中国组织工程研究

中国组织工程研究 ›› 2010, Vol. 14 ›› Issue (21): 3861-3864.doi: 10.3969/j.issn.1673-8225.2010.21.014

• 纳米生物材料 nanobiomaterials • 上一篇    下一篇

人转铁蛋白修饰载阿霉素海藻酸钠纳米粒的制备与评价

钟  珍，苏  科，周汉新，李富荣，齐  晖   

  1. 暨南大学第二临床学院，深圳市人民医院临床医学研究中心，广东省深圳市  518020
  • 出版日期:2010-05-21 发布日期:2010-05-21
  • 通讯作者: 齐 晖，研究员，暨南大学第二临床学院临床医学研究中心，广东省深圳市 518020 qihui214@hotmail.com
  • 作者简介:钟 珍★，女，1983年生，湖北省仙桃市人，汉族，暨南大学第二临床学院在读硕士，主要从事医用生物材料类的研究。 zhongzhen215@163.com

Preparation and evaluation of doxorubicin-loaded alginate nanoparticles modified by human transferrin

Zhong Zhen, Su Ke, Zhou Han-xin, Li Fu-rong, Qi Hui   

  1. Second Clinical College of Jinan University, Clinical Medical Research Center of Shenzhen People’s Hospital, Shenzhen   518020, Guangdong Province, China
  • Online:2010-05-21 Published:2010-05-21
  • Contact: Qi Hui, Investigator, Second Clinical College of Jinan University, Clinical Medical Research Center of Shenzhen People’s Hospital, Shenzhen 518020, Guangdong Province, China qihui214@hotmail.com
  • About author:Zhong Zhen★, Studying for master’s degree, Second Clinical College of Jinan University, Clinical Medical Research Center of Shenzhen People’s Hospital, Shenzhen 518020,Guangdong Province, China zhongzhen215@163.com

PDF

458

被引次数

8

摘要：

背景：对抗肿瘤药物靶向治疗和肿瘤细胞多药耐药产生的问题，载阿霉素海藻酸钠纳米粒经改性，偶联人转铁蛋白，生成的人转铁蛋白修饰载药纳米粒，可用于靶向肿瘤药物载体。
目的：制备人转铁蛋白修饰的载阿霉素海藻酸钠纳米粒并进行表征鉴定，检测其表面蛋白活性。
方法：采用优化的微乳化-离子交联方法制备包覆阿霉素的海藻酸钠复合纳米粒，以水溶性碳二亚胺为交联剂,将载阿霉素海藻酸钠纳米粒与人转铁蛋白连接，制备出人转铁蛋白修饰载阿霉素海藻酸钠纳米粒。透射电镜观察纳米粒的外观大小、形态；高效液相色谱法分析纳米粒的包封率和载药量；流式细胞仪检测其表面人转铁蛋白的活性。
结果与结论：人转铁蛋白修饰载阿霉素海藻酸钠纳米粒呈球形，平均粒径为170 nm。阿霉素的加入量可影响纳米粒的包封率，当阿霉素的加入量为纳米粒的10%时，包封率和包裹量均最佳。每毫克载药纳米粒可与约65 μg人转铁蛋白连接。人转铁蛋白修饰的载药纳米粒在流式细胞仪上除去非特异性吸附后还有67.3%荧光显示，说明人转铁蛋白修饰的载药纳米粒大部分都偶联上了人转铁蛋白抗体并能保持抗体活性，从而为载药纳米粒特异性靶向肿瘤细胞提供了足够的靶向动力。微乳化-离子交联方法制备方法简便可靠，制得的人转铁蛋白修饰载阿霉素海藻酸钠纳米粒有望成为具有潜在价值的一种特异性靶向药物载体。

关键词: 海藻酸钠, 阿霉素, 人转铁蛋白, 纳米粒, 靶向, 生物材料与纳米技术

Abstract:

BACKGROUND: For the problems of antitumor drugs targeted therapy and tumor cell multidrug resistance, doxorubicin-loaded alginate nanoparticles improved by coupling human transferrin can be used for targete tumor drug delivery.
OBJECTIVE: To prepare the doxorubicin-loaded alginate nanoparticles modified by human transferrin, to study the characterization and to evaluate the surface protein activities.
METHODS: By means of optimized microemulsion-ionic crosslinking, doxorubicin-loaded alginate nanoparticles were prepared, water-soluble carbodiimide served as a crosslinking agent, then sodium alginate nanoparticles were connected with human transferrin to prepare human transferrin-modified alginate nanoparticles loading doxorubicin. The size and morphology of drug-loaded nanoparticles modified by human transferrin was observed by transmission electron microscope. Encapsulation capability and loading content were analyzed by high-performance liquid chromatography. The immunological activity of human transferrin on the nanoparticles were detected by flow cytometer.
RESULTS AND CONCLUSION: The doxorubicin-loaded alginate nanoparticles modified by human transferrin were round shaped, their mean diameters averaged 170 nm. The dose of doxorubicin could affect the encapsulation rate of the nanoparticles, which achieved the optimal encapsulation efficiency and loading content when adding 10% doxorubicin into nanoparticles. It was about 65 μg human transferrin per milligram of the nanoparticles. The nanoparticles displayed 67.3% fluorescent when eliminated non-specific adsorption on the flow cytometer, which illustrated that most doxorubicin-loaded alginate nanoparticles could couple on the human transferrin antibody and maintained its antibody activity, thus providing sufficient target power for drug-loaded nanoparticles specific targeting to tumor cells. The microemulsion-ionic crosslinking method is reliable and simple, the obtained doxorubicin-loaded alginate nanoparticles modified by human transferrin can be a potential specific targeted drug carrier.

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