经皮穿刺光纤导入瘤内光动力疗法治疗肺癌的基础与临床研究

The incidence of tumor is increase year by year, one of the top three causes of death in individual countries, it is great harm to human health. At present, the main treatments of cancer is radiotherapy, chemotherapy and surgical resection and so on, but they have greatly side effects and poor efficacy. Photodynamic therapy (PDT) is a minimally invasive treatment, which developed on the basis of laser therapy, it can induce apoptosis and necrosis. The technique have many advantages, such as selective, effective, reproducible, flexible, minimally invasive and practical and so on. This project is to design the basis and clinical research of photodynamic therapy for tumor. Firstly, we establish animal model with a tumor, the site of photosensitizer aggregates in tumor tissue can be determined by a live imager, then application the method that transdermal fibers are introduced into the tumor tissue to treatment of PDT, at the same time, comparing and optimizing for the illumination time, photosensitizer injection mode and dosage to observing and exploring efficacy; then the reliable data obtaining from basic research apply to clinical, for such patients with lung cancer who are not suitable for surgical treatment or site difficult tumors, we carry out PDT treatment through this method that transdermal fibers are introduced into the tumor tissue in CT-guided, thus can reduce the suffering, treatment costs and increase the targeted therapy for patients.

肿瘤发病率逐年增高，是各国人口中前三位的死因之一，极大的危害着人类健康。目前，对肿瘤的治疗主要有放疗、化疗及手术切除等方法，但副作用大、疗效差。光动力疗法(Photodynamic therapy PDT)是在激光治疗学基础上发展起来的一种能诱导细胞凋亡和坏死的微创性治疗手段。该技术具有选择性、有效性、可重复性、灵活性、微创性、实用性等优点。本项目拟设计经皮穿刺光纤导入瘤内光动力疗法治疗肺癌的基础与临床研究。首先建立动物模型，利用活体成像仪定位光敏剂聚集的肿瘤部位，应用经皮穿刺光纤导入肺癌组织内的方法进行PDT，并对光照时间、光敏剂注射方式及剂量等进行对比优化，探究其疗效；然后将基础研究得到的数据应用于临床，对不宜接受手术治疗的局限性肿瘤，或由于肿瘤生长部位而难以进行手术治疗的肺癌患者在CT引导下经皮穿刺光纤导入肿瘤部位进行PDT，以减轻患者的痛苦和治疗成本，增加治疗的靶向性。

光动力疗法通过破坏肿瘤细胞的结构或者影响细胞的功能，诱导细胞发生凋亡和坏死，从而达到治疗的效果，它同时具有微创性、靶向准确、不良反应少、可重复治疗、易恢复等优势；所以这一新型的治疗方法正引起人们的广泛关注和研究。本项目构建了皮下接种肺癌A549细胞的动物模型，通过经皮穿刺光纤导入瘤内的光动力疗法，将动物分为模型组、激光组、光动力治疗组，其中光动力治疗组根据药物剂量分为低剂量、中剂量、高剂量组，探究光动力治疗的最佳药物剂量以及光照时间，实验结果表明，光动力疗法可以通过下调瘤体组织中 VEGF和b-FGF的表达水平，抑制新生血管的形成，阻断肿瘤组织获得丰富的营养物质的通道，进而起到治疗的效果。光动力疗法可以提高裸鼠的抑瘤率，且从光镜下观察瘤体的形态变化发现随着光敏剂药物浓度的增加，坏死程度增加，说明光动力疗法对肿瘤有很好的治疗效果。实验制备的纳米光敏剂Lip@Ce6相比于普通光敏剂Ce6，可有效增强了PDT治疗肺癌的疗效，当Lip@Ce6-PDT的浓度为10mg/kg时，抑瘤率为53.9%，实现了药物递送与治疗。当采用薄膜蒸发法成功制备了PTX&Ce6-LP，光动力与化疗联合能够有效地抑制肿瘤的生长，实现完全清除，4次治疗后3.75mg/kg组的抑瘤率62.3%，Bax的表达增强，Bcl-2的表达减弱。以上一系列实验为肺癌的临床治疗提供了一种新的思路，也为临床PDT治疗寻找最佳光敏剂剂量的量效研究提供了一定的参考价值。