Allison B A, Crespo M T, Jain A K, Richter A M, Hsiang Y N, Levy J G
Department of Surgery, University of British Columbia, Vancouver, Canada.
Photochem Photobiol. 1997 May;65(5):877-83. doi: 10.1111/j.1751-1097.1997.tb01938.x.
In this study we compared the plasma distribution and arterial accumulation of a photosensitizer, benzoporphyrin derivative (BPD), in two models of atherosclerosis: the spontaneous lesions of the Watanabe heritable hyperlipidemic (WHHL) rabbit and induced lesions of the balloon-injured, cholesterol-fed New Zealand white (NZW) rabbit. Selective uptake and retention of a photosensitizer by the abnormal portion of a vessel is a necessity in order for photodynamic therapy to become a successful modality for inhibition of intimal hyperplasia, selective removal of atherosclerotic tissue or imaging of diseased arteries. Liposome-based formulations were compared to freshly isolated native low density lipoprotein (LDL) and acetylated-LDL (Ac-LDL) as delivery vehicles for BPD. Plasma distribution of the photosensitizer was analyzed by KBr density gradient ultracentrifugation. Although the delivery vehicle influenced plasma distribution immediately postinjection, BPD subsequently partitioned according to the plasma concentration of the lipoproteins. Photosensitizer level in plaque and normal artery specimens was determined by ethyl acetate extraction and spectrofluorometric measurement. The measurement of BPD in normal and atherosclerotic arterial tissue demonstrated a selective accumulation in atherosclerotic tissue. Preassociation with LDL and Ac-LDL enhanced accumulation of BPD in atherosclerotic tissue when compared with normal artery (mean ratios of 2.8 and 4.1 were achieved, respectively). These results indicate that the preferential uptake of BPD by atherosclerotic plaque can be enhanced by preassociation with plasma lipoproteins, suggesting that light activation could lead to a highly selective destruction of diseased vascular tissue.
在本研究中，我们比较了一种光敏剂苯并卟啉衍生物（BPD）在两种动脉粥样硬化模型中的血浆分布和动脉蓄积情况：渡边遗传性高脂血症（WHHL）兔的自发性病变以及球囊损伤并喂食胆固醇的新西兰白兔（NZW）的诱导性病变。为了使光动力疗法成为抑制内膜增生、选择性清除动脉粥样硬化组织或对病变动脉进行成像的成功方法，血管异常部分对光敏剂的选择性摄取和保留是必要的。将基于脂质体的制剂与新鲜分离的天然低密度脂蛋白（LDL）和乙酰化LDL（Ac-LDL）作为BPD的递送载体进行了比较。通过KBr密度梯度超速离心分析光敏剂的血浆分布。尽管递送载体在注射后立即影响血浆分布，但BPD随后根据脂蛋白的血浆浓度进行分配。通过乙酸乙酯萃取和荧光分光光度法测定斑块和正常动脉标本中的光敏剂水平。在正常和动脉粥样硬化动脉组织中对BPD的测量表明，其在动脉粥样硬化组织中有选择性蓄积。与正常动脉相比，与LDL和Ac-LDL预结合可增强BPD在动脉粥样硬化组织中的蓄积（分别达到2.8和4.1的平均比值）。这些结果表明，与血浆脂蛋白预结合可增强动脉粥样硬化斑块对BPD的优先摄取，这表明光激活可能导致对病变血管组织的高度选择性破坏。
