Superparamagnetic iron oxide nanoparticles conjugated with folic acid for dual target-specific drug delivery and MRI in cancer theranostics
Superparamagnetic iron oxide nanoparticles conjugated with folic acid for dual target-specific drug delivery and MRI in cancer theranostics
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与叶酸结合的超顺磁性氧化铁纳米粒子用于癌症治疗诊断中的双靶点特异性药物输送和 MRI
DOI：
10.1016/j.msec.2016.09.052
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发表时间：
2017-01-01
影响因子：
7.9
通讯作者：
Zhao, Yingzheng
中科院分区：
文献类型：
--
作者：
Huang, Yinping;Mao, Kaili;Zhao, Yingzheng
采用改进的多元醇法制备了单分散的聚乙二醇（PEG）和聚乙烯亚胺（PEI）聚合物共包覆的超顺磁性氧化铁纳米粒子（SPION）。为了实现肿瘤特异性靶向性，采用EDC/NHS方法对SPION进行叶酸修饰（FA-SPION），并将阿霉素（DOX）作为抗癌药物负载于FA-SPION（DOX@ FA-SPION）中，DOX@ FA-SPION在低pH PBS中的释放速率非常高。平均流体动力学直径分别为23、40和67 nm的SPION、FA-SPION和DOX@ FA-SPION在PBS中表现出优异的胶体稳定性。共聚焦激光扫描显微镜（CLSM）研究表明DOX@ FA-SPION通过FA受体介导的内吞作用有效靶向MCF-7细胞。DOX@ FA-SPION通过尾静脉注射在具有异种移植MCF-7乳腺肿瘤的裸鼠中进行测试，发现其更有效地抑制肿瘤生长。磁场（MF）的应用大大提高了DOX@ FA-SPION在体外对MCF-7细胞和在体内对裸鼠异种移植物MCF-7乳腺肿瘤的生长抑制效率。由于DOX@ FA-SPION表现出高的r（2）弛豫率（81：77 mM（-1）S（-1）），因此通过磁共振成像（MRI）监测SPION在肿瘤中的聚集。小鼠肝、肺、肾和心脏的组织学显示，DOX@ FA-SPION治疗35天后对小鼠器官无明显毒性。FA-SPION是晚期癌症治疗诊断学的高效药物递送纳米平台。(C)2016爱思唯尔B. V.保留所有权利。
Monodispersed SPIONs (superparamagnetic iron oxide nanoparticles) co-coated with PEG and PEI polymers were prepared by an improved polyol method. To accomplish cancer-specific targeting properties, FA (folic acid) was then modified on the SPIONs via EDC/NHS method (FA-SPIONs).Doxorubicin (DOX) as an example anticancer drug was loaded within FA-SPIONs (DOX@FA-SPIONs), the DOX release rate of DOX@FA-SPIONs was much high in low pH PBS. The SPIONs, FA-SPIONs and DOX@FA-SPIONs with mean hydrodynamic diameters of 23, 40 and 67 nm, respectively, performed excellent colloidal stability in PBS. Confocal laser scanning microscope (CLSM) study implicates that the DOX@FA-SPIONs target MCF-7 cells efficiently through the FA receptor-mediated endocytosis. DOX@FA-SPIONs were tested in nude mice with xenograft MCF-7 breast tumor though tail intravenous injection and were found inhibiting tumor growth more efficiently. The application of a magnetic field (MF) greatly improved the growth inhibiting efficiencies of DOX@FA-SPIONs on MCF-7 cells in vitro and on xenograft MCF-7 breast tumor of nude mice in vivo. The aggregation of SPIONs in tumor was monitored by magnetic resonance imaging (MRI) as the DOX@FA-SPIONs exhibited high r(2) relaxivity (81:77 mM(-1)S(-1)). Histology on liver, Lung, kidney and heart in mice showed no significant toxicity of DOX@ FA-SPIONs on mice organs after 35-day treatment The FA-SPIONs area high efficient drug delivery nanoplatform for advanced cancer theranostics. (C) 2016 Elsevier B.V. All rights reserved.