A novel approach to a bifunctional photosensitizer for tumor imaging and phototherapy
A novel approach to a bifunctional photosensitizer for tumor imaging and phototherapy
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DOI：
10.1021/bc050177o
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发表时间：
2005-09-01
影响因子：
4.7
通讯作者：
Pandey, RK
中科院分区：
文献类型：
--
作者：
Chen, YH;Gryshuk, A;Pandey, RK
光学成像在分子识别研究中引起了极大的关注，因为用现有的实验室仪器可以在均质和非均质介质中检测到微小的荧光示踪剂。在我们的初步研究中，一种临床相关的光敏剂（HPPH，一种叶绿素-a类似物）与一种花青素染料连接（具有所需的光物理特性，但肿瘤选择性有限），并发现所得到的偶联物是一种有效的肿瘤成像（荧光成像）和光敏剂。与HPPH相比，在共轭物中存在的花青素染料片段在肿瘤中产生的摄取明显高于皮肤。在治疗/成像剂量下，缀合物没有表现出任何明显的皮肤光毒性，这是大多数卟啉基光敏剂的主要缺点。这些结果表明，基于肿瘤的卟啉化合物可以作为“载体”，将所需的荧光剂输送到肿瘤中。肿瘤成像或改进的光动力治疗剂的发展本身是重要的一步，但双功能剂（荧光成像和光动力治疗）为肿瘤检测和靶向光动力治疗提供了潜力，将两种模式结合成一种具有成本效益的“观察和治疗”方法。
Optical imaging has attracted a great attention for studying molecular recognitions because minute fluorescent tracers can be detected in homogeneous and heterogeneous media with existing laboratory instruments. In our preliminary study, a clinically relevant photosensitizer (HPPH, a chlorophyll-a analog) was linked with a cyanine dye (with required photophysical characteristics but limited tumor selectivity), and the resulting conjugate was found to be an efficient tumor imaging (fluorescence imaging) and photosensitizing agent. Compared to HPPH, the presence of the cyanine dye moiety in the conjugate produced a significantly higher uptake in tumor than skin. At a therapeutic/imaging dose, the conjugate did not show any significant skin phototoxicity, a major drawback associated with most of the porphyrin-based photosensitizers. These results suggest that tumor-avid porphyrin-based compounds can be used as "vehicles" to deliver the desired fluorescent agent(s) to tumor. The development of tumor imaging or improved photodynamic therapy agent(s) by itself represents an important step, but a dual function agent (fluorescence imaging and photodynamic therapy) provides the potential for tumor detection and targeted photodynamic therapy, combining two modalities into a single cost-effective "see and treat" approach.