Comparative in vitro study on the characteristics of different photosensitizers employed in PDT
Comparative in vitro study on the characteristics of different photosensitizers employed in PDT
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DOI：
10.1016/j.jphotobiol.2010.06.004
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发表时间：
2010-09-02
影响因子：
5.4
通讯作者：
Plaetzer, Kristjan
中科院分区：
文献类型：
--
作者：
Berlanda, Juergen;Kiesslich, Tobias;Plaetzer, Kristjan
目前，光动力疗法（PDT）中使用的光敏剂种类繁多，且具有非常不同的特性。虽然，无数的体外研究的属性的光敏剂确实存在，这些物质在一个细胞系的直接比较是罕见的，可能有助于选择最佳的光敏物质的特定应用。因此，我们评估了六种广泛使用的光敏剂，即Foscan（R）、Fospeg（R）、金丝桃素、四磺酸酞菁铝（III）氯化物（AlPcS 4）、5-氨基乙酰丙酸（ALA）和Photofrin（R）的性质：（i）无光照的细胞毒性，（ii）光毒性，（iii）细胞摄取和释放，和（iv）使用可比较的照射方案在A431人表皮样癌细胞中诱导凋亡。我们清楚地表明，内消旋-四羟基苯基二氢卟酚（mTHPC，Foscan（R））是一种非常有效的光敏剂，其在非常低的浓度下诱导高的光毒性。对于mTHPC的水溶性制剂Fospeg（R），观察到类似的体外特征和光毒性。金丝桃素是一种从金丝桃属植物中提取的光敏剂，在很宽的光通量范围内都能有效诱导细胞凋亡。AlPcS 4吸收674 nm波长的光，在组织中提供更高的穿透深度。其亲水特性允许作为水溶液应用。ALA可以在黑暗中以非常高的浓度施用而不产生细胞毒性作用。原卟啉IX的细胞内浓度迅速下降后撤销ALA，从而最大限度地减少PDT后的光敏感期。在所有光敏剂中，Photofrin（R）获得了大多数临床批准，并作为标准。(C)2010爱思唯尔有限公司版权所有。
At present a wide range of photosensitizers are employed in photodynamic therapy (PDT) that have very different characteristics. Although, countless in vitro studies on the attributes of photosensitizers do exist, a direct comparison of these substances on one cell line are rare and may contribute to the choice of the optimal photoactive substance for a specific application. We therefore evaluated the properties of six widespread photosensitizers, namely Foscan (R), Fospeg (R), hypericin, aluminum (III) phthalocyanine tetrasulfonate chloride (AlPcS4), 5-aminolevulinic acid (ALA), and Photofrin (R) in terms of: (i) cytotoxicity without illumination, (ii) phototoxicity, (iii) cellular uptake and release, and (iv) apoptosis induction in A431 human epidermoid carcinoma cells using comparable illumination regimens. We clearly show that meso-tetrahydroxyphenylchlorin (mTHPC, Foscan (R)) is a very effective photosensitizer inducing high phototoxicity at very low concentrations. Similar in vitro characteristics and phototoxicity were observed for Fospeg (R), the water-soluble formulation of mTHPC. Hypericin, a photosensitizer extracted from plants of the Hypericum genus, is very effective in inducing apoptosis over a wide range of light fluences. AlPcS4 absorbs light of 674 nm wavelength providing a higher penetration depth in tissue. Its hydrophilic character allows for application as aqueous solution. ALA can be administered at very high concentrations without producing cytotoxic effects in the dark. The intracellular concentration of protoporphyrin IX rapidly decreases after withdrawal of ALA, thus minimizing the period of light sensitivity post PDT. Among all photosensitizers Photofrin (R) has most clinical approvals and serves as standard. (C) 2010 Elsevier B.V. All rights reserved.