Assessment of the Cytotoxicity of the Photosensitizing Drug BPD Verteporfin Using Human Vascular Smooth Muscle Cells in Culture
Assessment of the Cytotoxicity of the Photosensitizing Drug BPD Verteporfin Using Human Vascular Smooth Muscle Cells in Culture
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使用培养的人血管平滑肌细胞评估光敏药物 BPD 维替泊芬的细胞毒性
DOI：
10.1097/00005344-199511000-00009
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发表时间：
1995
影响因子：
3
通讯作者：
M. Lowry
中科院分区：
文献类型：
--
作者：
R. Labow;L. Higginson;J. Irvine;M. Keaney;R. Masters;J. Marquis;E. Meek;T. Mussivand;V. Walley;P. Logan;N. Chaly;M. Lowry
光敏药物被富含脂质的病变选择性地吸收，如动脉粥样斑块，当暴露在光线下时，使药物具有细胞毒性。然而，持续数周的皮肤光敏性是一个显著的副作用。我们研究了一种新的光敏药物的细胞毒性，即苯并卟啉衍生物BPD维替波芬（Quadra Logic Technologies），它没有这种有害的副作用。从正常乳腺和病变冠状动脉中培养血管平滑肌细胞（VSMC），并对其生长速率进行了表征。通过测量治疗后的生存能力来评估有光和无光对BPD的敏感性。光致BPD 50%生存能力丧失（LD50）的致死剂量约为乳腺动脉12.5 ng/ml，细胞存活率为52 +/- 8% （n = 6）。尽管来自所有患者来源的冠状动脉VSMC的生长速度有显著差异，但在与乳腺动脉SMC相同浓度的BPD （p = NS）下，冠状动脉VSMC的存活率为44.6% /- 6% （n = 12）。我们的研究结果建立了用人动脉源SMC治疗BPD的LD50，并表明细胞的生长速度不影响药物的细胞毒性。
Photosensitizing drugs are selectively taken up by lipid-rich lesions such as atheromatous plaque which when exposed to light render the drugs cytotoxic. However, skin photosensitivity which persists for many weeks is a significant side effect. We investigated the cytotoxicity of a new photosensitizing drug, the benzoporphyrin derivative BPD verteporfin (Quadra Logic Technologies), which does not have this deleterious side effect. Vascular smooth muscle cells (VSMC) from normal human mammary and diseased human coronary arteries were grown in culture from explants and characterized with respect to their growth rates. The sensitivity to BPD with and without light was assessed by measuring viability after treatment. The lethal dose of drug for 50% viability loss (LD50) for BPD with light was approximately 12.5 ng/ml for mammary artery, with 52 +/- 8% cell survival (n = 6). The coronary artery VSMC from all patient sources, although differing significantly in growth rate, had a survival of 44 +/- 6% (n = 12) at the same concentration of BPD used for the mammary artery SMC (p = NS). Our results established the LD50 for BPD using human arterial sources of SMC and showed that the growth rates of the cells did not affect the cytotoxicity of the drug.