中国组织工程研究 ›› 2011, Vol. 15 ›› Issue (21): 3847-3850.doi: 10.3969/j.issn.1673-8225.2011.21.011

• 药物控释材料 drug delivery materials • 上一篇    下一篇

透明质酸偶联壳聚糖微球对非小细胞肺癌的靶向性作用

梁恒伦1,李  晶2,童  健1,张福伟1,阮宝琴1   

  1. 南方医科大学附属珠江医院,1心胸外科,2肿瘤中心,广东省广州市  510282
  • 收稿日期:2011-02-21 修回日期:2011-04-24 出版日期:2011-05-21 发布日期:2011-05-21
  • 通讯作者: 童健,教授,硕士生导师,南方医科大学附属珠江医院心胸外科,广东省广州市 510282 Tongjian@hotmail.com
  • 作者简介:梁恒伦★,男,1983年生,广东省肇庆市人,汉族,南方医科大学在读硕士,医师,主要从事肺癌综合治疗的研究。 liangalun2008@yahoo.com.cn

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

Liang Heng-lun1, Li Jing2, Tong Jian1, Zhang Fu-wei1, Ruan Bao-qin1   

  1. 1Department of Cardiothoracic Surgery, 2Oncology Center, Zhujiang Hospital, Southern Medical University, Guangzhou  510282, Guangdong Province, China
  • Received:2011-02-21 Revised:2011-04-24 Online:2011-05-21 Published:2011-05-21
  • Contact: Tong Jian, Professor, Master’s supervisor, Department of Cardiothoracic Surgery, Zhujiang Hospital, Southern Medical University, Guangzhou 510282, Guangdong Province, China Tongjian@hotmail.com
  • About author:Liang Heng-lun★, Studying for master’s degree, Physician, Department of Cardiothoracic Surgery, Zhujiang Hospital, Southern Medical University, Guangzhou 510282, Guangdong Province, China liangalun2008@yahoo.com.cn

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。

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

Abstract:

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.

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