癌症诊治用多功能复合脂质体的可控自组装

项目名称： 癌症诊治用多功能复合脂质体的可控自组装

项目编号： No.21273014

项目类型： 面上项目

立项/批准年度： 2013

项目学科： 数理科学和化学

项目作者： 戴志飞

作者单位： 北京大学

项目金额： 80万元

中文摘要： 化疗药物能显著增强光动力疗效，所以将光动力疗法与化疗联合已成为当前的研究热点。与化疗药物不同，光敏剂不需要释放。因此，如何用同一种纳米药物载体负载化疗药物和光敏剂对癌症进行化疗和光动力治疗是医药界面临的一个很大的挑战。申请人拟在已有基础上通过共价键将卟啉与脂质分子连接，合成含卟啉的复合脂质，并以此为自组装基元制备含卟啉的复合脂质体包埋阿霉素。一方面，脂质双层中以共价键连接的卟啉用于光动力荧光诊断与治疗，解决光敏剂泄漏的问题。另一方面，脂质体中包埋的阿霉素用于化疗，并通过调控脂质的自组装和Si-O-Si表面缩合度控制阿霉素的释放速度。脂质体表面存在的硅羟基使其具有很好的水分散性。通过硅羟基将叶酸等靶向分子连接到脂质体上，利用叶酸与叶酸受体间的特异性亲合力，使复合脂质体能有效地靶向定位于肿瘤组织部位。这样，可得到集靶向、药物控释、荧光诊断、光动力治疗与化疗于一体的多功能纳米复合脂质体。

中文关键词： 复合脂质；复合脂质体；光动力治疗；化疗；微泡

英文摘要： Chemotherapeutic drugs can enhance the efficiency of photodynamic therapy greatly, so chemotherapy combined with photodynamic therapy becomes a hot topic. Unlike chemotherapeutic drugs, photosensitizers do not need release during photodynamic therapy. Thus, it is a big challenge to use one naocarrier to co-deliver both chemotherapeutic drug and photosensitizer for chemotherapy combined with photodynamic therapy. Herein, the applicant synthesizes a new type of hybrid lipid by covalent attachment of porphyrin. Then, a nanohybrid liposome is fabricated from such hybrid lipid by self-assembly process for the encapsulation of doxorubicin. The porphyrins conjugated to the lipid bilayer of hybrid liposomes act as photosensitizer for photodynamic diagnosis and therapy without any leaking. Doxorubicin loaded in such liposomes can be used for chemotherapy. In addition, its release rate can be controlled by adjusting self-assembly process and Si-O-Si density of liposomes. Many hydroxyl groups exist on the surface of hybrid liposomes, making them more hydrophilic and dispersible in water. Folic acid can be attached onto the surface of liposomes by the reaction between folic acid and hydroxyl groups so the hybrid liposomes can be targetedly delivered to the tumor. Thus, we can construct multifunctional nanohybrid liposomes w

英文关键词： hybrid lipid；hybrid liposome；photodynamic therapy；chemotherapy；microbubble