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首页> 外文期刊>Biomaterials Science >A water-soluble octahedral molybdenum cluster complex as a potential agent for X-ray induced photodynamic therapy
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A water-soluble octahedral molybdenum cluster complex as a potential agent for X-ray induced photodynamic therapy

机译：水溶性八面体钼簇复合物作为X射线诱导光动力疗法的潜在剂

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X-ray-induced photodynamic therapy (X-PDT) has recently evolved into a suitable modality to fight cancer. This technique, which exploits radiosensitizers producing reactive oxygen species, allows for a reduction of the radiation dose needed to eradicate cancer in the frame of the radiotherapy treatment of deep tumors. The use of transition metal complexes able to directly produce singlet oxygen, O_2(~1Δ_g), upon X-ray irradiation constitutes a promising route towards the optimization of the radiosensitizer's architecture. In our endeavour to conceive pertinent agents for X-PDT, we designed an octahedral molybdenum cluster complex (Mo_6) with iodine inner ligands, and carboxylated apical ligands bearing ethylene oxide organic functions. The sodium salt of this complex is highly soluble in aqueous media and displays red luminescence which is efficiently quenched by oxygen to produce O_2(~1Δ_g) in a high quantum yield. Furthermore, due to its high radiodensity, the complex exhibits radioluminescence in aqueous media, with the same spectral features as for photoluminescence, indicating the production of O_2(~1Δ_g) upon X-ray irradiation. The uptake of the complex by Hep-2 and MRC-5 cells is negligible during the first hours of incubation, then considerably increases in connection with the hydrolysis of the apical ligands. The complex exhibits low toxicity in vitro and induces a radiotoxic effect, noticeable against cancerous Hep-2 cells but negligible against normal MRC-5 cells, at X-ray doses that do not affect cell viability otherwise. The first evaluation of in vivo toxicity of an Mo_6 complex on a mouse model evidences a moderate and delayed toxic effect on kidneys, with an intravenous LD_(50) value of 390 ± 30 mg kg~(-1), possibly connected with hydrolysis-induced aggregation of the complex. Overall, this complex displays attractive features as a singlet oxygen radiosensitizer for X-PDT, highlighting the potential of transition metal cluster complexes towards this modality.
机译：X射线诱导的光动力疗法（X-PDT）最近进化成适当的癌症态度。这种利用产生反应性氧物质的放射胶质剂的技术允许减少在深肿瘤的放射治疗框架中消除癌症所需的辐射剂量。在X射线照射时，使用能够直接产生单线氧的过渡金属配合物O_2（〜1Δ_g）构成了朝向优化放射敏化器的架构的有希望的路线。在我们努力构思X-PDT的相关药物中，我们设计了含有碘内配体的八面体钼簇复合物（MO_6），以及携带环氧乙烷有机功能的羧基化顶谱配体。该络合物的钠盐在水性介质中高度可溶于水性介质，并显示通过氧气有效淬灭的红色发光，以在高量子产率下产生O_2（〜1Δ_g）。此外，由于其高射线，复合物在水性介质中表现出辐射发光，具有与光致发光相同的光谱特征，表明在X射线照射时产生O_2（〜1Δ_g）。在孵育的第一小时内，HEP-2和MRC-5细胞的复合物的摄取可忽略不计，然后与顶端配体的水解有显着增加。该复合物在体外表现出低毒性，并诱导抗毒性毒性效果，鉴于癌症HEP-2细胞，但对正常的MRC-5细胞差别不计，X射线剂量不影响细胞活力。在小鼠模型上对MO_6复合物的体内毒性的第一次评价证明了对肾脏的中度和延迟毒性影响，静脉注射LD_（50）值390±30mg kg〜（-1），可能与水解相连 - 诱导复合物的聚集。总的来说，这种复杂的表现出具有X-PDT的单线氧放射剂的有吸引力的特征，突出了过渡金属簇复合物对这种方式的潜力。

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  • 来源
    《Biomaterials Science》 |2021年第8期|共10页
  • 作者

    Kaplan Kirakci; Tatiana N. Pozmogova; Andrey Y. Protasevich; Georgy D. Vavilov; Dmitri V. Stass; Michael A. Shestopalov; Kamil Lang;

  • 作者单位

    Institute of Inorganic Chemistry of the Czech Academy of Sciences Rez 1001 250 68 Husinec-Rez Czech Republic;

    SPF-vivarium Institute of Cytology and Genetics SB RAS 10 Acad. Lavrentieva ave. 630090 Novosibirsk Russia;

    Nikolaev Institute of Inorganic Chemistry SB RAS RAS 3 Acad. Lavrentiev ave. 630090 Novosibirsk Russia;

    National Medical Research Center for Circulation Pathology n.a. academician E.N. Meshalkin 15 Rechkunovskaya st. 630055 Novosibirsk Russia;

    Novosibirsk State University 1 Pirogova st. 630090 Novosibirsk Russia;

    Nikolaev Institute of Inorganic Chemistry SB RAS RAS 3 Acad. Lavrentiev ave. 630090 Novosibirsk Russia;

    Institute of Inorganic Chemistry of the Czech Academy of Sciences Rez 1001 250 68 Husinec-Rez Czech Republic;

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  • 正文语种 eng
  • 中图分类 计量学;
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