Tumour-localizing and -photo sensitising properties of meso-tetra(4-nido-carboranylphenyl)porphyrin (H2TCP)
Tumour-localizing and -photo sensitising properties of meso-tetra(4-nido-carboranylphenyl)porphyrin (H2TCP)
复制标题
DOI：
10.1016/j.jphotobiol.2007.09.012
复制
发表时间：
2007-12-14
影响因子：
5.4
通讯作者：
Soncin, Marina
中科院分区：
文献类型：
--
作者：
Fabris, Clara;Vicente, M. Graca H.;Soncin, Marina
一种含36个硼原子的水溶性中位取代卟啉（H2TCP）是一种高效的光动力敏化剂（单线态氧量子产率=0.44），研究了其在小鼠黑色素瘤细胞中的积累（B16F1）。细胞中H2TCP的含量随卟啉浓度的增加而增加，且至少达到100 μ M，但在黑暗中没有明显的细胞毒性作用。H2TCP的摄取随着孵育时间的增加而增加，达到一个平台值，对应于孵育24 h后每mg细胞蛋白中H2TCP的回收率为0.4 nmol。荧光显微镜观察显示，卟啉主要定位于细胞内，在细胞质中呈现离散分布，其模式与内体探针路西弗黄的观察结果非常相似。研究H2TCP对B16F1细胞不同照射次数（1 ~ 15 min）和孵育次数（1 ~ 24 h）的光敏效果。用20 μ M H2TCP孵育，用红光（600-700 nm, 20 mW/cm(2)）照射10 min，细胞几乎完全（bb0 95%）死亡。静脉注射到皮下移植黑色素瘤的C57BL/6小鼠后，卟啉也在肿瘤组织中积累了可观的量。将H2TCP溶解在20%二甲基亚砜(DMSO)-30%聚乙二醇(peg400)-50%水的三元混合物中，可以最大限度地积累道管。因此，这种卟啉既可以作为光动力治疗剂，也可以作为硼中子俘获治疗的放射增敏剂。(c) 2007 Elsevier B.V.版权所有
A water-soluble meso-substituted porphyrin (H2TCP) bearing 36 boron atoms, which appeared to be an efficient photodynamic sensitiser (singlet oxygen quantum yield=0.44), was studied for its accumulation by murine melanotic melanoma cells (B16F1). The amount of H2TCP in the cells increased with the porphyrin dose in the incubation medium up to, and at least, 100 mu M concentrations with no significant cytotoxic effect in the dark. Moreover, the H2TCP uptake increased with the incubation time reaching a plateau value corresponding with the recovery of 0.4 nmol of H2TCP per mg of cell proteins after 24 h incubation. Fluorescence microscopy observations showed that the porphyrin was largely localized intracellularly, exhibiting a discrete distribution in the cytoplasm with a pattern which was closely similar to that observed for the endosomal probe Lucifer yellow. The photosensitising efficiency of the H2TCP toward B16F1 cells was studied for different irradiation (1-15 min) and incubation (1-24 h) times. Nearly complete (> 95%) cell mortality was obtained upon incubation with 20 mu M H2TCP and 10 min irradiation with red light (600-700 nm, 20 mW/cm(2)). The porphyrin was also accumulated in appreciable amounts by the tumour tissue after intravenous injection to C57BL/6 mice bearing a subcutaneously transplanted melanotic melanoma. Maximum accumulation in the turnout was achieved by administration of H2TCP dissolved in the ternary mixture 20% dimethylsulfoxide (DMSO)-30% polyethyleneglycol (PEG 400)-50% water. Thus, this porphyrin could act as both a photodynamic therapy agent and a radiosensitising agent for boron neutron capture therapy. (c) 2007 Elsevier B.V. All rights reserved.