Polymeric photosensitizer-embedded self-expanding metal stent for repeatable endoscopic photodynamic therapy of cholangiocarcinoma
Polymeric photosensitizer-embedded self-expanding metal stent for repeatable endoscopic photodynamic therapy of cholangiocarcinoma
复制标题
DOI：
10.1016/j.biomaterials.2014.07.001
复制
发表时间：
2014-10-01
期刊：
影响因子：
14
通讯作者：
Reddy, D. Nageshwar
中科院分区：
文献类型：
--
作者：
Bae, Byoung-chan;Yang, Su-Geun;Reddy, D. Nageshwar
光动力学疗法（PDT）是姑息性治疗恶性胆管梗阻的一种新的治疗方法。在这项研究中，我们设计了光敏剂嵌入的自膨胀非血管金属支架（PDT支架），它允许可重复的光动力治疗胆管癌，而无需全身注射光敏剂。将高分子光敏剂（普鲁兰多糖醋酸酯结合脱镁叶绿酸A; PPA）掺入自膨式非血管金属支架中。在缓冲溶液中和小鼠皮下植入中估计PPA在支架中的驻留。通过激光照射载支架的肿瘤细胞株、HCT-116肿瘤-异种移植瘤小鼠模型和内镜下PDT支架介入小型猪胆管，评价PDT支架的光动力学活性。PDT-支架的光荧光成像显示聚合物Pheo-A（PPA）均匀包埋在支架膜上。PDT支架的光动力学活性至少维持2个月。这意味着支架置入后可重复内镜PDT。光暴露后的PDT支架成功地在周围组织中产生细胞毒性单线态氧，诱导肿瘤细胞的凋亡降解和小鼠模型上异种移植肿瘤的消退。对小型猪的内镜胆道支架内光动力治疗也表明PDT支架对胆管癌的潜在疗效。体内和体外研究表明，我们的PDT支架，允许可重复的内镜胆道PDT，有潜力的联合治疗（支架加PDT）的胆管癌。(C)2014爱思唯尔有限公司版权所有。
Photodynamic therapy (PDT) is a new therapeutic approach for the palliative treatment of malignant bile duct obstruction. In this study, we designed photosensitizer-embedded self-expanding nonvascular metal stent (PDT-stent) which allows repeatable photodynamic treatment of cholangiocarcinoma without systemic injection of photosensitizer. Polymeric photosensitizer (pullulan acetate-conjugated pheophorbide A; PPA) was incorporated in self-expanding nonvascular metal stent. Residence of PPA in the stent was estimated in buffer solution and subcutaneous implantation on mouse. Photodynamic activity of PDT-stent was evaluated through laserexposure on stent-layered tumor cell lines, HCT-116 tumor-xenograft mouse models and endoscopic intervention of PDT-stent on bile duct of mini pigs. Photo-fluorescence imaging of the PDT-stent demonstrated homogeneous embedding of polymeric Pheo-A (PPA) on stent membrane. PDT-stent sustained its photodynamic activities at least for 2 month. And which implies repeatable endoscopic PDT is possible after stent emplacement. The PDT-stent after light exposure successfully generated cytotoxic singlet oxygen in the surrounding tissues, inducing apoptotic degradation of tumor cells and regression of xenograft tumors on mouse models. Endoscopic biliary in-stent photodynamic treatments on minipigs also suggested the potential efficacy of PDT-stent on cholangiocarcinoma. In vivo and in vitro studies revealed our PDT-stent, allows repeatable endoscopic biliary PDT, has the potential for the combination therapy (stent plus PDT) of cholangiocarcinoma. (C) 2014 Elsevier Ltd. All rights reserved.