【作者】 张金叶； 周亭； 王秀凤； 张国栋； 王芳； 张志庆；

【Author】 Jinye Zhang;Ting Zhou;Xiufeng Wang;Guodong Zhang;Fang Wang;Zhiqing Zhang;School of science,China University of Petroleum(East China);

【机构】 中国石油大学(华东)理学院；

【摘要】 靶向给药用于癌症的治疗是近些年来的研究热点,而如何制备无害的、可设计的、大小可控的纳米药物载-递体系是该项研究的重点。本文报告了一种自组装PTK7-适配体DNA胶束的设计,疏水基团引入分子结构可以形成疏水内核增溶药物分子,同时增加了PTK7-适配体DNA胶束的生物相容性;DNA链既可以起到亲水作用又可以形成双螺旋结构为药物分子提供更多的结合位点,进一步增强胶束的载药能力;并且该胶束中含有PTK7适配体,通过PTK7靶标蛋白对白血病细胞的特异性识别,实现抗癌药物的靶向递送,从而对癌细胞实现抑制或者杀灭。该适配体DNA胶束具有制备便捷、临界胶束浓度低、载药能力强以及生物相容性好等优点。DNA胶束的大小及形貌通过动态光散射、AFM以及TEM进行表征;利用紫外分光光度法测定了胶束的包封率、载药量;并且通过渗析法模拟药物体外释放,考察纳米胶束的体外释药特性;采用细胞实验测定适配体DNA胶束对于癌细胞特异性识别及杀灭能力。更多还原

【Abstract】 In recent years, targeted drug delivery for the treatment of cancer has been given the increasing attention, and preparing safe, designable and controllable nano-drug carrier-delivery system is the emphasis of future research. In this paper, PTK7-aptamer DNA micelle is designed, characterized and evaluated for targeted doxorubicin tumor therapy. Hydrophobic group is introduced in PTK7-aptamer DNA micelle to form hydrophobic core for the solubilization of poorly-soluble drug. Moreover, it could increase the biocompatibility of PTK7-aptamer DNA micelles. DNA strands could not only play a hydrophilic role in micelles, but also form duplex and drug-loading domains by hybridizing with complementary strands. In addition, PTK7 aptamer in the micelles can specifically recognize the leukemia cells by PTK7 target protein to enhance targeted delivery of anticancer drugs. The PTK7-aptamer DNA micelles own the advantages of simple preparation, low critical micelle concentration, a high drug loading capacity and low cytotoxicity. The size and morphology of DNA micelles were characterized by dynamic light scattering, AFM and TEM. The encapsulation rate and drug loading capacity of micelles were determined by UV-vis spectrophotometry. Dialysis method was used to evaluate the drug release capacity in vitro. Cellular uptake and cytotoxicity were conducted to extensively evaluate the potential of PTK7-aptamer DNA micelles as promising drug nanocarriers.更多还原