a simple and generalizable structural-modification for completely overturning the intramolecular rotation driving energy, and thus fully reversing the ICT fluorophores' quenching mode into light-up mode. Specifically, the insertion of an indazole unit into ICT scaffold can fully amplify the intramolecular rotation in donor-indazole-π-acceptor fluorophores (fluorescence OFF), whereas efficiently suppressing the rotation in their EWT-substituted system (fluorescence ON). This molecular strategy is generalizable, yielding a palette of chromophores with fluorescence umpolung that spans visible and near-infrared range. This strategy expands the bio-analytical toolboxes and allows exploiting ICT fluorophores for light-up sensing of EWTs including N-acetyltransferases and nerve agents.


Assuntos
Acetiltransferases/química , Fluorescência , Corantes Fluorescentes/química , Agentes Neurotóxicos/química , Acetiltransferases/metabolismo , Animais , Elétrons , Feminino , Células HeLa , Células Hep G2 , Humanos , Indazóis/química , Indazóis/metabolismo , Camundongos Endogâmicos BALB C , Camundongos Nus , Estrutura Molecular , Agentes Neurotóxicos/metabolismo , Teoria Quântica , Espectrometria de Fluorescência
6.
Nat Commun ; 12(1): 2622, 2021 05 11.
Artigo em Inglês | MEDLINE | ID: mdl-33976180

RESUMO

Obesity is caused by an imbalance between food intake and energy expenditure (EE). Here we identify a conserved pathway that links signalling through peripheral Y1 receptors (Y1R) to the control of EE. Selective antagonism of peripheral Y1R, via the non-brain penetrable antagonist BIBO3304, leads to a significant reduction in body weight gain due to enhanced EE thereby reducing fat mass. Specifically thermogenesis in brown adipose tissue (BAT) due to elevated UCP1 is enhanced accompanied by extensive browning of white adipose tissue both in mice and humans. Importantly, selective ablation of Y1R from adipocytes protects against diet-induced obesity. Furthermore, peripheral specific Y1R antagonism also improves glucose homeostasis mainly driven by dynamic changes in Akt activity in BAT. Together, these data suggest that selective peripheral only Y1R antagonism via BIBO3304, or a functional analogue, could be developed as a safer and more effective treatment option to mitigate diet-induced obesity.


Assuntos
Arginina/análogos & derivados , Obesidade/prevenção & controle , Receptores de Neuropeptídeo Y/antagonistas & inibidores , Termogênese/efeitos dos fármacos , Adipócitos/efeitos dos fármacos , Adipócitos/metabolismo , Tecido Adiposo Marrom/citologia , Tecido Adiposo Marrom/efeitos dos fármacos , Tecido Adiposo Marrom/metabolismo , Adulto , Animais , Arginina/farmacologia , Arginina/uso terapêutico , Biópsia , Células Cultivadas , Dieta Hiperlipídica/efeitos adversos , Modelos Animais de Doenças , Metabolismo Energético/efeitos dos fármacos , Feminino , Humanos , Masculino , Camundongos , Pessoa de Meia-Idade , Obesidade/etiologia , Obesidade/metabolismo , Cultura Primária de Células , Receptores de Neuropeptídeo Y/metabolismo
7.
Angew Chem Int Ed Engl ; 60(17): 9553-9561, 2021 04 19.
Artigo em Inglês | MEDLINE | ID: mdl-33569863

RESUMO

Photocaging holds promise for the precise manipulation of biological events in space and time. However, current near-infrared (NIR) photocages are oxygen-dependent for their photolysis and lack of timely feedback regulation, which has proven to be the major bottleneck for targeted therapy. Herein, we present a hypoxia-dependent photo-activation mechanism of dialkylamine-substituted cyanine (Cy-NH) accompanied by emissive fragments generation, which was validated with retrosynthesis and spectral analysis. For the first time, we have realized the orthogonal manipulation of this hypoxia-dependent photocaging and dual-modal optical signals in living cells and tumor-bearing mice, making a breakthrough in the direct spatiotemporal control and in vivo feedback regulation. This unique photoactivation mechanism overcomes the limitation of hypoxia, which allows site-specific remote control for targeted therapy, and expands the photo-trigger toolbox for on-demand drug release, especially in a physiological context with dual-mode optical imaging under hypoxia.


Assuntos
Carbocianinas/química , Hipóxia , Neoplasias Experimentais/diagnóstico por imagem , Técnicas Fotoacústicas , Células A549 , Animais , Liberação Controlada de Fármacos , Células Hep G2 , Humanos , Raios Infravermelhos , Camundongos , Estrutura Molecular , Imagem Óptica , Fotólise
8.
Angew Chem Int Ed Engl ; 59(47): 21143-21150, 2020 11 16.
Artigo em Inglês | MEDLINE | ID: mdl-32729980

RESUMO

Unpredictable in vivo therapeutic feedback of hydroxyl radical (. OH) efficiency is the major bottleneck of chemodynamic therapy. Herein, we describe novel Fenton-based nanotheranostics NQ-Cy@Fe&GOD for spatio-temporally reporting intratumor . OH-mediated treatment, which innovatively unites dual-channel near-infrared (NIR) fluorescence and magnetic resonance imaging (MRI) signals. Specifically, MRI signal traces the dose distribution of Fenton-based iron oxide nanoparticles (IONPs) with high-spatial resolution, meanwhile timely fluorescence signal quantifies . OH-mediated therapeutic response with high spatio-temporal resolution. NQ-Cy@Fe&GOD can successfully monitor the intracellular release of IONPs and . OH-induced NQO1 enzyme in living cells and tumor-bearing mice, which makes a breakthrough in conquering the inherent unpredictable obstacles on spatio-temporally reporting chemodynamic therapy, so as to manipulate dose-dependent therapeutic process.


Assuntos
Antineoplásicos/farmacologia , Peróxido de Hidrogênio/farmacologia , Radical Hidroxila/farmacologia , Ferro/farmacologia , Nanopartículas Magnéticas de Óxido de Ferro/química , Imageamento por Ressonância Magnética , Imagem Óptica , Células A549 , Animais , Antineoplásicos/síntese química , Antineoplásicos/química , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Dicumarol/farmacologia , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Peróxido de Hidrogênio/síntese química , Peróxido de Hidrogênio/química , Radical Hidroxila/química , Raios Infravermelhos , Ferro/química , Camundongos , Camundongos Nus , Estrutura Molecular , NAD(P)H Desidrogenase (Quinona)/antagonistas & inibidores , NAD(P)H Desidrogenase (Quinona)/metabolismo , Neoplasias Experimentais/diagnóstico por imagem , Neoplasias Experimentais/tratamento farmacológico , Neoplasias Experimentais/metabolismo
9.
Nat Commun ; 11(1): 793, 2020 02 07.
Artigo em Inglês | MEDLINE | ID: mdl-32034152

RESUMO

Fluorescence-based technologies have revolutionized in vivo monitoring of biomolecules. However, significant technical hurdles in both probe chemistry and complex cellular environments have limited the accuracy of quantifying these biomolecules. Herein, we report a generalizable engineering strategy for dual-emission anti-Kasha-active fluorophores, which combine an integrated fluorescein with chromene (IFC) building block with donor-π-acceptor structural modification. These fluorophores exhibit an invariant near-infrared Kasha emission from the S1 state, while their anti-Kasha emission from the S2 state at around 520 nm can be finely regulated via a spirolactone open/closed switch. We introduce bio-recognition moieties to IFC structures, and demonstrate ratiometric quantification of cysteine and glutathione in living cells and animals, using the ratio (S2/S1) with the S1 emission as a reliable internal reference signal. This de novo strategy of tuning anti-Kasha-active properties expands the in vivo ratiometric quantification toolbox for highly accurate analysis in both basic life science research and clinical applications.


Assuntos
Bioquímica/métodos , Corantes Fluorescentes/química , Imagem Molecular/métodos , Células A549 , Animais , Benzopiranos/química , Cisteína/análise , Feminino , Fluoresceína/química , Corantes Fluorescentes/síntese química , Corantes Fluorescentes/metabolismo , Glutationa/análise , Células Hep G2 , Humanos , Camundongos Endogâmicos BALB C , Estrutura Molecular , Neoplasias Experimentais/diagnóstico por imagem , Piranos/química , Espectroscopia de Luz Próxima ao Infravermelho/métodos , Espironolactona/química
10.
Angew Chem Int Ed Engl ; 59(23): 9059-9066, 2020 06 02.
Artigo em Inglês | MEDLINE | ID: mdl-31984609

RESUMO

Chemiluminescence (CL)-based technologies have revolutionized in vivo monitoring of biomolecules. However, significant technical hurdles have limited the achievement of trigger-controlled, bright, and enriched CL signal. Herein, a dual-lock strategy uses sequence-dependent triggers for bright optical imaging with real-time fluorescent signal and ultra-sensitive CL signal. These probes can obtain an analyte-triggered accumulation of stable pre-chemiluminophore with aggregation-induced emission (AIE), and then the pre-chemiluminophore exhibits a rapid photooxidation process (1,2-dioxetane generation) by TICT-based free-radical addition, thereby achieving an enrichment and bright CL signal. The dual-lock strategy expands the in vivo toolbox for highly accurate analysis and has for the first time allowed access to accurately sense and trace biomolecules with high-resolution, dual-mode of chemo-fluoro-luminescence, and three-dimensional (3D) imaging in living animals.


Assuntos
Substâncias Luminescentes/química , Imagem Óptica/métodos , Animais , Linhagem Celular Tumoral , Transformação Celular Neoplásica , Imageamento Tridimensional , Cinética , Camundongos , Oxirredução , Processos Fotoquímicos , Fatores de Tempo
11.
Angew Chem Int Ed Engl ; 59(25): 9812-9825, 2020 06 15.
Artigo em Inglês | MEDLINE | ID: mdl-31725932

RESUMO

In vivo fluorescent monitoring of physiological processes with high-fidelity is essential in disease diagnosis and biological research, but faces extreme challenges due to aggregation-caused quenching (ACQ) and short-wavelength fluorescence. The development of high-performance and long-wavelength aggregation-induced emission (AIE) fluorophores is in high demand for precise optical bioimaging. The chromophore quinoline-malononitrile (QM) has recently emerged as a new class of AIE building block that possesses several notable features, such as red to near-infrared (NIR) emission, high brightness, marked photostability, and good biocompatibility. In this minireview, we summarize some recent advances of our established AIE building block of QM, focusing on the AIE mechanism, regulation of emission wavelength and morphology, the facile scale-up and fast preparation for AIE nanoparticles, as well as potential biomedical imaging applications.


Assuntos
Corantes Fluorescentes/síntese química , Nitrilas/química , Imagem Óptica/métodos , Quinolinas/química , Raios Infravermelhos
12.
Chem Sci ; 11(12): 3371-3377, 2020 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-34122845

RESUMO

Glucose oxidase (GOD)-based synergistic cancer therapy has aroused great research interest in the context of cancer treatment due to the inherent biocompatibility and biodegradability. However, this emerging therapeutic system still lacks a strategy to predict and regulate the in vivo biocatalytic behavior of GOD in real time to minimize the side effects on normal tissues. Herein, we developed a tumor-specific cascade nanotheranostic system (BNG) that combines GOD-catalyzed oxidative stress and dual-channel fluorescent sensing, significantly improving the synergistic therapeutic efficacy with real-time feedback information. The nanotheranostic system remains completely silent in the blood circulatory system and selectively releases GOD enzymes in the tumor site, with enhanced near-infrared (NIR) fluorescence at 825 nm. Subsequently, GOD catalyzes H2O2 production, triggering cascade reactions with NIR fluorescence at 650 nm as an optical output, along with GSH depletion, enabling synergistic cancer treatment. The designed nanotheranostic system, integrated with tumor-activated cascade reactions and triggering a dual-channel output at each step, represents an insightful paradigm for precise cooperative cancer therapy.

13.
Chem Commun (Camb) ; 55(82): 12308-12311, 2019 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-31556426

RESUMO

Herein, we developed a dual-channel and light-up near-infrared fluorescent probe for ratiometric sensing of ß-galactosidase (ß-gal) activity. The well-designed probe, which shows ratiometric optical response with a significant red-shift (from 575 nm to 730 nm), was successfully applied to detect endogenous ß-gal activity in SKOV-3 cells and tumor-bearing mice.


Assuntos
Corantes Fluorescentes/análise , Corantes Fluorescentes/química , beta-Galactosidase/análise , beta-Galactosidase/metabolismo , Animais , Linhagem Celular Tumoral , Células Hep G2 , Humanos , Raios Infravermelhos , Camundongos , Camundongos Nus , Estrutura Molecular , Neoplasias Experimentais/diagnóstico por imagem , Imagem Óptica
14.
Front Chem ; 7: 291, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31139612

RESUMO

High-fidelity tracking of specific enzyme activities is critical for the early diagnosis of diseases such as cancers. However, most of the available fluorescent probes are difficult to obtain in situ information because of tending to facile diffusion or inevitably suffering from aggregation-caused quenching (ACQ) effect. In this work, we developed an elaborated near-infrared (NIR) aggregation-induced emission (AIE)-active fluorescent probe, which is composed of a hydrophobic 2-(2-hydroxyphenyl) benzothiazole (HBT) moiety for extending into the NIR wavelength, and a hydrophilic ß-galactosidase (ß-gal) triggered unit for improving miscibility and guaranteeing its non-emission in aqueous media. This probe is virtually activated by ß-gal, and then specific enzymatic turnover would liberate hydrophobic AIE luminogen (AIEgen) QM-HBT-OH. Simultaneously, brightness NIR fluorescent nanoaggregates are in situ generated as a result of the AIE-active process, making on-site the detection of endogenous ß-gal activity in living cells. By virtue of the NIR AIE-active performance of enzyme-catalyzed nanoaggregates, QM-HBT-ßgal is capable of affording a localizable fluorescence signal and long-term tracking of endogenous ß-gal activity. All results demonstrate that the probe QM-HBT-ßgal has potential to be a powerful molecular tool to evaluate the biological activity of ß-gal, attaining high-fidelity information in preclinical applications.

15.
Chem Sci ; 10(2): 398-405, 2019 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-30746088

RESUMO

Development of fluorescent probes for on-site sensing and long-term tracking of specific biomarkers is particularly desirable for the early detection of diseases. However, available small-molecule probes tend to facilely diffuse across the cell membrane or remain at the activation site but always suffer from the aggregation-caused quenching (ACQ) effect. Here we report an enzyme-activatable aggregation-induced emission (AIE) probe QM-ßgal, which is composed of a hydrophilic ß-galactosidase (ß-gal)-triggered galactose moiety and a hydrophobic AIE-active fluorophore QM-OH. The probe is virtually non-emissive in aqueous media, but when activated by ß-gal, specific enzymatic turnover would liberate hydrophobic AIE luminogen (AIEgen) QM-OH, and then highly fluorescent nanoaggregates are in situ generated as a result of the AIE process, allowing for on-site sensing of endogenous ß-gal activity in living cells. Notably, taking advantage of the improved intracellular retention of nanoaggregates, we further exemplify QM-ßgal for long-term (∼12 h) visualization of ß-gal-overexpressing ovarian cancer cells with high fidelity, which is essential for biomedicine and diagnostics. Thus, this enzyme-activatable AIE probe not only is a potent tool for elucidating the roles of ß-gal in biological systems, but also offers an enzyme-regulated liberation strategy to exploit multifunctional probes for preclinical applications.

16.
J Am Chem Soc ; 141(7): 3171-3177, 2019 02 20.
Artigo em Inglês | MEDLINE | ID: mdl-30632737

RESUMO

High-fidelity mapping of amyloid-ß (Aß) plaques is critical for the early detection of Alzheimer's disease. However, in vivo probing of Aß plaques by commercially available thioflavin derivatives (ThT or ThS) has proven to be extremely limited, as evident by the restriction of enrichment quenching effect, low signal-to-noise ( S/ N) ratio, and poor blood-brain barrier (BBB) penetrability. Herein, we demonstrate a rational design strategy of near-infrared (NIR) aggregation-induced emission (AIE)-active probes for Aß plaques, through introducing a lipophilic π-conjugated thiophene-bridge for extension to NIR wavelength range with enhancement of BBB penetrability, and tuning the substituted position of the sulfonate group for guaranteeing specific hydrophilicity to maintain the fluorescence- off state before binding to Aß deposition. Probe QM-FN-SO3 has settled well the AIE dilemma between the lipophilic requirement for longer emission and aggregation behavior from water to protein fibrillogenesis, thus making a breakthrough in high-fidelity feedback on in vivo detection of Aß plaques with remarkable binding affinity, and serving as an efficient alternative to the commercial probe ThT or ThS.


Assuntos
Alcanossulfonatos/química , Corantes Fluorescentes/química , Placa Amiloide/diagnóstico por imagem , Quinolinas/química , Alcanossulfonatos/metabolismo , Doença de Alzheimer/diagnóstico por imagem , Doença de Alzheimer/patologia , Peptídeos beta-Amiloides/metabolismo , Precursor de Proteína beta-Amiloide/genética , Animais , Barreira Hematoencefálica/metabolismo , Encéfalo/patologia , Corantes Fluorescentes/metabolismo , Humanos , Masculino , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Imagem Óptica , Fragmentos de Peptídeos/metabolismo , Placa Amiloide/patologia , Presenilina-1/genética , Ligação Proteica , Quinolinas/metabolismo
17.
Environ Sci Technol ; 53(15): 8631-8639, 2019 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-30511839

RESUMO

The influence of solution chemistry on the adsorption of human serum albumin (HSA) proteins on graphene oxide (GO) was investigated through batch adsorption experiments and the use of a quartz crystal microbalance with dissipation (QCM-D). The conformation of HSA layers on GO was also examined with the QCM-D. Our results show that an increase in ionic strength under neutral pH conditions resulted in stronger binding between HSA and GO, as well as more compact HSA layers on GO, emphasizing the key role of electrostatic interactions in controlling HSA-GO interactions. Calcium ions also facilitated HSA adsorption likely through charge neutralization and bridging effect. At physiological ionic strength conditions (150 mM), maximum HSA adsorption was observed at the isoelectric point of HSA (4.7). Under acidic conditions, the adsorption of HSA on GO led to the formation of protein layers with a high degree of fluidity due to the extended conformation of HSA. Finally, the attachment of GO to a supported lipid bilayer that was composed of zwitterionic 1,2-dioleoyl-sn-glycero-3-phosphocholine, a model for cell membranes, was reduced in the presence of protein coronas. This reduction in GO attachment was influenced by the conformation of the protein coronas on GO.


Assuntos
Grafite , Coroa de Proteína , Adsorção , Humanos , Óxidos , Técnicas de Microbalança de Cristal de Quartzo , Albumina Sérica Humana , Propriedades de Superfície
18.
Adv Mater ; 31(3): e1805735, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30484912

RESUMO

The accuracy of traditional bischromophore-based ratiometric probes is always compromised by undesirable energy/charge transferring interactions between the internal reference moiety and the sensing chromophore. In this regard, ratiometric sensing with a monochromophore system is highly desirable. Herein, an unprecedented monochromophore-based ratiometric probe, which consists of a hydrophilic backbone poly(N-vinylpyrrolidone) (PVP) and single chromophore of platinum(II) tetraphenylporphyrin (Pt-TPP) is reported. Combination of the specific assembled clustering-triggered fluorescent emission (oxygen-insensitive) with the original Pt-TPP phosphorescence (oxygen-sensitive) enables successful construction of a monochromophore-based ratiometric nanosensor for directly tracing hypoxia in vivo, along with the preferable facilitation of enhanced permeation and retention effect and long excitation wavelength. The unique ratiometric signals enable the direct observation from normoxic to hypoxic environment in both living A549 cells and a tumor-bearing mice model, providing a significant paradigm of a monochromophore-based dual-emissive system with the specific assembled cluster emission. The work satisfactorily demonstrates a valuable strategy for designing monochromophore-based dual-emissive materials, and validates its utility for in vivo ratiometric biological sensing without the common energy/charge interference in bischromophore-based system.


Assuntos
Hipóxia/diagnóstico por imagem , Hipóxia/metabolismo , Imagem Óptica , Polivinil , Pirrolidinas , Animais , Linhagem Celular Tumoral , Humanos , Interações Hidrofóbicas e Hidrofílicas , Camundongos , Transplante de Neoplasias , Neoplasias/diagnóstico por imagem , Neoplasias/metabolismo , Compostos de Platina , Porfirinas
19.
Chem Commun (Camb) ; 54(87): 12393-12396, 2018 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-30328423

RESUMO

A curcuminoid difluoroboron-based tumor-targeting GGT-activatable fluorescent probe (Glu-DFB-biotin) is designed, which has remarkable characteristics of dual-channel and light-up near-infrared (NIR) fluorescence. Furthermore, Glu-DFB-biotin can differentiate hepatic cancer cells from normal cells and is successfully employed for real-time tracking of endogenous GGT activity in living cells.


Assuntos
Corantes Fluorescentes/química , gama-Glutamiltransferase/metabolismo , Diagnóstico Diferencial , Hepatócitos/enzimologia , Humanos , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/enzimologia , Espectrometria de Fluorescência , Espectroscopia de Luz Próxima ao Infravermelho
20.
Chem Sci ; 9(29): 6176-6182, 2018 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-30090304

RESUMO

The translation of biomarker sensing into programmable diagnostics or therapeutic applications in vivo is greatly challenging, especially for eliminating the 'false positive' signals from OR logic gates. Herein we present a sense-of-logic dual-channel nanoprobe, operating through a sequence-activated AND logic gate by responding ultra-sensitively to pH changes and being subsequently triggered with biothiol for the controllable release of anti-cancer drugs. Specifically, programmable drug release is conducted in a multistage tumor microenvironment (acidic endocytic organelles followed by abnormal glutathione-overexpressing cell cytosol), which is synchronous with dual-channel near-infrared (NIR) fluorescence output. This approach represents the merging of sensing and release, including logically enabled molecular design, biomarker sensing, and controllable drug release. Impressively, the sequential AND logic feature within an unprecedented framework provides feedback on the diversity and complexity of biological milieu, along with remarkably enhancing the tumor therapeutic efficiency via its precise targeting ability and programmable drug release.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...