RESUMO
Highly efficient triplet photosensitizers (PSs) have attracted increasing attention in cancer photodynamic therapy where photo-induced reactive oxygen species (ROSs, such as singlet oxygen) are produced via singlet-triplet intersystem crossing (ISC) of the excited photosensitizer to kill cancer cells. However, most PSs exhibit the fatal defect of a generally less-than-1% efficiency of ISC and low yield of ROSs, and this defect strongly impedes their clinical application. In the current work, a new strategy to enhance the ISC and high phototherapy efficiency has been developed, based on the molecular design of a thio-pentamethine cyanine dye (TCy5) as a photosensitizer. The introduction of an electron-withdrawing group at the meso-position of TCy5 could dramatically reduce the singlet-triplet energy gap (ΔE st) value (from 0.63 eV to as low as 0.14 eV), speed up the ISC process (τ ISC = 1.7 ps), prolong the lifetime of the triplet state (τ T = 319 µs) and improve singlet oxygen (1O2) quantum yield to as high as 99%, a value much higher than those of most reported triplet PSs. Further in vitro and in vivo experiments have shown that TCy5-CHO, with its efficient 1O2 generation and good biocompatibility, causes an intense tumor ablation in mice. This provides a new strategy for designing ideal PSs for cancer photo-therapy.
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Cardiovascular disease (CVD) is the number one threat that seriously endangers human health. However, the mechanism of their occurrence is not completely clear. Increasing studies showed that mitochondrial dysfunction is closely related to CVD. Possible causes of mitochondrial dysfunction include oxidative stress, Ca2+ disorder, mitochondrial DNA mutations, and reduction of mitochondrial biosynthesis, all of which are closely related to the development of CVD. At present, traditional Chinese medicine (TCM) is widely used in the treatment of CVD. TCM has the therapeutic characteristics of multitargets and multipathways. Studies have shown that TCM can treat CVD by protecting mitochondrial function. Via systematic literature review, the results show that the specific mechanisms include antioxidant stress, regulation of calcium homeostasis, antiapoptosis, and regulation of mitochondrial biosynthesis. This article describes the relationship between mitochondrial dysfunction and CVD, summarizes the TCM commonly used for the treatment of CVD in recent years, and focuses on the regulatory effect of TCM on mitochondrial function.
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A turn-on fluorescent probe for the detection of Fe2+ is facilely synthesized via a nucleophile substitution reaction. The fluorescent probe, N-butyl-4-phenyltellanyl-1,8-naphthalimide (Naph-Te), shows excellent selectivity to Fe2+ in a mixed solution of acetonitrile and phosphate buffer under aerobic conditions. The coexistence of biological abundant metal ions such as Na+, K+, Ca2+ and Mg2+ has little effect on the fluorescence signal. This turn-on response is achieved via a redox-involved reaction triggered by Fe2+ at neutral pH and room temperature, which removes the heavy-atom effect of the tellurium atom on the naphthalimide fluorophore to afford a fluorescent product (N-butyl-4-hydroxyl-1,8-naphthalimide). The probe has excellent cell membrane permeability and is further applied successfully to monitor supplementary Fe2+ in live HL-7702 cells using a laser confocal fluorescence microscope.
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Selenium is a biologically important trace element and acts as an active center of glutathione peroxidase (GPx). GPx is the important antioxidant enzyme to protect organisms from oxidative damage via catalyzing the reaction between ROS and glutathione (GSH). Mimicking the oxidation-reduction cycles of the versatile selenium core in GPx, we can develop fluorescence probes to detect oxidation and reduction events in living systems. The cellular redox balance between hypochloric acid (HClO) and hydrogen sulfide (H2S) has broad implications in human health and diseases, such as Alzheimer's disease (AD). Therefore, to further investigate the roles of this redox balance and understand the pathogenesis of neurodegenerative diseases, it is necessary to detect the redox state between HClO and H2S in real time. We have developed a reversible fluorescence probe MPhSe-BOD for imaging of the redox cycle between HClO and H2S based on oxidation and reduction of selenide in living cells.
Assuntos
Ácidos/química , Corantes Fluorescentes/química , Sulfeto de Hidrogênio/química , Ácido Hipocloroso/química , Estresse Oxidativo , Selênio/química , Absorção Fisico-Química , Animais , Derivados de Benzeno/química , Linhagem Celular , Humanos , Concentração de Íons de Hidrogênio , Espectroscopia de Ressonância Magnética , Camundongos , Microscopia Confocal , Oxirredução , Espécies Reativas de Oxigênio/química , Substâncias Redutoras/farmacologia , Espectrometria de Fluorescência , Fatores de TempoRESUMO
In this article, the sensing mechanism of a fluorescence probe for hypochloric acid, NI-Se, has been investigated using experimental and theoretical methods. Based on the results of the steady-state and time-resolved emission spectra of NI-Se and its oxidized form NI-SeO, we suggested that there was twist internal charge transfer (TICT) state with faint fluorescence in NI-Se. Subsequently, the ground and excited state minimum geometries of NI-Se and NI-SeO were optimized with DFT/TD-DFT methods. The results demonstrated there was a twisting process in the excited state of NI-Se and that this twist process was induced by the nonbonding interaction between the Se and N atoms. In addition, the calculated spectra and molecular orbitals confirmed the charge transfer character of the TICT state in NI-Se. To further investigate the driving force behind the twist in NI-Se, we synthesized NI-O, which has no Se···N nonbonding interaction, as a control sample. Herein, we also present the characterization, fluorescence properties and the optimized geometries of NI-O. Moreover, the results showed that Se···N nonbonding interaction plays a significant role in the twisting process of NI-Se.
Assuntos
Corantes Fluorescentes/química , Ácido Hipocloroso/química , Modelos Moleculares , Conformação Molecular , Nitrogênio/química , Teoria Quântica , Selênio/química , Solventes/químicaRESUMO
Based on a novel strategy for modulating the fluorescence of selenide and selenoxide, we have designed and developed a reversible fluorescent probe for hypochloric acid. And the synthesis, characterization, fluorescence properties, as well as the biological applications in living cells and animals, have all been described.
Assuntos
Corantes Fluorescentes/química , Ácido Hipocloroso/análise , Microscopia Confocal , Compostos de Selênio/química , Selênio/química , Animais , Linhagem Celular , Transporte de Elétrons , Humanos , Sulfeto de Hidrogênio/metabolismo , Íons/química , Camundongos , Óxidos de SelênioRESUMO
A diselenide containing fluorescent probe based on a fluorescein scaffold for thiols was developed. The fluorescent probe exhibited rapid response, high selectivity and reversibility. Confocal fluorescence microscopy was used to visualize the redox changes mediated by thiols and reactive oxygen species in living HeLa cells.
Assuntos
Técnicas de Química Analítica/métodos , Corantes Fluorescentes/química , Peróxido de Hidrogênio/química , Estresse Oxidativo , Selênio/química , Compostos de Sulfidrila/análise , Células HeLa , Humanos , Microscopia Confocal , Estrutura Molecular , Espectrometria de Fluorescência , Fatores de TempoRESUMO
We have developed a new reversible fluorescence probe MPhSe-BOD for the redox cycle process between hypochlorous acid and hydrogen sulfide in solution and in living cells. Confocal microscopy imaging using RAW264.7 cell lines shows that the probe has good cell membrane permeability, and can monitor intracellular HClO/H(2)S redox cycles continuously.