双靶向多功能纳米载体的构建与评价  

Design and evaluation of dual targeting multifunctional nanocarrier

作　　者：宋晓燕[1] 王晓英 亓梦娇 董雪[1] 王凯丽 郭春静[1] 陈大全[1] 

机构地区：[1]烟台大学新型制剂与生物技术药物研究山东省高校协同创新中心,烟台264005 [2]中国人民解放军第107医院,烟台264002

出　　处：《中国新药杂志》2018年第2期207-213,共7页Chinese Journal of New Drugs

基　　金：国家自然科学基金资助项目(81573614);烟台大学研究生科技创新基金资助项目(YDYB1726);泰山学者工程专项经费资助(qnts20161035);烟台市科技发展计划资助项目(2015ZH079)

摘　　要：目的:构建并评价一种CD44受体和叶酸受体双靶向的pH敏感纳米载体。方法:以pH敏感性的缩醛-薄荷缩酮(acetal-menthone 1,2-glycerol ketal,Ace-MGK)作为疏水端,寡聚透明质酸(oligomeric hyaluronic acid,o HA)和叶酸(folic acid,FA)分别作为CD44受体和叶酸受体靶标,合成具有智能化响应的多功能纳米靶向Fo AM载体材料。通过傅里叶变换红外光谱法(IR)和核磁共振技术(~1H-NMR)对该载体材料进行结构鉴定。以姜黄素(curcumin,Cur)作为模型药物,通过透析法制得载姜黄素纳米胶束,并对其平均粒径、Zeta电位及形态进行表征。结果:成功合成Fo AM载体材料,制备的Fo AM载药胶束能够自组装为球形形态,平均粒径为158.2 nm,Zeta电位为-24.51 m V。结论:Fo AM作为一种高效的纳米给药载体在抗肿瘤给药领域中具有潜在的应用前景。Objective： To develop and evaluate dual CD44 receptor and folate receptor targeting pH-sensitive nanocarrier. Methods： The smart response muhifunctional oligomeric hyaluronic acid conjugate, folic acid- oligomeric hyaluronic acid-acetal-menthone 1,2-glycerol ketal （FA-oHA-Ace-MGK） , was synthesized by chemical reaction. The pH-sensitive Ace-MGK as hydrophobic moieties, oHA as the target of CD44 receptor and FA as the target of folate receptor. The structure of this dual CD44 receptor and folate receptor targeting smart response muhifunctional nanocarrier was confirmed with Fourier-transform infrared and nuclear magnetic resonance （1H-NMR）. The micelles of this nanocarrier were loaded with curcumin （Cur） , a model drug, by dialysis method, and were characterized by mean diameter, zeta potential and morphology visualized by transmission electron microscopy （TEM）. Results： FoAM nanocarrier was synthesized successfully. Drug-loaded FoAM could self-assemble to form spherical nanoparticles with the mean diameter of 158.2 nm and zeta potential of -24.51 mV. Conclusion： FOAM, as an effective nano-size carrier, has a promising potential for anti-tumor drug delivery.

关 键 词：双靶向 多功能 PH敏感 靶向载体 

分 类 号：R943[医药卫生—药剂学]