壳聚糖聚乳酸羟基乙酸纳米粒子作为抗瘤药物载体的研究  

The Study of Chitosan-PLGA Nanoparticles as Anti-Tumer Carriers

作　　者：马方奎[1] 包子娴[1] 陈西广[1] 

机构地区：[1]中国海洋大学海洋生命学院,山东青岛266003

出　　处：《中国海洋大学学报（自然科学版）》2014年第7期58-63,共6页Periodical of Ocean University of China

基　　金：国家自然科学基金项目(81271727);科技部国际合作专项(2013DFG32880)资助

摘　　要：研究采用乳化溶剂挥发技术和共价交联技术。合成了壳聚糖聚乳酸羟基乙酸（壳聚糖PLGA）的3种纳米载体：空白的PLGANPs、表面修饰的C-NPs和自组装的GNPs。利用人乳腺癌细胞MCF-7细胞作为模型细胞，抗肿瘤药物阿霉素为载药，通过荧光显微镜观察了肿瘤细胞对FITC标记的纳米载体的体外摄取情况，并进行了定量测定。用MTT法测定了包载药物阿霉素后纳米粒子对肿瘤细胞生长的抑制率，分析了不同纳米粒子作为抗肿瘤药物载体的靶向性和载药抑制性。研究结果表明，在低浓度条件下（25～400μg／mL），MCF-7细胞对C-NPs和G-NPs的吞噬具有时间依赖性和浓度依赖性。载药纳米粒子（DOX-PLGA NPs，DOX-C-NPs和DOX-G- NPs）和游离药物（DOX）对细胞生长的抑制率也具有时间依赖性和浓度依赖性，在低药物浓度下（1～4μg／mL）孵育12h后，载药纳米粒子基本呈现出高于游离药物的细胞生长抑制率，而当药物浓度从8μg／mL增加到16μg／mL后，游离阿霉索显现出更高的细胞生长抑制率，C-NPs和G-NPs均表现出高于PLGA NPs的细胞生长抑制率。壳聚糖修饰的2种纳米粒子C-NPs和G-NPs具有良好的细胞靶向性和低浓度药物抑制率，是一种良好的抗肿瘤药物载体。Surfaced modified Chitosan-PLGA nanoparticles （C-NPs） and self-assembled chitosan-PLGA nanoparticles （G-NPs） were prepared by emulsification solvent evaporation method and chemical conjugation method. The naked PLGA NPs were served as control. MCF-7 cells and doxorubicin （DOX） were chosen as the model cell and anti-tumor medicine. The in vitro cellular uptake and growth inhibition of C-NPs and G-NPs were evaluated by fluorescence microscopy and quantitative determination. The anti-tumor activity of DOX-loaded nanoparticles on MCF-7 cells and drug-loaded inhibition of different nanoparticles were assayed by MTT assay, analyzing the targeting as anti-tumor carriers. Results showed that in low concentration （25-40μg/mL）, the phagocytosis of C-NPs and G-NPs by MCF-7 cells were time and concentration dependent. The drug-loaded nanoparticles （DOX-PLGA NPs, DOX-C-NPs, DOX-G-NPs） and free DOX of growth inhibition for MCF-7 cells were time and concentration dependent as well. The drugloaded C-NPs and G-NPs cultured after 12 h in low concentrations （1-4 μg/mL） had higher cell growth inhibition rate than free DOX, while with the drug concentration increased from 8μg/mL to 16 μg/mL, free DOX presented higher cell growth inhibition rate, meanwhile C-NPs and G-NPs had higher cell growth inhibition rate than drugloaded PLGA nanoparticles carrier. Chitosan modified C-NPs and G-NPs were excellent anti-tumor drug-loaded carrier with good cell targeting and low concentration drug inhibition rate.

关 键 词：壳聚糖 聚乳酸羟基乙酸 阿霉素 纳米粒子 

分 类 号：R730.5[医药卫生—肿瘤]