透明质酸偶联壳聚糖微球对非小细胞肺癌的靶向性作用★

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。

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

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.