基于大麻素2型受体适配体的靶向多模态光敏剂的基础研究

项目名称： 基于大麻素2型受体适配体的靶向多模态光敏剂的基础研究

项目编号： No.81671739

项目类型： 面上项目

立项/批准年度： 2017

项目学科： 医药、卫生

项目作者： 贾宁阳

作者单位： 中国人民解放军第二军医大学

项目金额： 25万元

中文摘要： 消化系统恶性肿瘤光动力治疗(PDT)是新兴研究方向，其中光敏剂是治疗关键。课题组前期自主合成的二氢卟吩类光敏剂具优良抗肿瘤药效，鉴于该类光敏剂为结构非特异性药物，为提高其靶向性并开发诊治一体的靶向光敏剂，本课题：1）根据金纳米颗粒（AuNPS）具优良生物适应性和稳定性优势偶联光敏剂合成纳米递药系统，不仅提高光敏剂的被动靶向能力，其中AuNPS和光敏剂分别具CT和荧光成像效能；2）针对恶性肿瘤大麻素2型受体（CNR2）过度表达且与肿瘤侵袭密切相关特性，依靠前期建立的SELEX筛选平台拟优化获得更高特异性和选择性的CNR2适配体，再共价结合上述构建的金纳米光敏剂不仅提供优良生物相容性更提高其主动靶向效能。研究最终制备分子结构明确、生物相容性佳的靶向金纳米光敏剂，不仅可对恶性肿瘤进行荧光和CT影像诊断，更具备优良的光动力抗肿瘤疗效。

中文关键词： 适配体；大麻素；多模态；光敏剂；肿瘤靶向

英文摘要： Potodynamic therapy to treat the malignant tumor of digestive system is a new research direction. The photosensitizer is a key to treatment. Dihydrogen porphin photosensitizer we independent compounded shows good antitumor efficacy. In view of such photosensitizer was nonspecific structure, this study aim at developing a new targeting photosensitizer of both image diagnosis and treatment. 1) According to the advantages of excellent biological adaptability and stability of gold nanoparticles (AuNPS), when coupling with photosensitizer a new nano-drug delivery system was synthesized. It could enhance permeability and retention for passive targeting ability. Besides, AUNPS and photosensitizer have the potential of CT and fluorescence imaging repectively; 2) Based on cannabinoid receptor 2 (CNR2) over expressed in malignant tumor and closely related with tumor invasion, the established SELEX screening platform will be used for optimizing higher specificity and selectivity CNR2 aptamer. When covalent bonding to the photosensitizer, it not only provide excellent biocompatibility but also increase the efficiency of the active targeting. This study will have the targeted photosensitizer with clear molecular structure and good biocompatibility. The new targeted gold nanoparticle photosensitizer could not only provide diagnosis for Fluorescence and CT, but also provide photodynamic therapy.

英文关键词： aptamer;Cannabinoid;multimodality;Photosensitizer;tumor target