CAJ | 학술논문

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.
목적 탐토부재색랍비니급초순자성양화철(SPIO)적협산파향납미효속급비협산파향납미효속적제비여표정,이급이용핵자공진성상술(MRI)감측납미효속대HepG2세포적파향성과정적가행성.방법 제비유협산수식적부재색랍비니급SPIO적납미효속(Fa-PEG-PCL-SPIONs),이무협산수식적부재색랍비니급SPIO적납미효속작위대조,분별측량기립경、초순자성급부재솔등표정,연후장불동색랍비니농도(10.000、5.000、2.500、1.250、0.625 μmol/L)적협산파향급비협산파향납미효속분별여인간암세포HepG2공부육1h,이MRI관찰공부육후HepG2세포T2가권성상(T2WI)상적신호강도급신호변화솔적변화.결과 투사전경현시협산파향급비협산파향취합물납미효속제비성공,량자적립경분별위74、80 nm,철함량분별위16.3％、18.1％,색랍비니함량분별위6.2％화6.6％；체외MRI현시협산파향납미효속여인간암HepG2세포공부육후재T2WI상신호명현감저(색랍비니농도위10.000、5.000、2.500、1.250、0.625 μmol/L시,MRI신호변화솔균치분별위-70.35％、-55.13％、-43.71％、-39.47％、-22.05％),이비협산파향효속조신호무명현감저(색랍비니농도위10.000、5.000、2.500、1.250、0.625 μmol/L시,MRI신호변화솔균치분별위-10.38％、-1.78％、-1.51％、-1.40％、-1.87％).결론 성공제비구유초순자성적부재색랍비니급SPIO적협산파향납미효속급비협산파향납미효속,병차납미효속대HepG2세포적파향성과정가이통과림상형MRI의진행동태감측.
Objective To prepare and analyze the physical characteristics of folate-functionalized superparamagnetic iron oxide (SPIO)-sorafenib-micelles (targeted micelles) and folate-free sorafenib and SPION-loaded micelles (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 functionalizing 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 determined.MRI was performed to detect the signal intensity changes of cells after incubation with polymeric micelles at a clinical 1.5 T scanner.Results The targeted micelles and non-targeted micelles were prepared 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 significantly 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 and sorafenib-loaded polymeric micelles and folate-free sorafenib and SPION-loaded micelles which have superparamagnetism were prepared successfully.The targeted inhibitory events of the micelles to HepG2 cells can be monitored using a clinical MRI unit.