The in vivo efficacy of phthalocyanine-nanoparticle conjugates for the photodynamic therapy of amelanotic melanoma
The in vivo efficacy of phthalocyanine-nanoparticle conjugates for the photodynamic therapy of amelanotic melanoma
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DOI：
10.1016/j.ejca.2010.02.037
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发表时间：
2010-07-01
影响因子：
8.4
通讯作者：
Russell, David A.
中科院分区：
文献类型：
--
作者：
Camerin, Monica;Magaraggia, Michela;Russell, David A.
用C57小鼠皮下移植无色素性黑色素瘤模型，研究了锌(II)-二硫化酞菁(C11Pc)作为光动力疗法(PDT)的疗效。以克莫弗乳剂为载体，以1.5微克摩尔/千克体重自由或结合金纳米颗粒为载体，静脉注射酞菁。在选定的注射后时间的生物分布研究表明，与纳米颗粒相关的C11Pc在所有受检组织和血清中的回收率显著增加，并产生了更高的肿瘤靶向性：因此，从无色素性黑色素瘤中回收的酞菁与皮肤(瘤周组织)之间的比率在注射后24小时从游离的C11Pc增加到与金纳米颗粒结合的C11Pc的比率从2.3增加到5.5。对负载C11Pc的无色素性黑色素瘤的PDT研究表明，在接受纳米颗粒结合光敏剂的小鼠中，肿瘤的反应明显更显著；如果在C11Pc注射后3小时进行照射，而血清中仍然存在大量的酞菁，则PDT效应尤其广泛。这表明，至少在这个特定的动物模型中，C11Pc促进的PDT主要通过血管损伤起作用。在PDT结束后不同时间获得的肿瘤标本的电子显微镜观察充分证实了这一假说，显示出毛细血管和内皮细胞的广泛损伤。(C)2010爱思唯尔有限公司。保留所有权利。
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 mu mol/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 3 h 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. (C) 2010 Elsevier Ltd. All rights reserved.