透明质酸偶联壳聚糖微球对非小细胞肺癌的靶向性作用  

Targeting effect of hyaluronic acid coupled chitosan nanoparticles on non-small cell lung cancer

作　　者：梁恒伦[1] 李晶[2] 童健[1] 张福伟[1] 阮宝琴[1] 

机构地区：[1]南方医科大学附属珠江医院心胸外科,广东省广州市510282 [2]南方医科大学附属珠江医院肿瘤中心,广东省广州市510282

出　　处：《中国组织工程研究与临床康复》2011年第21期3847-3850,共4页Journal of Clinical Rehabilitative Tissue Engineering Research

摘　　要：背景:部分肿瘤细胞表面的CD44受体表达上调,如大肠癌、非小细胞肺癌,提示透明质酸与CD44受体在肿瘤的生长与扩散有着一定的关系。目的:观察透明质酸偶联壳聚糖纳米微球对非小细胞肺癌的靶向性。方法:采用离子交联法制备负载多西紫杉醇的透明质酸偶联壳聚糖微球(DTX-HACTNPs),电镜观察其形态学特征,激光粒度分析仪测定粒径大小及分布。FITC标记微球,作用于CD44+人非小细胞肺癌细胞株(A549),荧光显微镜观察。MTT法检测载药微球的体外细胞毒性。结果与结论:DTX-HACTNPs形态规则,粒径分布较为均匀,平均粒径为(228.0±2.6)nm。DTX-HACTNPs对A549细胞的杀伤力高于非透明质酸偶联载药微球,但仍低于普通注射用DTX,3者的半数抑制浓度(IC50)分别为(15.06±0.94),(25.73±3.37),(5.35±0.61)mg/L(F=73.871,P=0.000)。提示HACTNPs通过受体途径主动靶向性结合于非小细胞肺癌细胞,可提高化疗药对肿瘤细胞的选择性杀伤力。BACKGROUND：CD44 has been found to be over-expressed in non-small cell lung cancer（NSCLC）.Hyaluronic acid（HA）has a high affinity state with CD44 and has the potential as a targeted delivery vehicle for chemotherapy agents.OBJECTIVE：To evaluate the targeting effect of HA coupled chitosan nanoparticles（HACTNPs）on NSCLC.METHODS：HACTNPs bearing Docetaxel（DTX-HACTNPs）were prepared by ionotropic gelation.The nanoparticles were characterized for their shape by transmission/scanning electron microscopy.The particle size distribution was assessed by laser scattering.The biocompatibility of FITC-labeled nanoparticle formulations was evaluated for in vitro cytotoxicity by MTT assay using CD44＋A549 cell lines.RESULTS AND CONCLUSION：The DTX-HACTNPs appeared to be spherical in shape and the mean size was found to be around（228.0±2.6） nm with low polydispersity index.The cytotoxicity of DTX-HACTNPs was higher than that of DTX-CTNPs,but lower than that of conventional DTX for injection.And their IC50 were（15.06±0.94）,（25.73±3.37）,（5.35±0.61）mg/L,respectively（F=73.871,P=0.000）.The results indicate that HACTNPs are anticipated to be promising alternate carriers for targeting of CD44＋tumor cells.

关 键 词：药物靶向性输送 透明质酸 壳聚糖纳米微球 多西紫杉醇 非小细胞肺癌 

分 类 号：R318[医药卫生—生物医学工程]