Department of Biology, University of Padova, 35131 Padova, Italy.
Eur J Cancer. 2010 Jul;46(10):1910-8. doi: 10.1016/j.ejca.2010.02.037. Epub 2010 Mar 29.
The efficiency of a Zn(II)-phthalocyanine disulphide (C11Pc), a compound with both phthalocyanine units bearing seven hexyl chains and a sulphur terminated C11 chain, as a photodynamic therapy (PDT) agent was investigated in C57 mice bearing a sub-cutaneously transplanted amelanotic melanoma. The phthalocyanine was intravenously injected at a dose of 1.5 micromol/kg body weight either free or bound to gold nanoparticles, using a Cremophor emulsion as a delivery vehicle. Biodistribution studies at selected post-injection times showed that the nanoparticle-associated C11Pc was recovered in significantly larger amounts from all the examined tissues and the serum and yielded a greater selectivity of tumour targeting: thus, the ratio between the amount of phthalocyanine recovered from the amelanotic melanoma and the skin (peritumoural tissue) increased from 2.3 to 5.5 from the free to the gold nanoparticle-bound C11Pc at 24 h after injection. PDT studies with the C11Pc-loaded amelanotic melanoma showed a markedly more significant response of the tumour in the mice that had received the nanoparticle-bound photosensitiser; the PDT effect was especially extensive if the irradiation was performed at 3h after C11Pc injection when large phthalocyanine amounts were still present in the serum. This suggests that the PDT promoted by C11Pc predominantly acts via vascular damage at least in this specific animal model. This hypothesis was fully confirmed by electron microscopy observations of tumour specimens obtained at different times after the end of PDT, showing an extensive damage of the blood capillaries and the endothelial cells.
具有七个己基链和硫端 C11 链的锌(II)-酞菁二硫化物 (C11Pc) 作为一种光动力疗法 (PDT) 剂在皮下移植无黑色素瘤的 C57 小鼠中的效率进行了研究。酞菁以 1.5 微摩尔/千克体重的剂量静脉注射，无论是游离的还是结合到金纳米粒子上，使用 Cremophor 乳液作为递送载体。在选定的注射后时间进行的生物分布研究表明，从所有检查的组织和血清中以明显更大的量回收与纳米粒子相关的 C11Pc，并产生了更大的肿瘤靶向选择性：因此，从无黑色素瘤中回收的酞菁量与皮肤（肿瘤周围组织）之间的比率从游离的 C11Pc 增加到注射后 24 小时的金纳米粒子结合的 C11Pc 的 5.5 倍。用载有 C11Pc 的无黑色素瘤进行的 PDT 研究表明，接受纳米粒子结合的光敏剂的小鼠中的肿瘤反应明显更为显著；如果在 C11Pc 注射后 3 小时进行照射，则 PDT 效果特别广泛，此时血清中仍存在大量酞菁。这表明 C11Pc 促进的 PDT 主要至少在这种特定的动物模型中通过血管损伤起作用。这一假设通过在 PDT 结束后不同时间获得的肿瘤标本的电子显微镜观察得到了充分证实，显示出毛细血管和内皮细胞的广泛损伤。
