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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 prepare tumor-targeted and stable superparamagnetic iron oxide nanoparticles with good folate receptor and to evaluate their tumor targeting of folate receptor. Methods The folic acid-O-carboxymethylchitosan-superparamagnetic iron ox-ide nanoparticle (FA-OCMCS-SPIO-NPs) After the synthesis of superparamagnetic iron oxide nanoparticles by precipitation method, the surface of nanoparticles was covalently modified with carboxymethyl chitosan and folic acid. The intermediates and final products were characterized by transmission electron microscopy, laser scattering particle size analyzer and potentiometer, X-Ray diffraction, Fourier transform infrared (FTIR) and superconducting electron interference. Evaluation of Folic Acid-Carboxymethyl Chitosan Superparamagnetic Iron Oxide Nanoparticles on Folate Receptor Tumor Targets by Phenazine and Prussian Blue Staining. Results X-Ray diffraction showed that all the nanoparticle powders had the same crystal form as the standard Fe3O4. Fourier transform infrared spectroscopy showed that folic acid-carboxymethyl chitosan had been successfully grafted onto the superparamagnetic iron oxide nanoparticles. Transmission electron microscopy showed that most of the nanoparticles (41.4 ± 0.132) nm, and the diameter of the particles was less than 20 nm. The average particle diameter of the superparamagnetic nanoparticles of folate-carboxymethylated chitosan was (41.4 ± 0.132) nm by laser light scattering particle size analyzer and potentiometer, Zeta potential was (-21.36 ± 1.15) mV. The result of the superconducting electron interference showed that the co-modification of OCMCS and folic acid could decrease the magnetic properties of SPIO-NPs, but still maintain the superparamagnetism. - Carboxymethyl chitosan superparamagnetic iron oxide nanoparticles have good folate receptor tumor targeting, and the intensity of the targeting is positively correlated with the number of cell surface receptors. Conclusions This study successfully synthesized superparamagnetic iron oxide nanoparticles with strong superparamagnetism, small particle size and strong folate receptor targeting, which laid the foundation for the development of MRI diagnosis and treatment of tumors.