有机/无机杂化纳米药物输运系统的设计、制备及其在药物共输运中的应用探索

项目名称： 有机/无机杂化纳米药物输运系统的设计、制备及其在药物共输运中的应用探索

项目编号： No.51302293

项目类型： 青年科学基金项目

立项/批准年度： 2014

项目学科： 一般工业技术

项目作者： 陈雨

作者单位： 中国科学院上海硅酸盐研究所

项目金额： 25万元

中文摘要： 本项目通过设计与制备一种在分子层次高度有机/无机杂化的新型介孔有机硅空心纳米粒子（HPMOs），克服传统无机质介孔SiO2纳米粒子（MSNs）降解性和生物相容性较差的难题。进一步通过HPMOs空心纳米结构和介孔孔道的调控实现两种具有不同功效的抗癌药物分子的共负载，实现逆转肿瘤细胞耐药性、抑制肿瘤细胞转移和降低抗癌药物毒副作用的多重目的。本项用创新采用SiO2刻蚀化学调控HPMOs的分散性和粒径、孔径、组成、壁厚、空腔大小等关键结构参数；系统地评价该有机/无机杂化纳米粒子的生物降解性与细胞生物学效应；通过体外与体内动物乳腺癌模型（MCF-7/ADR耐药模型和4T1转移模型）研究HPMOs共负载抗癌药物的药效，并考察其作用机制。本项目的开展将对纳米合成化学的发展和实现肿瘤的高效化疗具有重要的意义，有望推动无机纳米生物材料的临床应用。

中文关键词： 介孔有机硅；空心结构；药物输运；纳米医学；肿瘤治疗

英文摘要： This project will design and synthesize a new type of molecularly organic/inorganic hybrid hollow periodic mesoporous organosilica nanoparticles (HPMOs) to overcome the drawbacks of tranditional inorganic mesoporous silica nanoparticles (MSNs), such as low degradation rates and their biocompatibility. Furthermore, the hollow nanostructure and mesopores will be tailored to co-load two types of anticancer drugs with different functions. Such co-loading and co-delivery of anticancer drugs can reverse the multi-drug resistance of cancer cells,restrict the metastasis of cancer cells and reduce the side-effects of anticancer drugs. This project innovatively employs the SiO2-based etching chemistry to design and prepare HPMOs with tailored dispersity, particle sizes, pore sizes, compositions, shell-thickness, etc..The biodegradation and biological effects will be systematically investigated. The anticancer effects of co-loaded HPMOs will be evaluated from in vitro to in vivo (breast cancer models of multidrug-resistant MCF-7/ADR and metastatic 4T1), and the detailed mechanism will be studied. The launching of this project will play the significant role for the development of nano-synthetic chemistry and achievement of chemotherapy with high efficiency, which will further give the strong impetus to the clinical applicat

英文关键词： Mesoporous organosilica；Hollow structure；Drug delivery；Nanomedicine；Cancer therapy