摘要
目的提高姜黄素溶解度,改善姜黄素对肿瘤的靶向性。方法以盐酸为变性剂,打开转铁蛋白(Tf)疏水性空腔,转铁蛋白的输水区域与姜黄素结合,制备转铁蛋白-姜黄素(CCM)纳米粒子(NPs-CCM)。通过透视电镜观察纳米粒子的粒径和形貌;通过转铁蛋白及其相关制剂荧光光谱的变化,推测纳米粒子的形成过程中转铁蛋白某些基团极性的变化;通过转铁蛋白水溶液加入盐酸和姜黄素后8-苯氨基-1-萘磺酸(ANS)荧光光谱的变化,观察纳米粒子形成过程中转铁蛋白表面疏水区域的变化,推测纳米粒子的自组装的过程;通过激光共聚焦检测纳米粒子在细胞中的蓄积情况,考察纳米粒子在体外的靶向性;通过近红外活体成像实验,观察纳米粒子在小鼠肿瘤部位及其他器官的蓄积,考察纳米粒子在体内的靶向性。结果NPs?CCM为直径40~150nm的球形颗粒。姜黄素的溶解度提高了200倍以上。在纳米粒子的形成过程中,转铁蛋白溶液加入盐酸后,酸使转铁蛋白变性,疏水区域暴露,姜黄素与酸变性的转铁蛋白结合后,疏水区域逐渐减少,通过酸对蛋白变性的作用形成转铁蛋白的自组装纳米粒子。在体内和体外的靶向实验中,NPs-CCM表现出较强的靶向性。结论纳米粒NPs-CCM是优良的CCM肿瘤靶向药物载体。
Objective To improve the solubility and targeting of curcumin to tumors.Methods Hydrochloric acid was used as a denaturing agent to open the hydrophobic cavity of transferrin(Tf).The hydrophobic region of transferrin was combined with curcumin to prepare transferrin-curcumin(CCM)nanoparticles(Nanoparticles,NPs-CCM).The particle size and morphology of the nanoparticles were observed by electron microscopy.The changes of the fluorescence spectra of transferrin and its related preparations were used to predict the polarity of certain groups of transferrin during the formation of nanoparticles.To predict the self-assembly process of nanoparticles,the changes of fluorescence spectra of ANS were used to speculate the hydrophobic region of transferrin.To speculate the targeting of nanoparticles in vitro,the accumulation of nanoparticles in cells was detected by laser confocal,and the nanoparticles were detected by near-infrared imaging including accumulation of NIR-797 and NIR-797 labelled nanoparticles at tumor sites and other organs in tumor loaded mice in vivo test.Results The NPs-CCM were about 40 to 150 nm with spherical shape. The solubility of nanoparticles is increased by more than 200 times.During the formation of the NPs-CCM,the hydrophobic region of Tf was exposed after the Tf solution being added with hydrochloric acid.Curcumin was combined with the acid-denatured transferrin after the acid denatures the transferrin.The hydrophobic region of Tf gradually reduced after the addition of CCM to the acid-denatured Tf solution.Self-assembled NPs-CCM is formed by denaturation of transferrin by hydrochloric acid.In tumor targeted experiments in vivo and in vitro,NPs-CCM showed targeting capability.Conclusion NPs-CCM are superior tumor-targeted nanocarrier system for CCM.
作者
朱庆
曹燕丽
徐云燕
龚光明
王曙东
ZHU Qing;CAO Yan-li;XU Yun-yan;GONG Guang-ming;WANG Shu-dong(School of Pharmacy,Nanjing University of Chinese Medicine,Nanjing 210046,Jiangsu,China;Department of Pharmaceutical Preparation,General Hospital of Eastern Theater Command,PLA,Nanjing 210002,Jiangsu,China)
出处
《东南国防医药》
2019年第3期262-266,共5页
Military Medical Journal of Southeast China
基金
国家自然科学基金(31671026)
