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RGD-modified dihydrolipoamide dehydrogenase conjugated to titanium dioxide nanoparticles - switchable integrin-targeted photodynamic treatment of melanoma cells

机译:RGD改性二氢酚酰胺脱氢酶与二氧化钛纳米颗粒 - 可切换整合素靶向光动力学治疗黑素瘤细胞

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摘要

The photocytotoxic effect of UVA-excited titanium dioxide (TiO2), which is caused by the generation of reactive oxygen species (ROS), is often used in medical applications, such as cancer treatment. Photodynamic-therapy (PDT) is applied in several cancer models including cutaneous melanoma (CM), however the lack of selectivity causing damage to surrounding healthy tissues limits its applicability and novel targeted-delivery approaches are required. As cancer cells often overexpress integrin receptors (e.g. alpha v beta(3)) on their cell surface, targeted delivery of TiO2 nanoparticles (NPs) via an Arg-Gly-Asp (RGD) motif would make PDT more selective. We have recently reported that the mitochondria) enzyme dihydrolipoamide dehydrogenase (DLDH) strongly and specifically conjugates TiO2 via coordinative bonds. In this work we have modified DLDH with RGD moieties (DLDH RGD ), creating a molecular bridge between the integrin-expressing cancer cells and the photo-excitable TiO2 nanoparticles. Physicochemical assays have indicated that the hybrid-conjugated nanobiocomplex, TiO2-DLDHRGD, is producing controlled-release ROS under UVA illumination, with anatase NPs being the most photoreactive TiO2 form. This drug delivery system exhibited a cytotoxic effect in alpha v beta(3) integrin-expressing mice melanoma cells (B16F10), but not in normal cells lacking this integrin (HEK293). No cytotoxic effect was observed in the absence of UV illumination. Our results demonstrate the feasibility of combining the high efficiency of TiO2-based PDT, with an integrin-mediated tumor-targeted drug delivery for nanomedicine.
机译:由由反应性氧(ROS)产生的UVA激发二氧化钛(TiO 2)的光致毒性作用通常用于医疗应用,例如癌症治疗。光动力治疗(PDT)适用于包括皮肤黑素瘤(CM)的几种癌症模型,然而缺乏对周围健康组织损坏的选择性限制了其适用性,并且需要新的靶向递送方法。由于癌细胞通常过表达整联蛋白受体(例如,αvβ(3))在其细胞表面上,通过Arg-gly-Asp(RGD)基序的TiO 2纳米颗粒(NPS)的靶向递送将使PDT更具选择性。我们最近报道了线粒体)酶二氢酰胺脱氢酶(DLDH)通过协调键强,特别是缀合TiO 2。在这项工作中,我们已经改性RGD部分(DLDH RGD)DLDH,创建所述整合素表达的癌细胞和光激发的TiO 2纳米颗粒之间的分子桥。物理化学测定表明,杂化缀合的纳米飞物TiO2-DLDHRGD在UVA照明下产生控制释放ROS,锐钛矿NP是最光反应的TiO 2形式。该药物递送系统在αvβ(3)中表达表达蛋白的小鼠黑色素瘤细胞(B16F10)表现出细胞毒性作用,但不在缺乏该整合素的正常细胞中(HEK293)。在没有UV照明的情况下没有观察到细胞毒性效应。我们的结果表明,结合基于TiO2的PDT的高效率的可行性,具有整合蛋白介导的纳米疗程的肿瘤靶向药物递送。

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  • 来源
    《RSC Advances》 |2018年第17期|共8页
  • 作者单位

    George S Wise Fac Life Sci Sch Mol Cell Biol &

    Biotechnol Tel Aviv Israel;

    George S Wise Fac Life Sci Sch Mol Cell Biol &

    Biotechnol Tel Aviv Israel;

    Tel Aviv Univ Sackler Sch Med Dept Human Mol Genet &

    Biochem IL-69978 Ramat Aviv Israel;

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  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类 化学;
  • 关键词

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