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首页> 外文期刊>Dalton transactions: An international journal of inorganic chemistry >Highly potent half- sandwich iridium and ruthenium complexes as lysosome- targeted imaging and anticancer agents
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Highly potent half- sandwich iridium and ruthenium complexes as lysosome- targeted imaging and anticancer agents

机译：高效的半三明治铱和钌配合物作为溶酶体靶向成像和抗癌剂

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In this study, six half-sandwich luminescent iridium (Ir) and ruthenium (Ru) anticancer complexes bearing (PP)-P-boolean AND-chelating ligands 1,2-bis(diphenylphosphino)benzene (dppbz) and 1,8-bis(diphenylphosphino)naphthalene (dppn) were synthesized and characterized via(1)H-NMR spectroscopy, P-31-NMR spectroscopy, mass spectrometry, elemental analysis and X-ray crystallography. All the complexes displayed more potent anticancer activity than cisplatin towards A549 lung cancer cells and HeLa cervical cancer cells, especially the most potent iridium complex Ir3, which was 73 times more potent than cisplatin against A549 cells. Different from cisplatin, no nucleobase adducts of Ir3 were detected. With the help of the self-luminescence of complex Ir3 and confocal microscopy, it was observed that Ir3 efficiently penetrated into the A549 cells via energy-dependent active transport, and specifically accumulated in lysosomes, affected the permeabilization of the lysosomal membranes and induced caspase-dependent cell death through lysosomal damage. Both apoptosis and autophagy of the A549 cells were observed. The reactive oxygen species (ROS) elevation, reduction of the mitochondrial membrane potential and cell cycle arrest at the G(0)/G(1) phase also contributed to the observed cytotoxicity of Ir3. We demonstrate that these half-sandwich Ir and Ru anticancer complexes have different anticancer mechanism of action from that of cisplatin, which can be developed as potential multifunctional theranostic platforms that combine bioimaging and anticancer capabilities.
机译：在这项研究中，六个半三明治发光铱（IR）和钌（Ru）抗癌复合物轴承（PP）-P-Boolean和Chelating配体1,2-双（二苯基膦基）苯（DPPBZ）和1,8-BIS （二苯基膦酰基）萘（DPPN）被合成并通过（1）H-NMR光谱，P-31-NMR光谱，质谱，元素分析和X射线晶体学。所有复合物都显示出比顺铂的抗癌活动更多的抗癌活性，朝向A549肺癌细胞和Hela宫颈癌细胞，特别是最有效的铱络合物IR3，比对A549细胞的顺铂更有效的效力73倍。与顺铂不同，检测到IR3的核碱基加合物。借助于复合IR3和共聚焦显微镜的自发光，观察到IR3通过能量依赖性的活性转运有效地渗透到A549细胞中，并在溶酶体中累积，影响了溶酶体膜的渗透性和诱导的Caspase-通过溶酶体损伤依赖细胞死亡。观察到A549细胞的凋亡和自噬。在G（0）/ g（1）相的电池膜电位和细胞周期停滞的反应性氧物质（ROS）升高也有助于IR3的观察到的细胞毒性。我们证明，这些半三明治IR和Ru抗癌复合物具有不同于顺铂的抗癌机制，可作为结合生物体和抗癌能力的潜在多功能治疗平台开发。

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    Li JuanJuan; Tian Zhenzhen; Xu Zhishan; Zhang Shumiao; Feng Yaqian; Zhang Lingdong; Liu Zhe;

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    Qufu Normal Univ Inst Anticanc Agents Dev &

    Theranost Applicat Key Lab Life Organ Anal Qufu 273165 Peoples R China;

    Qufu Normal Univ Inst Anticanc Agents Dev &

    Theranost Applicat Key Lab Life Organ Anal Qufu 273165 Peoples R China;

    Qufu Normal Univ Inst Anticanc Agents Dev &

    Theranost Applicat Key Lab Life Organ Anal Qufu 273165 Peoples R China;

    Qufu Normal Univ Inst Anticanc Agents Dev &

    Theranost Applicat Key Lab Life Organ Anal Qufu 273165 Peoples R China;

    Qufu Normal Univ Inst Anticanc Agents Dev &

    Theranost Applicat Key Lab Life Organ Anal Qufu 273165 Peoples R China;

    Qufu Normal Univ Inst Anticanc Agents Dev &

    Theranost Applicat Key Lab Life Organ Anal Qufu 273165 Peoples R China;

    Qufu Normal Univ Inst Anticanc Agents Dev &

    Theranost Applicat Key Lab Life Organ Anal Qufu 273165 Peoples R China;

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  • 正文语种 eng
  • 中图分类 化学;无机化学;
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