Hyaluronic acid derivative-modified nano-structured lipid carrier for cancer targeting and therapy  

透明质酸衍生物修饰脂质纳米载体的抗肿瘤作用及体内靶向研究

作　　者：Xiao LIU Hai LIU Su-lan WANG Jing-wen LIU 

机构地区：[1]Department of Pharmacy,Sir Run Run Shaw Hospital,School of Medicine,Zhejiang University,Hangzhou 310016,China [2]Department of Radiotherapy,Sir Run Run Shaw Hospital,School of Medicine,Zhejiang University,Hangzhou 310016,China [3]Department of Pharmacological and Pharmaceutical Sciences,College of Pharmacy,University of Houston,Hangzhou 310016,China

出　　处：《Journal of Zhejiang University-Science B(Biomedicine & Biotechnology)》2020年第7期571-580,共10页浙江大学学报（英文版）B辑（生物医学与生物技术）

基　　金：Project supported by the Zhejiang Provincial Natural Science Foundation of China(No.LY14H160016)。

摘　　要：To reduce the problems of poor solubility,high in vivo dosage requirement,and weak targeting ability of paclitaxel(PTX),a hyaluronic acid-octadecylamine(HA-ODA)-modified nano-structured lipid carrier(HA-NLC)was constructed.HA-ODA conjugates were synthesized by an amide reaction between HA and ODA.The hydrophobic chain of HA-ODA can be embedded in the lipid core of the NLC to obtain HA-NLC.The HA-NLC displayed strong internalization in cluster determinant 44(CD44)highly expressed MCF-7 cells,and endocytosis mediated by the CD44 receptor was involved.The HA-NLC had an encapsulation efficiency of PTX of 72.0%.The cytotoxicity of the PTXloaded nanoparticle HA-NLC/PTX in MCF-7 cells was much stronger than that of the commercial preparation Taxol.In vivo,the HA-NLC exhibited strong tumor targeting ability.The distribution of the NLCs to the liver and spleen was reduced after HA modification,while more nanoparticles were aggregated to the tumor site.Our results suggest that HA-NLC has excellent properties as a nano drug carrier and potential for in vivo targeting.目的:以脂质纳米载体为递药系统向肿瘤部位靶向输送难溶性抗肿瘤药物紫杉醇,实现药物的靶向递送。创新点:采用一端疏水化的透明质酸修饰脂质纳米载体,利用透明质酸与肿瘤部位高表达CD44的特异性结合,实现载药脂质纳米粒的靶向输送。方法:通过酰胺反应,将硬脂胺化学嫁接至透明质酸,制备透明质酸-硬脂胺嫁接物。采用水性溶剂扩散法制备脂质纳米粒,并将透明质酸-硬脂胺嫁接物插入脂质纳米粒的表面。使用红外染料Di R标记脂质纳米粒,通过小动物活体成像技术观察标记脂质纳米粒的体内分布。结论:透明质酸修饰的脂质纳米粒,可通过与CD44的特异性结合,实现抗肿瘤药物的靶向递送。

关 键 词：Paclitaxel(PTX) Hyaluronic acid-octadecylamine(HA-ODA) Nano-structured lipid carrier(NLC) Tumor targeting In vivo distribution 

分 类 号：R943[医药卫生—药剂学] R96[医药卫生—药学]