文献类型：期刊文献

中文题名：pH响应MSNs@polymer(FITC/FA)核-壳结构双重药物载体

英文题名：pH-Sensitive MSNs@polymer(FITC/FA) with Core-Shell Structure Used for Double-Drug Carriers

作者：昌慧[1,2];郝伟举[1,2];刘洪来[3];徐首红[1,2]

机构：[1]华东理工大学结构可控先进功能材料及其制备教育部重点实验室,上海200237;[2]华东理工大学化学与分子工程学院,上海200237;[3]华东理工大学化工学院,上海200237

年份：2019

卷号：45

期号：4

起止页码：548

中文期刊名：华东理工大学学报（自然科学版）

外文期刊名：Journal of East China University of Science and Technology

收录：CSTPCD;;Scopus;北大核心:【北大核心2017】；CSCD:【CSCD_E2019_2020】；

基金：国家自然科学基金(21276074);国家自然基金创新研究群体(51621002)

语种：中文

中文关键词：纳米颗粒;pH敏感;靶向运输;核-壳结构

外文关键词：nanoparticles;pH sensitivity;targeted transport;core-shell structure

摘要：通过原子转移自由基聚合(ATRP)在介孔二氧化硅纳米颗粒(MSNs)表面接枝具有pH响应的聚2-(二异丙基氨基)甲基丙烯酸乙酯(PDPA),点击化学修饰聚乙二醇(PEG)、叶酸(FA)及荧光基团异硫氰酸荧光素(FITC),制备无机/有机复合材料的核-壳结构纳米颗粒(MSNs@polymer(FITC/FA)).通过细胞实验证明了所合成的纳米颗粒的生物相容性以及对于肿瘤细胞的靶向性和示踪性,结果表明该纳米颗粒可以同时在核层和壳层分别包载抗肿瘤药物紫杉醇(PTX)和多药耐药逆转剂他克莫司(FK506),其释药动力学研究结果显示在生理环境pH 7.4的条件下仅有约20%的药物泄漏,在pH 5.0的条件下存在24 h后超过80%的药物可以被释放.实验证明通过使药物分别分布在核层和壳层,可实现药物的分阶段释放.MSNs@polymer(FITC/FA)有望解决临床上抗肿瘤药物的多药耐药性问题.
Smart drug carrier can precisely deliver drugs to the disease sites, improving the drug efficacy and reducing the side effects. In this paper, MSNs@polymer (FITC/FA) were prepared through grafting pH-sensitive poly(2-(Diisopropyl amino) ethyl methacrylate)(PDPA), polyethylene glycol (PEG) and folic acid/fluorescence (FA/FITC) onto the surface of mesoporous silica(MSNs) using atom transfer radical polymerization (ATRP) and click chemistry. The system was developed by using the polymer as an end-capping group to seal the mesopores of MSNs, which is used for intracellular acid triggered drug release. A series of characterization techniques were applied to characterize and confirm the structures of the intermediates and the core-shell structured nanoparticles (MSNs@polymer(FITC/FA)) composing of inorganic and organic composite. The cell experiments including flow cytometry analysis, confocal laser scanning microscopy observations and cytotoxicity studies suggested that the nanocarriers were efficiently endocytosed by HeLa cancer cells, indicating the good biocompatibility of the nanoparticles, and their targeting and traceability for tumor cells. The nanoparticles could load both the antitumor drugs of paclitaxel (PTX) and tacrolimus (FK506) in the core and shell layers, respectively. PTX and FK506 were easily encapsulated into the nanocarriers with a high loading capacity, and were quickly released in response to the stimuli of acid. The drugs leakage was only about 20% under neutral condition (pH 7.4), but reached more than 80% at pH 5.0 after 24 h. Furthermore, it was proved that the two drugs could be released successively when the drugs were loaded into the core and shell, respectively. MSNs@polymer(FITC/FA) are expected to solve the problem of multi-drug resistance of antitumor drugs in clinic.