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首页> 外文期刊>Photodiagnosis and Photodynamic Therapy >The effects of protoporphyrin IX-induced photodynamic therapy with and without iron chelation on human squamous carcinoma cells cultured under normoxic, hypoxic and hyperoxic conditions
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The effects of protoporphyrin IX-induced photodynamic therapy with and without iron chelation on human squamous carcinoma cells cultured under normoxic, hypoxic and hyperoxic conditions

机译：原卟啉IX诱导的光动力学疗法在有氧和无氧条件下对人鳞状细胞的影响

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摘要

Background: Photodynamic therapy requires the combined interaction of a photosensitiser, light and oxygen to ablate target tissue. In this study we examined the effect of iron chelation and oxygen environment manipulation on the accumulation of the clinically useful photosensitiser protoporphyrin IX (PplX) within human squamous epithelial carcinoma cells and the subsequent ablation of these cells on irradiation. Methods: Cells were incubated at concentrations of 5%, 20% or 40% oxygen for 24 h prior to and for 3 h following the administration of the PplX precursors aminolevulinic acid (ALA), methyl aminolevulinate (MAL) or hexylaminolevulinate (HAL) with or without the iron chelator 1,2-diethyl-3-hydroxypyridin-4-one hydrochloride (CP94). PplX accumulation was monitored using a fluorescence plate reader, cells were irradiated with 37J/cm~2 red light and cell viability measured using the neutral red uptake assay. Results: Manipulation of the oxygen environment and/or co-administration of CP94 with PplX precursors resulted in significant changes in both PplX accumulation and photobleaching. Incubation with 5% or 40% oxygen produced the greatest levels of PplX and photobleaching in cells incubated with ALA/MAL. Incorporation of CP94 also resulted in significant decreases in cell viability following administration of ALA/AAAL/HAL, with oxygen concentration predominantly having a significant effect in cells incubated with HAL. Conclusions: Experimentation with human squamous epithelial carcinoma cells has indicated that the iron chelator CP94 significantly increased PplX accumulation induced by each PplX congener investigated (ALA/MAL/HAL) at all oxygen concentrations employed (5%/20%/40%) resulting in increased levels of photobleaching and reduced cell viability on irradiation. Further detailed investigation of the complex relationship of PDT cytotoxicity at various oxygen concentrations is required. It is therefore concluded that iron chelation with CP94 is a simple protocol modification with which it may be much easier to enhance clinical PDT efficacy than the complex and less well understood process of oxygen manipulation.
机译：背景：光动力疗法需要光敏剂，光和氧气的共同作用来消融靶组织。在这项研究中，我们研究了铁螯合和氧气环境操作对人鳞状上皮癌细胞内临床有用的光敏剂原卟啉IX（PplX）积累的影响，以及随后在辐射下对这些细胞的消融作用。方法：将PplX前体氨基乙酰丙酸（ALA），氨基乙酰丙酸甲酯（MAL）或己基氨基乙酰丙酸酯（HAL）与PplX前体一起在5％，20％或40％氧气浓度下孵育细胞24小时和3小时。或不使用铁螯合剂1,2-二乙基-3-羟基吡啶-4-盐酸盐（CP94）。使用荧光板读数器监测PplX的积累，用37J / cm〜2的红光照射细胞，并使用中性红吸收测定法测量细胞活力。结果：氧气环境的操纵和/或CP94与PplX前体的共同施用导致PplX积累和光致漂白的显着变化。在与ALA / MAL一起孵育的细胞中，与5％或40％的氧气一起孵育会产生最高水平的PplX和光漂白。在施用ALA / AAAL / HAL后，CP94的掺入还导致细胞活力的显着降低，其中氧浓度在与HAL孵育的细胞中主要具有显着的作用。结论：对人鳞状上皮癌细胞的实验表明，铁螯合剂CP94在所有使用的氧气浓度（5％/ 20％/ 40％）下均显着提高了每种研究的PplX同系物（ALA / MAL / HAL）诱导的PplX积累，从而导致增加了光漂白水平，降低了照射后的细胞活力。需要进一步研究各种氧浓度下PDT细胞毒性的复杂关系。因此得出的结论是，与CP94进行铁螯合是一种简单的方案修饰，通过它可以比复杂且鲜为人知的氧气处理过程更容易增强临床PDT的功效。

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  • 来源
    《Photodiagnosis and Photodynamic Therapy》 |2013年第4期|575-582|共8页
  • 作者

    Emma Blake; James Allen; Alison Curnow;

  • 作者单位

    Clinical Photobiology, European Centre for Environment and Human Health, University of Exeter MedicalSchool, University of Exeter, Knowledge Spa, Royal Cornwall Hospital, Truro, Cornwall TR1 3HD, UK;

    Clinical Photobiology, European Centre for Environment and Human Health, University of Exeter MedicalSchool, University of Exeter, Knowledge Spa, Royal Cornwall Hospital, Truro, Cornwall TR1 3HD, UK;

    Clinical Photobiology, European Centre for Environment and Human Health, University of Exeter MedicalSchool, University of Exeter, Knowledge Spa, Royal Cornwall Hospital, Truro, Cornwall TR1 3HD, UK;

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  • 原文格式 PDF
  • 正文语种 eng
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  • 关键词

    Photodynamic therapy; Oxygen manipulation; Iron chelation; CP94; Protoporphyrin IX;

    机译：光动力疗法;氧气处理;铁螯合;CP94;原卟啉IX;

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