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首页> 外文期刊>Coordination chemistry reviews >Ru(Ⅱ) dyads derived from α-oligothiophenes: A new class of potent and versatile photosensitizers for PDT
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Ru(Ⅱ) dyads derived from α-oligothiophenes: A new class of potent and versatile photosensitizers for PDT

机译:α-寡聚噻吩衍生的Ru(Ⅱ)二联体:一类新型的PDT强效多功能光敏剂

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摘要

Ru(Ⅱ) dyads derived from organic units that impart low-lying ~3IL excited states combine the most attractive features of organic photosensitizers with those of coordination complexes. The result is a bichromophoric system with excited-state lifetimes that are significantly longer than those associated with traditional ~3MLCT states. Incorporation of α-oligothiophenes asthe organic chromophore leads to systems that act as dual Type Ⅰ/Ⅱ photosensitizers, opening up the possibility of treating hypoxic tumors with photodynamic therapy (PDT) and overcoming problems with in vivo dosimetry. These photosensitizers, particularly those that consist of three thiophene units and higher, are remarkable DNA binders and photocleavers when exposed to light, exhibiting no interference with DNA structural integrity in the absence of a light-trigger. Such light-responsive agents localize in the nuclei of cells without the need for a carrier and produce a potent PDT response with minimal dark toxicity. This phototherapeutic effect translates directly to animals and is superior to the clinical agent Photofrin~® in this model. These Ru(Ⅱ) dyads can be activated with light in the PDT window, despite very low molar extinction coefficients in this region, and this phenomenon can be attributed to the efficiency with which these agents operate. The ability to activate these prodrugs with ultraviolet to near-infrared light marks an unprecedented versatility that can be exploited to match treatment depth to tumor invasion depth without compromising potency, giving rise to photosensitizers for multiwavelength PDT.
机译:来自赋予低位〜3IL激发态的有机单元的Ru(Ⅱ)二元化合物将有机光敏剂的最吸引人的特征与配位配合物的特征相结合。结果是双色系统的激发态寿命比传统的〜3MLCT态要长得多。引入α-低聚噻吩作为有机生色团导致系统充当双重Ⅰ/Ⅱ型光敏剂,为光动力疗法(PDT)治疗缺氧肿瘤提供了可能性,并克服了体内剂量测定法的问题。这些光敏剂,特别是那些由三个噻吩单元及更高的噻吩组成的光敏剂,在暴露于光下时是显着的DNA结合剂和光切割剂,在没有光触发的情况下不会干扰DNA结构完整性。此类光响应剂无需载体即可定位于细胞核中,并产生有效的PDT反应,且暗毒性最小。这种光疗作用可直接转化为动物,并且在该模型中优于临床药物Photofrin®。尽管在该区域摩尔消光系数非常低,但这些Ru(Ⅱ)二重体仍可以在PDT窗口中被光激活,并且这种现象可以归因于这些试剂的有效操作。利用紫外线到近红外光激活这些前药的能力,标志着前所未有的多功能性,可以利用它使治疗深度与肿瘤浸润深度相匹配而又不影响效能,从而产生了用于多波长PDT的光敏剂。

著录项

  • 来源
    《Coordination chemistry reviews》 |2015年第1期|127-138|共12页
  • 作者单位

    Department of Chemistry, Acadia University, 6 University Avenue, Wolfville, NS B4P 2R6, Canada;

    Department of Chemistry, Acadia University, 6 University Avenue, Wolfville, NS B4P 2R6, Canada;

    Department of Chemistry, Acadia University, 6 University Avenue, Wolfville, NS B4P 2R6, Canada;

    Department of Chemistry, Acadia University, 6 University Avenue, Wolfville, NS B4P 2R6, Canada;

    Theralase Technologies, Inc., 1945 Queen Street East, Toronto, ON M4L 1H7, Canada;

    Theralase Technologies, Inc., 1945 Queen Street East, Toronto, ON M4L 1H7, Canada;

    Department of Chemistry, Acadia University, 6 University Avenue, Wolfville, NS B4P 2R6, Canada;

    Department of Chemistry, Acadia University, 6 University Avenue, Wolfville, NS B4P 2R6, Canada;

    Department of Chemistry, Acadia University, 6 University Avenue, Wolfville, NS B4P 2R6, Canada;

    Department of Chemistry, Acadia University, 6 University Avenue, Wolfville, NS B4P 2R6, Canada;

    Theralase Technologies, Inc., 1945 Queen Street East, Toronto, ON M4L 1H7, Canada;

    Department of Medical Biophysics, Princess Margaret Cancer Centre/University of Toronto, 101 College Street, Toronto, ON M5G 1C7, Canada;

    Department of Chemistry, Acadia University, 6 University Avenue, Wolfville, NS B4P 2R6, Canada;

  • 收录信息 美国《科学引文索引》(SCI);美国《生物学医学文摘》(MEDLINE);
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

    Photodynamic therapy; Photosensitizers; Metal complexes; α-Oligothiophenes; DNA damage; Nuclear targeting;

    机译:光动力疗法;光敏剂;金属络合物;α-寡噻吩;DNA损伤;核靶向;

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