Photodynamic therapy of intimal hyperplasia : Selective destruction by scavenger receptor mediated mechanism

我们之前已经表明，马来酰化牛血清白蛋白（mal-BSA）与光敏剂氯e6结合，在内膜增生（IH）的内侧定位较高，并有效地作为PDT的光敏剂。PDT作为一种清除剂给药系统治疗IH在大鼠动脉壁损伤模型中显示出有效的效果。在这项研究中，我们测试了使用第二代光敏剂单l -天冬氨酸氯e6 （NPe6）的圆柱形纤维在气球损伤动脉中的放射照射效果。采用兔腹腔和髂动脉（球囊损伤）模型评价NPe6的摄取。球囊损伤时注射NPe6 （5mg/kg）。注射后3小时，取损伤和未损伤主动脉（对照组），荧光显微镜检查。球囊损伤动脉在介质中的荧光分布明显高于非损伤动脉。用二极管激光器进行激光照射，发射波长为664 nm。PDT后4天和2周，切除动脉并进行组织学检查。结果表明，在第4天桡骨上观察到无细胞动脉壁。在2周和4周时，周围的纤维血管组织和组织细胞向内生长受到限制，无法渗透到非细胞介质中，新内膜的形成受到抑制。在该动脉壁损伤模型中，用664nm光照射NPe6致敏的损伤动脉，可以有效地限制内膜增生的形成。未来的研究将利用血管内技术在体内探索mal-BSA光敏剂偶联物的效率，以开发临床上有用的内膜增生治疗方法。

We have previously shown that maleylated-bovine serum albumin (mal-BSA) conjugated with a photosensitizer, chlorin e6, localizes higher in inner side of intimal hyperplasia (IH) and functions effectively as a photosensitizer for PDT. PDT as a treatment of IH using this scavenger-medicated delivery system shows effective in rat model of arterial wall injury. In this study, we tested the effect of a cylindrical fiber for intra-arterial radial irradiation using a second generation photosensitizer, mono-L-aspartyl chlorin e6 (NPe6) in baloon injured arteries. A rabbit model was used to evaluate NPe6 uptake in abdominal and iliac (balloon injured) arteries. NPe6 was injected at the time of balloon injuries (5mg/kg). Three hours following injection, injured and non injured aorta (control) were retrieved and examined by fluorescence microscopy. Balloon injured arteries showed significantly higher fluorescence distribution in the media compared to non injured arteries. Laser irradiations were performed with a diode laser to emit 664 nm. Four days and 2 weeks after PDT, the arteries were excised and examined histologically. The results indicated that accellular arterial walls by cell depletion were observed radially at four days. Surrounding fibrovascular tissure and histiocytes ingrowth were limitted to penetrate to the acellular media and neointimal formation was suppressed at two and four weeks. Treatment of NPe6 sensitized, injured arteries with 664nm of light irradiation intraluminally is effective in limiting formation of intimal hyperplasia in this model of arterial wall injury. Future studies will explore the efficiency of mal-BSA photosensitizer conjugates using endovascular technique in vivo to develop clinically useful treatment for intimal hyperplasia.