基于海藻酸钠衍生物的肝靶向纳米前药的构建及抗肿瘤活性研究  

Preparation of Liver-targeted Nano-prodrug Based on Sodium Alginate Derivative and the Study on Antitumor Activity

作　　者：郭华[1] 杨承玲 王蔚[1] 赖全勇[1] 袁直[1] 

机构地区：[1]南开大学高分子化学研究所,功能高分子材料教育部重点实验室,天津化学化工协同创新中心,天津300071

出　　处：《高等学校化学学报》2014年第8期1835-1842,共8页Chemical Journal of Chinese Universities

基　　金：国家自然科学基金(批准号:51073080;51273095);天津市自然科学基金(批准号:13JCYBJC25100);教育部创新团队PCSIRT项目(批准号:IRT1257)资助~~

摘　　要：利用寡聚乙二醇(mOEG)修饰海藻酸钠(ALG),有效降低了ALG的黏度,提高了其对疏水性肝靶向配体甘草次酸(GA)的负载量.结果表明,靶向材料(GA-ALG-mOEG)的GA负载量为11.8%,是对照组(GAALG)的1.97倍.在此基础上,以物理交联的方式引入pH响应的阿霉素前药(DOX-ALG-mOEG),制备了肝靶向纳米前药(DOX-ALG-mOEG/GA-ALG-mOEG NPs).细胞实验及抑瘤实验结果表明,该前药较对照组(DOX-ALG/GA-ALG NPs)具有更高的肝靶向性和药物利用率,其对肝癌细胞的半致死率浓度(IC50)为58.1ng/mL,是对照组(IC50=141.7 ng/mL)的41%;动物实验结果显示,该前药的抑瘤率达到了88.4%,比对照组提高了11.5%.The high viscosity of sodium alginate（ ALG） causes its insufficient targeted ligand loading, and further influences the targeted recognition effect of nano-prodrug. Here, oligomeric ethylene glycol modified-sodium alginate（ ALG-mOEG） was used as a carrier to improve the targeted-ligands loading. Results showed that ALG-mOEG significantly improved glycyrrhetinic acid （ GA ） loading compared with unmodified ALG （11.8% vs. 6.9%, 1.97-fold increase） . On this basis, the liver targeted nano-prodrug（ DOX-ALG-mOEG/GA-ALG-mOEG NPs ） was self-assembled via dialysis method by mixing GA-ALG-mOEG and DOX-ALG-mOEG. Cell cytotoxicity experiment showed that DOX-ALG-mOEG/GA-ALG-mOEG NPs inhibited HepG2 proliferation with an half maximal inhibitory concentration（ IC50 ） value of 58.1 ng/mL while the IC50 of control group was 141.7 ng/mL;the tumor growth inhibition rate（ IR） reached to 88.4%, improved by 11.5% com-pared to that of the control group. This study show that the liver targeted nano-prodrug based on ALG-mOEG can effectively improve the drug utilization, and provide a reference for the preparation of other polysaccharide targeted nano-prodrug.

关 键 词：海藻酸钠衍生物 寡聚乙二醇 甘草次酸 抗肿瘤活性 

分 类 号：O631[理学—高分子化学] O636.9[理学—化学]