负载超顺磁性氧化铁及索拉非尼的叶酸靶向纳米胶束的制备、表征及磁共振响应特征  

Preparation, characterization and magnetic resonance＇s response characteristics of folate-functionilazed superparamagnetic iron oxide and sorafenib-loaded polymeric micelles

作　　者：马靖[1] 臧娴[2] 蒋媛媛[3] 张培东[2] 张芳[4] 巩发明[5] 张磊[2] 

机构地区：[1]广东省佛山市顺德第一人民医院普外二区,528300 [2]中山大学孙逸仙纪念医院肝胆胰外科 [3]中山大学孙逸仙纪念医院手术室 [4]中山大学孙逸仙纪念医院放射科 [5]中山大学化学与化学工程学院

出　　处：《中华实验外科杂志》2013年第11期2299-2301,共3页Chinese Journal of Experimental Surgery

基　　金：广东省自然科学基金资助项目（S2012010009741）;北京市希思科临床肿瘤学研究基金会资助项目（Y-B2012-001）

摘　　要：目的 探讨负载索拉非尼及超顺磁性氧化铁（SPIO）的叶酸靶向纳米胶束及非叶酸靶向纳米胶束的制备与表征,以及利用核磁共振成像术（MRI）监测纳米胶束对HepG2细胞的靶向性过程的可行性.方法 制备有叶酸修饰的负载索拉非尼及SPIO的纳米胶束（Fa-PEG-PCL-SPIONs）,以无叶酸修饰的负载索拉非尼及SPIO的纳米胶束作为对照,分别测量其粒径、超顺磁性及负载率等表征,然后将不同索拉非尼浓度（10.000、5.000、2.500、1.250、0.625 μmol/L）的叶酸靶向及非叶酸靶向纳米胶束分别与人肝癌细胞HepG2共孵育1h,以MRI观察共孵育后HepG2细胞T2加权成像（T2WI）上的信号强度及信号变化率的变化.结果 透射电镜显示叶酸靶向及非叶酸靶向聚合物纳米胶束制备成功,两者的粒径分别为74、80 nm,铁含量分别为16.3％、18.1％,索拉非尼含量分别为6.2％和6.6％；体外MRI显示叶酸靶向纳米胶束与人肝癌HepG2细胞共孵育后在T2WI上信号明显减低（索拉非尼浓度为10.000、5.000、2.500、1.250、0.625 μmol/L时,MRI信号变化率均值分别为-70.35％、-55.13％、-43.71％、-39.47％、-22.05％）,而非叶酸靶向胶束组信号无明显减低（索拉非尼浓度为10.000、5.000、2.500、1.250、0.625 μmol/L时,MRI信号变化率均值分别为-10.38％、-1.78％、-1.51％、-1.40％、-1.87％）.结论 成功制备具有超顺磁性的负载索拉非尼及SPIO的叶酸靶向纳米胶束及非叶酸靶向纳米胶束,并且纳米胶束对HepG2细胞的靶向性过程可以通过临床型MRI仪进行动态监测.Objective To prepare and analyze the physical characteristics of folate-functionalized superparamagnetle iron oxide （SPIO）-sorafenib-micelles （targeted micelles） and folate-free sorafenib and SPION-loaded mieelles （non-targeted micelles ） and to observe the feasibility of minitoring the targeting therapeutic effect with magnetic resonance imaging （MRI）. Methods SPION were loaded into polymeric micelles. The targeted nanocarrier was synthesized by funetionalizing the micelles with folate. Folate-free sorafenib and SPION-loaded micelles were used as controls. The physical characteristics of these nano-micelles including particle diameter, magnetic character, sorafenib or SPIO-loading contents, etc, were de- termined. MRI was performed to detect the signal intensity changes of cells after incubation with polymeric micelles at a clinical 1.5 T scanner. Reslflts The targeted micelles and non-targeted micelles were pre- pared successfully, and the physical characteristics of these nano-micelles were determined. Transmission electron microscope （TEM） showed that the micelles were of nano dimension. The magnetization curves of the micelles demonstrated that the SPIO-micelles had superparamagnetism. Sorafenib and SPIO-loaded contents were high. The T2 signal intensity on MRI of cells treated with targeted micelles was decreased signif- icantly with the increase of the concentration of sorafenib in cell culture medium, while no obvious signal was decreased for cells treated with the non-targeted micelles. Conclusion Folate-functionilazed SPIO andsorafenib-loaded polymeric micelles and folate-frec sorafenib and SPION-loaded micelles which have super paramagnetism were prepared successfully. The targeted inhibitory events of the micelles to HepG2 cells can be monitored using a clinical MRI unit.

关 键 词：超顺磁性氧化铁 索拉非尼 叶酸 核磁共振成像 纳米胶束 

分 类 号：R445.2[医药卫生—影像医学与核医学]