Sonodynamic therapy of cancer using a novel porphyrin derivative, DCPH-P-Na(I), which is devoid of photosensitivity
Sonodynamic therapy of cancer using a novel porphyrin derivative, DCPH-P-Na(I), which is devoid of photosensitivity
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DOI：
10.1111/j.1349-7006.2007.00468.x
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发表时间：
2007-06-01
期刊：
影响因子：
5.7
通讯作者：
Kuroki, Masahide
中科院分区：
文献类型：
--
作者：
Hachimine, Ken;Shibaguchi, Hirotomo;Kuroki, Masahide
为了提高光敏剂声动力学治疗肿瘤的效果，我们开发了一种新的卟啉衍生物DCPH-P-Na（I），并研究了其光化学特性和对肿瘤细胞的声毒性。DCPH-P-Na（I）在光激发下显示出最小的荧光发射，而ATX-70的发射很强，已知ATX-70显示出光毒性和声毒性。根据这一观察结果，与ATX-70的强光毒性相反，在体外存在DCPH-P-Na（I）的情况下，将人肿瘤细胞暴露于光时，观察到的光毒性最小。然而，DCPH-P-Na（I）在体外超声照射下对肿瘤细胞表现出强烈的声毒性。加入L-组氨酸而不是D-甘露醇可降低这种声毒性，因此表明单线态氧可能是DCPH-P-Na（I）声毒性的原因。DCPH-P-Na（I）对来自不同组织的多种癌细胞系表现出显著的声毒性。此外，在小鼠异种移植模型中，在向小鼠施用DCPH-P-Na（I）后，使用超声处理观察到肿瘤的有效生长抑制。这些结果表明，DCPH-P-Na（I）的声动力疗法因此可能是用于位于人体深处的癌症的有用的临床治疗，而不诱导皮肤敏感性，这往往是光敏剂的主要副作用。
To improve the efficacy of sonodynamic therapy of cancer using photosensitizers, we developed a novel porphyrin derivative designated DCPH-P-Na(I) and investigated its photochemical characteristics and sonotoxicity on tumor cells. DCPH-P-Na(I) exhibited a minimum fluorescent emission by excitation with light, compared with a strong emission from ATX-70, which is known to reveal both photo- and sonotoxicity. According to this observation, when human tumor cells were exposed to light in the presence of DCPH-P-Na(I) in vitro, the least phototoxicity was observed, in contrast to the strong phototoxicity of ATX-70. However, DCPH-P-Na(I) exhibited a potent sonotoxicity on tumor cells by irradiation with ultrasound in vitro. This sonotoxicity was reduced by the addition of L-histidine, but not D-mannitol, thus suggesting that singlet oxygen may be responsible for the sonotoxicity of DCPH-P-Na(I). DCPH-P-Na(I) demonstrated significant sonotoxicity against a variety of cancer cell lines derived from different tissues. In addition, in a mouse xenograft model, a potent growth inhibition of the tumor was observed using sonication after the administration of DCPH-P-Na(I) to the mouse. These results suggest that sonodynamic therapy with DCPH-P-Na(I) may therefore be a useful clinical treatment for cancers located deep in the human body without inducing skin sensitivity, which tends to be a major side-effect of photosensitizers.