金纳米粒调控的新型细胞内递药系统用于人参皂苷和紫杉醇联合抗肿瘤研究

项目名称： 金纳米粒调控的新型细胞内递药系统用于人参皂苷和紫杉醇联合抗肿瘤研究

项目编号： No.81202925

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 医学八处

项目作者： 钮萌萌

作者单位： 上海中医药大学

项目金额： 23万元

中文摘要： 癌症是威胁人类健康的重要疾病，现有的抗肿瘤药物选择性差，不良反应大，很多肿瘤细胞存在多药耐药的特点，极大地影响了抗肿瘤药物的疗效。本项目拟以金纳米粒作为药物的载体，选择可以发挥协同作用的两种中药抗肿瘤活性单体紫杉醇和人参皂苷Rh2与金纳米粒形成稳定的复合物，再将复合物载于脂质体中，形成包载了药物-金纳米粒复合物的脂质体（Drug-GNPs complex in liposomes）给药系统。该系统结合了金纳米粒与脂质体各自的优点，具有载药量大、载药种类多、比单一金纳米粒或脂质体具有对细胞更强的亲和性，更容易实现细胞内药物的高浓度递送，有望克服肿瘤的多药耐药性，提高抗肿瘤药物的抑瘤效果。此外，利用金纳米粒受到光照后产热的特点还可以随时调控药物的释放,减少了药物提前释放对正常身体组织的伤害。该递药系统可以为抗肿瘤药物提供一种低毒高效的治疗手段。其构建模式及相关研究国内外均未见报道。

中文关键词： 金纳米粒；脂质体；抗肿瘤中药；多药耐药；控制释放

英文摘要： Cancer is one of the primary diseases threatening human life. Using chemotherapy often results damage to normal tissues, besides, multidrug resistance (MDR) of cancer cells seriously reduces the efficacy of many chemotherapy agents, standing an obstacle in the cancer fields. Nanoparticles enjoy enhanced improvement in cancer treatment and recently, a novel inorganic nanoparticles - gold nanoparticles (AuNPs) has attracted attention because of their high tissue permeability, high colloidal stability, and small size. Drugs can be easily grafted onto AuNPs via physical adsorption, ionic bonding, and covalent bonding. In this study, we developed drug-AuNPs nanoconjugateds by grafting two cotherapy drugs to the surface of AuNPs, which will be further loaded on to folic acid-modified liposomes. This DDS possesses its advantages of intracellular drug delivery for two antitumor drugs and play their synergistic treatment, thus to overcome the MDR problem, besides, light can be used as an external stimulus to release a drug from AuNPs and avoids the irregular drug release in physiological conditions. Based on these features, this vehicle provides an efficient and safe way to deliver drugs to drug -resistant tumor cells and serves as a novel DDS in the pharmaceutical field.

英文关键词： gold nanoparticles；liposomes；Traditional Chinese medicine anti-tumor drug；multiple drug resistance；controlled release