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1.
目的 基于前期研究表明二氢卟吩f的3-乙烯基成醚修饰具有更强的光敏抗肿瘤活性而设计合成二氢卟吩p6醚类光敏剂(1),研究其初步体外光动力抗癌活性。方法 以蚕沙叶绿素a粗提物酸水解产物脱镁叶绿酸a(5)经碱及空气氧化降解制得的紫红素-18(4)为先导物,通过碱水解和CH2N2甲基化制得二氢卟吩p6三甲酯(2),2与33% HBr加成后再和烷氧醇发生亲核取代反应生成目标化合物(1),并评价其对黑色素瘤B16-F10细胞的光动力杀伤效应。结果 6个目标化合物1a-1f对黑色素瘤B16-F10细胞的体外光动力抗癌活性均优于同类阳性对照药他拉泊芬和维替泊芬,其结构经电喷雾质谱(ESI-MS)、氢谱(1H NMR)、碳谱(13C NMR)及电喷雾高分辨质谱(ESI-HRMS)确证。结论 二氢卟吩p6醚类光敏剂具有光动力抗癌活性强、治疗指数(暗毒/光毒比)高等优点,值得进一步开发研究。 相似文献
2.
Antibacterial photodynamic treatment of periodontopathogenic bacteria with indocyanine green and near‐infrared laser light enhanced by TroloxTM 下载免费PDF全文
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Photodynamic therapy (PDT) has received considerable attention as a therapeutic treatment for cancer and other diseases; however, it is frequently accompanied by prolonged phototoxic reaction of the skin due to slow clearance of synthetic photosensitizers (PSs) administered externally. This study was designed to investigate the genetic use of pKillerRed-mem, delivered using complexes of chitosan (CS) and poly(γ-glutamic acid) (γPGA), to intracellularly express a membrane-targeted KillerRed protein that can be used as a potential PS for PDT. Following transfection with CS/pKillerRed/γPGA complexes, a red fluorescence protein of KillerRed was clearly seen at the cellular membranes. When exposed to green-light irradiation, the KillerRed-positive cells produced an excessive amount of reactive oxygen species (ROS) in a time-dependent manner. Data from viability assays indicate that ROS have an important role in mediating KillerRed-induced cytotoxicity, apoptosis, and anti-proliferation, suggesting that KillerRed can be used as an intrinsically generated PS for PDT treatments. Notably, the phototoxic reaction of KillerRed toward cells gradually became negligible over time, presumably because of its intracellular degradability. These experimental results demonstrate that this genetically encoded KillerRed is biodegradable and has potential for PDT-induced destruction of diseased cells. 相似文献
5.
Zhenzhi Shi Wenzhi Ren An Gong Xinmei Zhao Yuehong Zou Eric Michael Bratsolias Brown Xiaoyuan Chen Aiguo Wu 《Biomaterials》2014
Photodynamic therapy (PDT) is a promising treatment modality for cancer and other malignant diseases, however safety and efficacy improvements are required before it reaches its full potential and wider clinical use. Herein, we investigated a highly efficient and safe photodynamic therapy procedure by developing a high/low power density photodynamic therapy mode (high/low PDT mode) using methoxypoly(ethylene glycol) thiol (mPEG-SH) modified gold nanorod (GNR)-AlPcS4 photosensitizer complexes. mPEG-SH conjugated to the surface of simple polyelectrolyte-coated GNRs was verified using Fourier transform infrared spectroscopy; this improved stability, reduced cytotoxicity, and increased the encapsulation and loading efficiency of the nanoparticle dispersions. The GNR-photosensitizer complexes were exposed to the high/low PDT mode (high light dose = 80 mW/cm2 for 0.5 min; low light dose = 25 mW/cm2 for 1.5 min), and a high PDT efficacy leads to approximately 90% tumor cell killing. Due to synergistic plasmonic photothermal properties of the complexes, the high/low PDT mode demonstrated improved efficacy over using single wavelength continuous laser irradiation. Additionally, no significant loss in viability was observed in cells exposed to free AlPcS4 photosensitizer under the same irradiation conditions. Consequently, free AlPcS4 released from GNRs prior to cellular entry did not contribute to cytotoxicity of normal cells or impose limitations on the use of the high power density laser. This high/low PDT mode may effectively lead to a safer and more efficient photodynamic therapy for superficial tumors. 相似文献
6.
《Islets》2013,5(4)
Disturbances in pulsatile insulin secretion and Ca2+ oscillations in pancreatic β-cells are early markers of diabetes, but the underlying mechanisms are still incompletely understood. Reactive oxygen/nitrogen species (ROS/RNS) are implicated in reduced β-cell function, and ROS/RNS target several Ca2+ pumps and channels. Thus, we hypothesized that ROS/RNS could disturb Ca2+ oscillations and downstream insulin pulsatility. We show that ROS/RNS production by photoactivation of aluminum phthalocyanine chloride (AlClPc) abolish or accelerate Ca2+ oscillations in the MIN6 β-cell line, depending on the amount of ROS/RNS. Application of the sarcoplasmic/endoplasmic reticulum Ca2+ ATPase (SERCA) inhibitor thapsigargin modifies the Ca2+ response to high concentrations of ROS/RNS. Further, thapsigargin produces effects that resemble those elicited by moderate ROS/RNS production. These results indicate that ROS/RNS interfere with endoplasmic reticulum Ca2+ handling. This idea is supported by theoretical studies using a mathematical model of Ca2+ handling adapted to MIN6 cells. Our results suggest a putative link between ROS/RNS and disturbed pulsatile insulin secretion. 相似文献
7.
本文就近年来光敏剂与放疗结合的相关临床和实验研究的进展情况做了较详细的阐述,并明确指出其放疗增敏机制,及开展多中心试验研究以证实其放疗增敏作用是今后的研究方向。 相似文献
8.
Del Governatore M Hamblin MR Piccinini EE Ugolini G Hasan T 《British journal of cancer》2000,82(1):56-64
The goal of this study was to develop a strategy for the selective destruction of colorectal cancer cells. Towards this end, photoimmunoconjugates were prepared between the anti-colon cancer monoclonal antibody 17.1A and the photosensitizer (PS) chlorin(e6) (c(e6)). Polylysine linkers bearing several c(e6) molecules were covalently attached in a site-specific manner to partially reduced IgG molecules, which allowed photoimmunoconjugates to bear either cationic or anionic charges. The conjugates retained immunoreactivity as shown by enzyme-linked immunosorbent assays and by competition studies with native antibody. The overall charge on the photoimmunoconjugate was an important determinant of PS delivery. The cationic photoimmunoconjugate delivered 4 times more c(e6) to the cells than the anionic photoimmunoconjugate, and both 17.1A conjugates showed, in comparison to non-specific rabbit IgG conjugates, selectivity for antigen-positive target cells. Illumination with only 3 J cm(-2) of 666 nm light reduced the number of colony forming cells by more than 90% for the cationic 17.1A conjugate and by 73% for the anionic 17.1A conjugate after incubation with 1 microM c(e6) equivalent of the respective conjugates. By contrast, 1 microM free c(e6) gave only a 35% reduction in colonies. These data suggest photoimmunoconjugates may have applications in photoimmunotherapy where destruction of colorectal cancer cells is required. 相似文献
9.
Kaviani A Ataie-Fashtami L Fateh M Sheikhbahaee N Ghodsi M Zand N Djavid GE 《Lasers in surgery and medicine》2005,36(5):377-382
BACKGROUND AND OBJECTIVES: We aimed to treat different pathologic types of basal cell carcinomas (BCCs) using photodynamic therapy (PDT). STUDY DESIGN/MATERIALS AND METHODS: Thirty lesions in six patients underwent PDT. The photosensitizer used was Photoheme, a hematoporphyrin derivative IX. It was injected intravenously at the dose of 2-3.25 mg/kg. After 24 hours, the lesions were illuminated by laser light (lambda = 632 nm, light exposure dose = 100-200 J/cm2). Lesions were evaluated pre and post-operatively and at follow-up sessions (of up to 6 months). RESULTS: After a single session of PDT, the average response rate in different histopathologic kinds of basal cell carcinoma (e.g., ulcerative, superficial, nodular, and pigmented forms) were 100%, 62%, 90%, and 14%, respectively. In patients who responded completely, the cosmetic results were excellent and there were no recurrence at 6th month of follow-up. CONCLUSION: Although PDT seems to be an effective treatment modality for superficial, ulcerative, and nodular BCCs, it is not recommended for pigmented lesions. 相似文献
10.
Neumann NJ Hanneken S Ruzicka T Lehmann P 《Photodermatology, photoimmunology & photomedicine》2004,20(5):224-229
BACKGROUND: Oxygen, appropriate light sources, and special photosensitizers are necessary to induce photochemical damage in tumor cells via photodynamic therapy (PDT) delta-aminolevulinic acid (ALA) is increasingly used in PDT, because topical or systemic administration of ALA induces accumulation of endogenous porphyrins preferentially in neoplastic tissues. Subsequent radiation with light of approximately 630 nm leads to selective damage of tumor cells. PDT should optimally leave peritumoral tissues unaffected, but only few data are reported on the effects and the time course of ALA-induced porphyrins in tumor-free tissues. METHODS: Therefore, we studied the phototoxic effects of protoporphyrin IX (PP) and ALA-induced porphyrins in a recently established phototoxic model based on tumor-free tissue, the photo hen's egg test (PHET). RESULTS: Employing this test procedure, PP provoked strong phototoxic reactions when irradiated with Ultraviolet A immediately and up to 30 h after substance application. In contrast, ALA induced a significant phototoxic effect only if irradiated 24 h after application. CONCLUSION: Thus, we observed a delayed phototoxic effect of ALA in tumor-free tissue of the yolk sac (YS) blood vessel system. This delayed phototoxic response 24 h after ALA application is probably caused by endogenously synthesized porphyrins. In contrast, epithelial tumors show a maximum porphyrin accumulation 4-8 h after ALA application whereas in healthy human skin porphyrin synthesis is less intensive but prolonged with maximum levels 24-48 h after ALA application. Thus, ALA induced virtually the same delayed phototoxic effect in the tumor-free YS blood vessel tissue as in healthy human skin. These results show that the PHET is a useful model for the predictive preclinical risk assessment of exogenous or endogenous photosensitizers. 相似文献