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1.
Angew Chem Int Ed Engl ; : e202416963, 2024 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-39387351

RESUMO

Photodynamic therapy (PDT) is a clinically approved therapeutic modality that has shown great potential for cancer treatment. However, there exist two major problems hindering PDT applications: the nonspecific phototoxicity requiring patients to stay in dark post-PDT, and the limited photodynamic efficiency. Herein, we report a photo-triggered porphyrin polyelectrolyte nanoassembling (photo-triggered PPN) strategy, in which porphyrin photosensitizer and photoswitchable energy accepter are assembled into polyelectrolyte micelles by a combined force of charge interaction and metal-ligand coordination. The polyelectrolyte-based PPN exhibits good biocompatibility, and bestows a unique "confining isolated" inner microenvironment for fully overcoming the π-π stacking of porphyrins with significant photodynamic efficiency (123-fold enhancement). Due to the high Förster resonance energy transfer (FRET) (91.5%) between porphyrin and photoswitch in closed-form, we could use light as a specific trigger to modulate photoswitch between closed- and open-form, and manipulate the 1O2 generation in three stages: pre-PDT (quenching 1O2 generation), during PDT (activating 1O2 generation), and post-PDT (silencing 1O2 generation). This de novo strategy has for the first time realized remotely manipulating and boosting 1O2 generation in PDT, well resolving the critical and general challenges of limited photodynamic efficiency and side effects from nonspecific phototoxicity.

2.
Chem Sci ; 15(31): 12431-12441, 2024 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-39118631

RESUMO

Singlet oxygen (1O2), as a fundamental hallmark in photodynamic therapy (PDT), enables ground-breaking clinical treatment in ablating tumors and killing germs. However, accurate in vivo monitoring of 1O2 remains a significant challenge in probe design, with primary difficulties arising from inherent photo-induced side reactions with poor selectivity. Herein, we report a generalizable zwitterionic strategy for ultra-stable near-infrared (NIR) chemiluminescent probes that ensure a highly specific [2 + 2] cycloaddition between fragile electron-rich enolether units and 1O2 in both cellular and dynamic in vivo domains. Innovatively, zwitterionic chemiluminescence (CL) probes undergo a conversion into an inert ketone excited state with an extremely short lifetime through conical intersection (CI), thereby affording sufficient photostability and suppressing undesired photoreactions. Remarkably, compared with the well-known commercial 1O2 probe SOSG, the zwitterionic probe QMI exhibited an ultra-high signal-to-noise ratio (SNR, over 40-fold). Of particular significance is that the zwitterionic CL probes demonstrate excellent selectivity, high sensitivity, and outstanding photostability, thereby making a breakthrough in real-time tracking of the FDA-approved 5-ALA-mediated in vivo PDT process in living mice. This innovative zwitterionic strategy paves a new pathway for high-performance NIR chemiluminescent probes and high-fidelity feedback on 1O2 for future biological and medical applications.

3.
Acta Biomater ; 177: 37-49, 2024 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-38364928

RESUMO

Inflammatory bowel disease (IBD) is a gastrointestinal immune disease that requires clear diagnosis, timely treatment, and lifelong monitoring. The diagnosis and monitoring methods of IBD mainly include endoscopy, imaging examination, and laboratory examination, which are constantly developed to achieve early definite diagnosis and accurate monitoring. In recent years, with the development of nanotechnology, the diagnosis and monitoring methods of IBD have been remarkably enriched. Nanomaterials, characterized by their minuscule dimensions that can be tailored, along with their distinctive optical, magnetic, and biodistribution properties, have emerged as valuable contrast agents for imaging and targeted agents for endoscopy. Through both active and passive targeting mechanisms, nanoparticles accumulate at the site of inflammation, thereby enhancing IBD detection. This review comprehensively outlines the existing IBD detection techniques, expounds upon the utilization of nanoparticles in IBD detection and diagnosis, and offers insights into the future potential of in vitro diagnostics. STATEMENT OF SIGNIFICANCE: Due to their small size and unique physical and chemical properties, nanomaterials are widely used in the biological and medical fields. In the area of oncology and inflammatory disease, an increasing number of nanomaterials are being developed for diagnostics and drug delivery. Here, we focus on inflammatory bowel disease, an autoimmune inflammatory disease that requires early diagnosis and lifelong monitoring. Nanomaterials can be used as contrast agents to visualize areas of inflammation by actively or passively targeting them through the intestinal mucosal epithelium where gaps exist due to inflammation stimulation. In this article, we summarize the utilization of nanoparticles in inflammatory bowel disease detection and diagnosis, and offers insights into the future potential of in vitro diagnostics.


Assuntos
Meios de Contraste , Doenças Inflamatórias Intestinais , Humanos , Distribuição Tecidual , Doenças Inflamatórias Intestinais/diagnóstico , Doenças Inflamatórias Intestinais/tratamento farmacológico , Mucosa Intestinal , Inflamação
4.
Anal Chem ; 95(30): 11273-11279, 2023 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-37478050

RESUMO

Dopamine (DA) is an important neurotransmitter, which not only participates in the regulation of neural processes but also plays critical roles in tumor progression and immunity. However, direct identification of DA-containing exosomes, as well as quantification of DA in single vesicles, is still challenging. Here, we report a nanopipette-assisted method to detect single exosomes and their dopamine contents via amperometric measurement. The resistive-pulse current measured can simultaneously provide accurate information of vesicle translocation and DA contents in single exosomes. Accordingly, DA-containing exosomes secreted from HeLa and PC12 cells under different treatment modes successfully detected the DA encapsulation efficiency and the amount of exosome secretion that distinguish between cell types. Furthermore, a custom machine learning model was constructed to classify the exosome signals from different sources, with an accuracy of more than 99%. Our strategy offers a useful tool for investigating single exosomes and their DA contents, which facilitates the analysis of DA-containing exosomes derived from other untreated or stimulated cells and may open up a new insight to the research of DA biology.

5.
Angew Chem Int Ed Engl ; 62(13): e202218983, 2023 03 20.
Artigo em Inglês | MEDLINE | ID: mdl-36700414

RESUMO

Uniting photothermal therapy (PTT) with magnetic resonance imaging (MRI) holds great potential in nanotheranostics. However, the extensively utilized hydrophobicity-driven assembling strategy not only restricts the intramolecular motion-induced PTT, but also blocks the interactions between MR agents and water. Herein, we report an aggregation-induced emission luminogen (AIEgen)-mediated polyelectrolyte nanoassemblies (APN) strategy, which bestows a unique "soft" inner microenvironment with good water permeability. Femtosecond transient spectra verify that APN well activates intramolecular motion from the twisted intramolecular charge transfer process. This de novo APN strategy uniting synergistically three factors (rotational motion, local motion, and hydration number) brings out high MR relaxivity. For the first time, APN strategy has successfully modulated both intramolecular motion and magnetic relaxivity, achieving fluorescence lifetime imaging of tumor spheroids and spatio-temporal MRI-guided high-efficient PTT.


Assuntos
Corantes Fluorescentes , Imageamento por Ressonância Magnética , Polieletrólitos , Água
6.
JACS Au ; 2(1): 246-257, 2022 Jan 24.
Artigo em Inglês | MEDLINE | ID: mdl-35098241

RESUMO

Pancreatic ductal adenocarcinoma (PDAC), as one of the most malignant tumors with dense desmoplastic stroma, forms a specific matrix barrier to hinder effective diagnosis and therapy. To date, a paramount challenge is in the search for intelligent nanotheranostics for such hypopermeable tumors, especially in breaking the PDAC-specific physical barrier. The unpredictable in vivo behaviors of nanotheranostics, that is, real-time tracking where, when, and how they cross the physical barriers and are taken up by tumor cells, are the major bottleneck. Herein, we elaborately design sequence-activated nanotheranostic TCM-U11&Cy@P with dual-channel near-infrared fluorescence outputs for monitoring in vivo behaviors in a sequential fashion. This nanotheranostic with a programmable targeting capability effectively breaks through the PDAC barriers. Ultimately, the released aggregation-induced emission (AIE) particle TCM-U11 directly interacts with PDAC cells and penetrates into the deep tissue. Impressively, this fluorescent nanotheranostic intraoperatively can map human clinical PDAC specimens with high resolution. We believe that this unique sequence-activated fluorescent strategy expands the repertoire of nanotheranostics in the treatment of hypopermeable tumors.

7.
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.

8.
Cell Rep ; 36(6): 109516, 2021 08 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.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Linfócitos do Interstício Tumoral/imunologia , NAD/farmacologia , Neoplasias/imunologia , Neoplasias/patologia , Nicotinamida Fosforribosiltransferase/genética , Linfócitos T/imunologia , Transcrição Gênica , Transferência Adotiva , Animais , Morte Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Metabolismo Energético/efeitos dos fármacos , Humanos , Ativação Linfocitária/efeitos dos fármacos , Linfócitos do Interstício Tumoral/efeitos dos fármacos , Camundongos Endogâmicos NOD , Neoplasias/genética , Nicotinamida Fosforribosiltransferase/metabolismo , Linfócitos T/efeitos dos fármacos , Transcrição Gênica/efeitos dos fármacos
9.
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
10.
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
11.
ACS Appl Bio Mater ; 4(3): 2001-2008, 2021 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-35014325

RESUMO

Cysteine (Cys) is well-known to be an important biothiol and related to many diseases. However, the in situ trapping of endogenous Cys is still handicapped by a lack of straightforward methods combined with long-wavelength emission and high-performance response. In this work, we described the rational design strategy of cyanine-based near-infrared (NIR) probes for the rapid detection of mitochondrial Cys in living cells and mice. We focus on how to improve the response rate via regulating the electron density of the recognition units in probes. The obtained three probes all displayed remarkable fluorescence enhancement at 780 nm. From screening the obtained probes, it was found that the probe Cy-S-diOMe with electron-donating recognition unit displayed the fastest response rate, the lowest detection limit, and the highest signal-to-noise ratio. More importantly, Cy-S-diOMe was successfully applied to monitor Cys in tumor-bearing mice (within merely 5 min). This paradigm by modulation of the response rate in the cyanine dyes provides a promising methodology for the design of high-performance cyanine-based NIR probes.


Assuntos
Materiais Biocompatíveis/química , Cisteína/análise , Desenho de Fármacos , Corantes Fluorescentes/química , Animais , Materiais Biocompatíveis/síntese química , Corantes Fluorescentes/síntese química , Células HeLa , Humanos , Raios Infravermelhos , Teste de Materiais , Camundongos , Estrutura Molecular , Neoplasias Experimentais/química , Neoplasias Experimentais/diagnóstico por imagem , Tamanho da Partícula
12.
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
13.
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
14.
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
15.
ACS Appl Bio Mater ; 3(1): 45-52, 2020 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-35019425

RESUMO

Precise in vivo tracking of hydrogen peroxide is still challenging due to its dynamic complexity and intrinsic background interference. Herein, we describe a rational design strategy to construct asymmetric aza-boron-dipyrromethane derivative (BODIPY)-based ratiometric probes for in vivo tracking H2O2, which are composed of a near-infrared aza-BODIPY core, active targeting group, and H2O2-specific recognition unit. We take advantage of two terminal functionalized conjunctions in the bis-condensed aza-BODIPY by rationally introducing carbonyl group as an electron-deficiency linker for regulating intramolecular charge transfer-induced wavelength shift and by attaching hydrophilic polyethylene glycol-biotin segment as the active targeting moiety. The probe BP5-NB-OB features several striking characteristics: (i) ratiometric near infrared response in both absorption and emission spectra; (ii) active targeting ability (biotin receptor-mediated endocytosis) with excellent biocompatibility; and (iii) in vivo tracking of endogenous H2O2. It was demonstrated that the probe BP5-NB-OB was successfully utilized for tracking endogenous H2O2 in living cells and tumor-bearing mice, providing opportunities to insight into H2O2 related diseases for clinical application.

16.
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.

17.
Chem Sci ; 10(30): 7222-7227, 2019 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-31588290

RESUMO

The advance of cancer imaging requires innovations to establish novel fluorescent scaffolds that are excitable and emit in the near-infrared region with favorable Stokes shifts. Nevertheless, the lack of probes with these optimized optical properties presents a major bottleneck in targeted cancer imaging. By coupling of boron dipyrromethene platforms to enzymic substrates via a self-immolative benzyl thioether linker, we here report a strategy toward enzyme-activated fluorescent probes to satisfy these requirements. This strategy is applicable to generate various BODIPY-based probes across the NIR spectrum via introducing diverse electron-withdrawing substituents at the 3-position of the BODIPY core through a vinylene unit. As expected, such designed probes show advantages of two-channel ratiometric fluorescence and light-up NIR (I and II) emission with large Stokes shifts upon enzyme activation, enabling targeted cancer cell imaging and accurate tumor location by real-time monitoring of enzyme activities. This strategy is promising in engineering activatable molecular probes suitable for precision medicine.

18.
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
19.
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.

20.
Chem Sci ; 10(9): 2785-2790, 2019 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-30996998

RESUMO

Development of theranostic probes that can be used to identify tumors and direct the on-demand drug administration to cancers is ongoing but remains challenging. Herein, we report a theranostic platform composed of a H2S-activated imaging probe and a light-sensitive drug. The designed probe affords advantages of H2S-activated NIR emission light-up and efficient 1O2 generation, enabling the selective visualization of H2S-rich cancers and the subsequent imaging-directed on-demand light exposure to the detected cancers while leaving normal tissues untouched. Such controllable administration of photodynamic anticancer therapy maximizes the therapeutic efficiency and minimizes side effects. This work should facilitate significant advances toward precise diagnosis and treatment of cancer.

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