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11.
The roles played by singlet oxygen (1O2) in photodynamic therapy are not fully understood yet. In particular, the mobility of 1O2 within cells has been a subject of debate for the last two decades. In this work, we report on the kinetics of 1O2 formation, diffusion, and decay in human skin fibroblasts. 1O2 has been photosensitized by two water-soluble porphyrins targeting different subcellular organelles, namely the nucleus and lysosomes, respectively. By recording the time-resolved near-IR phosphorescence of 1O2 and that of its precursor the photosensitizer's triplet state, we find that the kinetics of singlet oxygen formation and decay are strongly dependent on the site of generation. 1O2 photosensitized in the nucleus is able to escape out of the cells while 1O2 photosensitized in the lysosomes is not. Despite showing a lifetime in the microsecond time domain, 1O2 decay is largely governed by interactions with the biomolecules within the organelle where it is produced. This observation may reconcile earlier views that singlet oxygen-induced photodamage is highly localized, while its lifetime is long enough to diffuse over long distances within the cells. 相似文献
12.
Frédéric Schmitt Padavattan Govindaswamy Olivier Zava Georg Süss-Fink Lucienne Juillerat-Jeanneret Bruno Therrien 《Journal of biological inorganic chemistry》2009,14(1):101-109
Mononuclear 5-(4-pyridyl)-10,15,20-triphenylporphyrin and 5-(3-pyridyl)-10,15,20-triphenylporphyrin as well as tetranuclear
5,10,15,20-tetra(4-pyridyl)porphyrin (tetra-4-pp) and 5,10,15,20-tetra(3-pyridyl)porphyrin) (tetra-3-pp) arene ruthenium(II)
derivatives (arene is C6H5Me or p-Pr
i
C6H4Me) were prepared and evaluated as potential dual photosensitizers and chemotherapeutics in human Me300 melanoma cells. In
the absence of light, all tetranuclear complexes were cytotoxic (IC50 ≤ 20 μM), while the mononuclear derivatives were not (IC50 ≥ 100 μM). Kinetic studies of tritiated thymidine and tritiated leucine incorporations in cells exposed to a low concentration
(5 μM) of tetranuclear p-cymene derivatives demonstrated a rapid inhibition of DNA synthesis, while protein synthesis was inhibited only later, suggesting
arene ruthenium–DNA interactions as the initial cytotoxic process. All complexes exhibited phototoxicities toward melanoma
cells when exposed to laser light of 652 nm. At low concentration (5 μM), LD50 of the mononuclear derivatives was between 5 and 10 J/cm2, while for the tetranuclear derivatives LD50 was approximately 2.5 J/cm2 for the [Ru4(η6-arene)4(tetra-4-pp)Cl8] complexes and less than 0.5 J/cm2 for the [Ru4(η6-arene)4(tetra-3-pp)Cl8] complexes. Examination of cells under a fluorescence microscope revealed the [Ru4(η6-arene)4(tetra-4-pp)Cl8] complexes as cytoplasmic aggregates, whereas the [Ru4(η6-arene)4(tetra-3-pp)Cl8] complexes were homogenously dispersed in the cytoplasm. Thus, these complexes present a dual synergistic effect with good
properties of both the arene ruthenium chemotherapeutics and the porphyrin photosensitizer. 相似文献
13.
For many biological and biomedical studies, it is essential to detect the production of 1O2 and quantify its production yield. Among the available methods, detection of the characteristic 1270-nm phosphorescence of singlet oxygen by time-resolved near-infrared (TRNIR) emission constitutes the most direct and unambiguous approach. An alternative indirect method is electron paramagnetic resonance (EPR) in combination with a singlet oxygen probe. This is based on the detection of the TEMPO free radical formed after oxidation of TEMP (2,2,6,6-tetramethylpiperidine) by singlet oxygen. Although the TEMPO/EPR method has been widely employed, it can produce misleading data. This is demonstrated by the present study, in which the quantum yields of singlet oxygen formation obtained by TRNIR emission and by the TEMPO/EPR method are compared for a set of well-known photosensitizers. The results reveal that the TEMPO/EPR method leads to significant overestimation of singlet oxygen yield when the singlet or triplet excited state of the photosensitizer is efficiently quenched by TEMP, acting as electron donor. In such case, generation of the TEMP+ radical cation, followed by deprotonation and reaction with molecular oxygen, gives rise to an EPR-detectable TEMPO signal that is not associated with singlet oxygen production. This knowledge is essential for an appropriate and error-free application of the TEMPO/EPR method in chemical, biological, and medical studies. 相似文献
14.
目的:观察新型激光光敏根管消毒剂、甲苯胺蓝和亚甲基蓝在牙本质中的渗透效果,评价三种光敏剂在牙本质中的渗透性。方法:收集新鲜拔除的离体单根管牙90颗,根管预备后随机分为三组。每组30颗。A组为新型激光光敏根管消毒剂组;B组为甲苯胺蓝组;c组为亚甲基蓝组。A、B、C三组实验根管内分别用浸有饱和的新型激光光敏根管消毒剂、甲苯胺蓝和亚甲基蓝的棉捻在根管内停留60秒。沿牙体长轴颊舌纵向劈开,倒置荧光显微镜下观察并拍照,用Photoshop8.01软件测量三种光敏剂渗透入牙本质的平均深度。结果:新型激光光敏根管消毒剂在牙本质内的渗透平均深度为553.25μm,甲苯胺蓝在牙本质内的渗透平均深度为350.75μm,亚甲基蓝在牙本质内的渗透平均深度为168.25μm。结论:新型激光光敏根管消毒剂在牙本质渗透性明显优于甲苯胺蓝和亚甲基蓝,具有良好的牙本质渗透性。 相似文献
15.
Real-time investigation of molecular recognition between protein and the photosensitizer of photodynamic therapy (PDT) was carried out by a quartz crystal microbalance (QCM) sensor integrated into a flow injection analysis (FIA) system. The photosensitizer meso-tetrakis(4-hydroxyphenyl)porphyrin (p-THPP) was immobilized on the gold electrode of the QCM chip by combining the sol-gel and self-assembly methods. Such a rapid screen analysis of molecular recognition showed that the p-THPP-immobilized sensor exhibited sensitive and specific interaction only with hemoglobin (Hb). The kinetic rate constants (kass and kdiss) and the equilibrium association constant (KA) for p-THPP-Hb interaction were calculated by linear regression. The sensing performance characteristics of the proposed sensor were investigated. The sensor showed excellent selectivity, reproducibility, and repeatability for the detection of Hb. A linear calibration plot was obtained over a range from 0.2 to 1.0 μM with a detection limit (signal/noise ratio = 3) of 0.15 μM. The response mechanism of the sensor is discussed in detail. Due to its low cost and simple manipulation, this QCM-FIA system was shown to be a highly effective method for the investigation of interaction between biomacromolecules and the PDT photosensitizer. It also provides a potential strategy for screening an efficient and less harmful photosensitizer for PDT application. 相似文献
16.
Wei Zhu Lai-Xing Wang Dan-Ye Chen Ying-Hua Gao Yi-Jia Yan Xiao-Feng Wu Mi Wang Yi-Ping Han Zhi-Long Chen 《Bioorganic & medicinal chemistry letters》2018,28(16):2784-2788
Three novel 173-dicarboxylethyl-pyropheophorbide-a amide derivatives as photosensitizers for photodynamic therapy (PDT) were synthesized from pyropheophorbide-a (Ppa). Their photophysical and photochemical properties, intracellular localization, photocytotoxicity in vitro and in vivo were investigated. All target compounds exhibited low cytotoxicity in the dark and remarkable photocytotoxicity against human esophageal cancer cells. Among them, 1a showed highest singlet oxygen quantum yield. Upon light activation, 1a exhibited significant photocytotoxicity. After PDT treatment, the growth of Eca-109 tumor in nude mice was significantly inhibited. Therefore, 1a is a powerful and promising antitumor photosensitizer for PDT. 相似文献
17.
Sebastian A. Thompson Amit Aggarwal Sunaina Singh Alejandro P. Adam Joao P.C. Tome Charles Michael Drain 《Bioorganic & medicinal chemistry》2018,26(18):5224-5228
Photodynamic therapy (PDT) is a non-invasive treatment widely applied to different cancers. The goal of PDT is the photo-induced destruction of cancer cells by the activation of different cell death mechanisms, including apoptosis and/or necrosis. Recent efforts focusing on understanding the mechanisms of cell death activated by PDT find that it depends on the type of photosensitizer (PS), targeted organelles, and nature of the light used. It is generally accepted that very short incubation times are required to direct the PS to the plasma membrane (PM), while longer periods result in the accumulation of the PS in internal compartments such as the endoplasmic reticulum or mitochondria. Glycosylation of the PS targets cancer via saccharide receptors on the cell surface, and is generally assumed that these compounds rapidly internalize and accumulate, e.g. in the endoplasmic reticulum. Herein we demonstrate that a minor fraction of a glycosylated chlorin compound residing at the PM of cancer cells can activate necrosis upon illumination by compromising the PM independently of the length of the incubation period. The results presented here show that the PM can also be targeted by glycosylated PS designed to accumulate in internal organelles. PS activation to induce necrosis by compromising the plasma membrane has the benefits of fast cell death and shorter irradiation times. The findings described here expand our understanding of the cellular damage induced by phototherapies, presenting the possibility of activating another cell death mechanism based on the incubation time and type of light used. 相似文献
18.
de Souza AC Kodach L Gadelha FR Bos CL Cavagis AD Aoyama H Peppelenbosch MP Ferreira CV 《Apoptosis : an international journal on programmed cell death》2006,11(10):1761-1771
Besides having a pivotal biological function as a component of coenzymes, riboflavin appears a promissing antitumoral agent,
but the underlying molecular mechanism remains unclear. In this work, we demonstrate that irradiated riboflavin, when applied
at μM concentrations, induces an orderly sequence of signaling events finally leading to leukemia cell death. The molecular
mechanism involved is dependent on the activation of caspase 8 caused by overexpression of Fas and FasL and also on mitochondrial
amplification mechanisms, involving the stimulation of ceramide production by sphingomyelinase and ceramide synthase. The
activation of this cascade led to an inhibition of mitogen activated protein kinases: JNK, MEK and ERK and survival mediators
(PKB and IAP1), upregulation of the proapoptotic Bcl2 member Bax and downregulation of cell cycle progression regulators.
Importantly, induction of apoptosis by irradiated riboflavin was leukaemia cell specific, as normal human lymphocytes did
not respond to the compound with cell death. Our data indicate that riboflavin selectively activates Fas cascade and also
constitutes a death receptor-engaged drug without harmful side effects in normal cells, bolstering the case for using this
compound as a novel avenue for combating cancerous disease. 相似文献
19.
Kuroda A Nakashima T Yamaguchi K Oda T 《Comparative biochemistry and physiology. Toxicology & pharmacology : CBP》2005,141(3):297-305
Chattonella marina (C. marina), a raphidophycean flagellate, is a causative organism of red tide, and highly toxic to fish. In this study, we found that the cell-free methanol extract prepared from this flagellate exhibited potent hemolytic activity against rabbit erythrocytes. Interestingly, the hemolytic activity of the extract was absolutely light-dependent, and no hemolytic activity was detected in the dark even at very high concentration. Gel filtration chromatography of the methanol extract on a column of Sephadex LH-20 revealed that the extract contained hemagglutinin as well as hemolytic agents, and the substances responsible for these activities were separately eluted. These results suggest that the hemagglutinating and hemolytic activities were derived from distinct compounds. The hemolytic fraction obtained after gel filtration (F4) caused marked inhibition of the growth of C. marina itself and other species of phytoplanktons. Furthermore, F4 showed a potent cytotoxicity toward various mammalian cultured cell lines including human tumor cells (HeLa cells) in a dose-dependent manner. The cytotoxicity was also light-dependent, and no cytotoxic effect was exhibited in any cell lines tested in the dark. After further purification procedures via preparative thin-layer chromatography and subsequent HPLC, a major hemolytic agent was obtained as highly purified form. Since the methanol extracts prepared from other raphidophycean flagellates such as Heterosigma akashiwo, Olisthodiscus luteus, and Fibrocapsa japonica showed light-dependent hemolytic activity toward rabbit erythrocytes, it was suggested that the light-dependent hemolytic agents commonly exist at least in these raphidophycean flagellates. 相似文献
20.
《Bioorganic & medicinal chemistry》2020,28(7):115355
Photodynamic therapy (PDT) is considered a promising strategy for cancer treatment. PDT utilizes light in combination with a photosensitizer (PS) to induce several phototoxic reactions. Phthalocyanines (Pcs), a second generation of photosensitizers, have been studied in several cancer models. Among these, Pcs, have become of interest for the treatment of glioblastomas which are one of the most common and aggressive forms of tumors of the central nervous system. Due to the lipophilic nature of Pcs and their limited solubility in water, Pcs can be loaded in liposomes. In this work, we characterized liposomes of ZnPc and TAZnPc and their effectiveness to photoinactivate glioblastoma cells, was evaluated. Both Pcs show an increase in their photosensitizing activity when they were administrated in Dipalmitoylphosphatidylcholine-cholesterol liposomes compared to Pcs administrated in dimethylformamide. 相似文献