X-Ray Induced Photodynamic Therapy: A Combination of Radiotherapy and Photodynamic Therapy.

X-Ray Induced Photodynamic Therapy: A Combination of Radiotherapy and Photodynamic Therapy.
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DOI:
10.7150/thno.16141
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发表时间:
2016
期刊:
影响因子:
12.4
通讯作者:
Xie J
Xie J
中科院分区:
医学1区
文献类型:
--
作者:
Wang GD;Nguyen HT;Chen H;Cox PB;Wang L;Nagata K;Hao Z;Wang A;Li Z;Xie J

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传统光动力疗法(PDT)的临床应用受到光穿透深度的限制。为了解决这个问题,我们最近开发了 X 射线诱导光动力疗法 (X-PDT),它利用 X 射线作为能量来源来激活 PDT 过程。除了打破浅组织穿透法则之外,我们的研究还发现,X-PDT 比单独放疗 (RT) 更有效地杀死肿瘤细胞。然而,细胞毒性背后的机制尚未阐明。在本研究中,我们研究了 X-PDT 对癌细胞的作用机制。我们的结果表明,X-PDT 不仅仅是 PDT 衍生物,而且本质上是 PDT 和 RT 的组合。这两种疗法针对不同的细胞成分(分别是细胞膜和 DNA),从而增强治疗效果。因此,X-PDT 不仅降低了癌细胞的短期活力,而且从长远来看也降低了它们的克隆性。从这个角度来看,X-PDT也可以被视为一种独特的放射增敏方法,因此它在肿瘤治疗中比RT具有明显的优势,特别是对于放射抗性细胞。这不仅在体外得到了证实,而且在皮下接种或植入小鼠肺部的 H1299 肿瘤体内也得到了证实。这些发现和进展对于 X-PDT 作为一种新型癌症治疗方式的发展具有重要意义。
Conventional photodynamic therapy (PDT)'s clinical application is limited by depth of penetration by light. To address the issue, we have recently developed X-ray induced photodynamic therapy (X-PDT) which utilizes X-ray as an energy source to activate a PDT process. In addition to breaking the shallow tissue penetration dogma, our studies found more efficient tumor cell killing with X-PDT than with radiotherapy (RT) alone. The mechanisms behind the cytotoxicity, however, have not been elucidated. In the present study, we investigate the mechanisms of action of X-PDT on cancer cells. Our results demonstrate that X-PDT is more than just a PDT derivative but is essentially a PDT and RT combination. The two modalities target different cellular components (cell membrane and DNA, respectively), leading to enhanced therapy effects. As a result, X-PDT not only reduces short-term viability of cancer cells but also their clonogenecity in the long-run. From this perspective, X-PDT can also be viewed as a unique radiosensitizing method, and as such it affords clear advantages over RT in tumor therapy, especially for radioresistant cells. This is demonstrated not only in vitro but also in vivo with H1299 tumors that were either subcutaneously inoculated or implanted into the lung of mice. These findings and advances are of great importance to the developments of X-PDT as a novel treatment modality against cancer.
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影响因子: 5.4
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