The PDT activity of free and pegylated pheophorbide a against an amelanotic melanoma transplanted in C57/BL6 mice
The PDT activity of free and pegylated pheophorbide a against an amelanotic melanoma transplanted in C57/BL6 mice
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DOI：
10.1007/s10637-012-9844-4
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发表时间：
2013-02-01
影响因子：
3.4
通讯作者：
Xodo, Luigi E.
中科院分区：
文献类型：
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作者：
Rapozzi, Valentina;Zorzet, Sonia;Xodo, Luigi E.
脱镁叶绿酸a（Pheophorbide a，Pba）是一种叶绿素分解代谢产物，已被提出作为光动力学治疗中的光敏剂。在先前的研究中，我们将Pba与单甲氧基聚乙二醇（mPEG-Pba）缀合，以增加其溶解度和药代动力学。在这里，我们比较了游离Pba和mPEG-Pba的光动力疗法治疗C57/BL 6小鼠移植的皮下无黑色素性黑色素瘤的疗效。腹腔注射光敏剂（30 mg/kg），当动物保持在黑暗中时，没有显示出毒性。但是，在用660 nm激光（能量密度为193 J/cm（2））光活化后，两种光敏剂，特别是mPEG-Pba，在肿瘤生长延迟和Kaplan-Meier中位生存时间增加方面都显示出治愈肿瘤的强大功效。总之，我们的体内数据表明，mPEG缀合的Pba是一种有前途的光敏剂，用于癌症的光动力治疗。
Pheophorbide a (Pba) is a chlorophyll catabolite that has been proposed as photosensitizer in photodynamic therapy. In a previous study we conjugated Pba to monomethoxy-polyethylene glycol (mPEG-Pba), to increase its solubility and pharmacokinetics. Here, we compare the photodynamic therapy efficacy of free Pba and mPEG-Pba to cure a subcutaneous amelanotic melanoma transplanted in C57/BL6 mice. The photosensitizers, i.p. injected (30 mg/kg), showed no toxicity when the animals were kept in the dark. But, after photoactivation with a 660 nm laser (fluence of 193 J/cm(2)), both photosensitizers, in particular mPEG-Pba, showed a strong efficacy to cure the tumor, both in terms of tumor growth delay and increase of Kaplan-Meier median survival time. Together, our in vivo data demonstrate that mPEG-conjugated Pba is a promising photosensitizer for the photodynamic therapy of cancer.