摘要
目的制备具有良好叶酸受体肿瘤靶向且性质稳定超顺磁氧化铁纳米粒并评价其叶酸受体肿瘤靶向性。方法采用"三步法"合成叶酸-羧甲基壳聚糖超顺磁氧化铁纳米粒(folic acid-O-carboxymethylchitosan-superparamagnetic iron ox-ide nanoparticle,FA-OCMCS-SPIO-NPs):共沉淀法合成超顺磁氧化铁纳米粒后,依次用羧甲基壳聚糖和叶酸对纳米粒表面进行共价修饰。应用透射电镜、激光散射粒度分析仪和电位测定仪、X-Ray衍射法、傅立叶红外、超导电子干涉等对中间产物及终产物进行表征。菲洛嗪法和普鲁士蓝染色评价叶酸-羧甲基壳聚糖超顺磁氧化铁纳米粒的叶酸受体肿瘤靶向性。结果 X-Ray衍射法表明所有纳米粒粉末的晶型与标准Fe3O4一致,傅立叶红外结果表明叶酸-羧甲基壳聚糖已成功嫁接到超顺磁氧化铁纳米粒,透射电镜结果示纳米粒大多呈圆形或椭圆形,粒径均小于20 nm,激光散射粒度分析仪和电位测定仪叶酸-羧甲基壳聚糖超顺磁氧化铁纳米粒强均粒径为(41.4±0.132)nm、Zeta电位为(-21.36±1.15)mV,超导电子干涉结果示OCMCS和叶酸共价修饰会使得SPIO-NPs的磁性下降,但依然保持强超顺磁性,菲洛嗪法和普鲁士蓝染色表明叶酸-羧甲基壳聚糖超顺磁氧化铁纳米粒具有良好的叶酸受体肿瘤靶向性,靶向性的强度与细胞表面受体数量呈正相关。结论本研究成功合成了超顺磁性强,粒径小,叶酸受体靶向性强的超顺磁氧化铁纳米粒,为其开发用于肿瘤的MRI诊断及治疗奠定基础。
OBJECTIVE To improve superparamagnetic iron oxide nanoparticles （SPIO-NP） stability, biocompatibility and tumor- targeting and evaluate their tumor targeting in vitro. METHODS The folic acid-carboxymethylchitosan-superparamagnetic iron oxide nanoparticles （FA-OCMCS-SPIO-NPs） were synthesized by ＂three-steps＂： at first, superparamagnetic oxide iron nanoparticles were syn- thesized by coprecipitation, then, O-carboxymethyl chitosan and folic acid were successfully immobilized on the surface of SPIO-NPs in turn. The fourier transform infrared spectroscopy , X-Ray diffraction were used to confirm their synthesis, meanwhile, transmission elec- tron microscope （TEM）, dynamic light scattering （DIS）, Zeta-potential measurement and vibrating sample magnetometry （VSM） were applied to characterize their physicochemical properies. Ferrozine assay and Prussian blue staining were used to evaluate their tumor tar- geting in vitro. RESULTS X-Ray diffraction showed the crystalline powder of FA-CMCS-SPIO-NPs agree with the standard Fe304＇s, Fourier transform infrared results showed O-carboxymethylchitosan and folic acid were covalently modified on the surface of SPIO-NPs suc- cessfully, TEM showed all synthesized SPIO-NPs were almost spherical or ellipsoidal. Their sizes were less then 20 nm, dynamic light scattering （DLS）, Zeta-potential results demonstrate the intensity particle size distributions of FA-OCMCS-SPIO-NPs were （41.4± 0. 132）nm, Zeta potential were （ -21.36 ± 1.15）mV. The surface modification may lead to decrese of magnetisms Ferrozine assay and Prussian blue staining results showed FA-OCMCS-SPIO-NPs had good tumor targeting and the tumor targeting had good relations with the a- mount of FR on surface of tumor cells. CONCLUSION FA-OCMCS-SPIO-NPs with strong superparamagnetic property, excellent stability, and good folate receptor targeting is successfully synthesized, which demonstrated the potential for tumor MRI diagnose and therapy.
出处
《中国药学杂志》
CAS
CSCD
北大核心
2012年第18期1483-1488,共6页
Chinese Pharmaceutical Journal
基金
广东省自然科学基金博士启动项目(S2011040003279)
韶关市科学计划项目韶科(卫)2011-20
韶关市卫生局项目(Y11029)
关键词
叶酸
羧甲基壳聚糖
超顺次氧化铁纳米粒
肿瘤靶向
folic acid
O-carboxymethylchitosan
superparamagnetic iron oxide nanoparticles
tumor targeting
