CAJ | 학술논문

背景：超顺磁四氧化三铁纳米粒子(Fe 3 O 4 NPs)被广泛应用于MRI成像，为防止其聚集和实现高精度肿瘤诊断，制备高度稳定性、生物相容性和肿瘤靶向性的超顺磁MRI对比剂至关重要。目的：合成具有基于叶酸受体靶向的肿瘤靶向性双亲性超顺磁复合粒子。方法：首先通过化学共沉淀法制备出Fe 3 O 4 NPs，再用N，N’-二环己基碳二亚胺作脱水剂，通过酯键将双亲性高分子Pluronic-F127(PF127)与叶酸(FA)分子连接，从而形成PF127-FA偶联物，最后用PF127-FA包裹Fe 3 O 4纳米粒子，形成稳定的具有肿瘤靶向功能的双亲性超顺磁复合粒子。分别采用透射电镜、傅里叶红外光谱、紫外可见吸收光谱、热重分析、振动样品磁强计和T2加权成像对其进行表征，通过细胞毒性实验初步表征其细胞毒性。结果与结论：通过酯化反应制备了Pluronic-F127与FA偶联物，再用其包裹Fe 3O4纳米粒子，成功制备出具有良好水溶性和生物相容性的超顺磁性复合粒子。该PF127-FA-Fe 3 O 4复合粒子透射电镜观察到该复合粒子大部分粒径小于200 nm， Fe 3 O 4核心大小为10-20 nm，傅里叶红外光谱和紫外可见吸收光谱结果证明了叶酸被成功修饰到超顺磁性复合粒子表面。热重分析结果表明PF127-FA占PF127-FA-Fe 3 O 4复合粒子总量的27.2 wt%。磁性检测结果表明该复合粒子饱和磁强度Ms为47.35 emu/g，核磁共振仪成像测得其弛豫率为0.025×106 mol/s。细胞毒性实验表明显示了可以忽略的毒性。因此，实验成功制备了可用于肿瘤靶向性MRI对比剂的双亲性超顺磁复合物，实验所制备的PF127-FA-Fe 3 O 4复合粒子有望用于肿瘤靶向性MRI对比剂。
배경：초순자사양화삼철납미입자(Fe 3 O 4 NPs)피엄범응용우MRI성상，위방지기취집화실현고정도종류진단，제비고도은정성、생물상용성화종류파향성적초순자MRI대비제지관중요。목적：합성구유기우협산수체파향적종류파향성쌍친성초순자복합입자。방법：수선통과화학공침정법제비출Fe 3 O 4 NPs，재용N，N’-이배기기탄이아알작탈수제，통과지건장쌍친성고분자Pluronic-F127(PF127)여협산(FA)분자련접，종이형성PF127-FA우련물，최후용PF127-FA포과Fe 3 O 4납미입자，형성은정적구유종류파향공능적쌍친성초순자복합입자。분별채용투사전경、부리협홍외광보、자외가견흡수광보、열중분석、진동양품자강계화T2가권성상대기진행표정，통과세포독성실험초보표정기세포독성。결과여결론：통과지화반응제비료Pluronic-F127여FA우련물，재용기포과Fe 3O4납미입자，성공제비출구유량호수용성화생물상용성적초순자성복합입자。해PF127-FA-Fe 3 O 4복합입자투사전경관찰도해복합입자대부분립경소우200 nm， Fe 3 O 4핵심대소위10-20 nm，부리협홍외광보화자외가견흡수광보결과증명료협산피성공수식도초순자성복합입자표면。열중분석결과표명PF127-FA점PF127-FA-Fe 3 O 4복합입자총량적27.2 wt%。자성검측결과표명해복합입자포화자강도Ms위47.35 emu/g，핵자공진의성상측득기이예솔위0.025×106 mol/s。세포독성실험표명현시료가이홀략적독성。인차，실험성공제비료가용우종류파향성MRI대비제적쌍친성초순자복합물，실험소제비적PF127-FA-Fe 3 O 4복합입자유망용우종류파향성MRI대비제。
BACKGROUND:Superparamagnetic iron oxide nanoparticles (Fe3O4 NPs) have been widely used in MRI. It is vital to prepare the superparamagnetic MRI contrast agent with high stability, biocompatibility and tumor targeting in order to prevent the aggregation of Fe 3 O 4 NPs and realize the high-precision diagnose of tumor. OBJECTIVE:To prepare the amphiphilic superparamagnetic composite particles with tumor targeting mediated by folate receptor. METHODS:The stable amphiphilic superparamagnetic composite particles with tumor targeting function were prepared by coating the Fe3O4 NPs with a Pluronic F127-folic acid conjugate, which was synthesized via an esterification reaction between the carboxyl group of the tumor targeting molecule, folic acid and the hydroxyl group of an amphiphilic triblock copolymer, Pluronic F127. The resultant Pluronic F127-folic acid-Fe3O4 composite particles were characterized by transmission electron microscopy, Fourier transform infrared-spectra, UV-vis absorption spectra, thermal gravimetric analysis, vibrating sample magnetometer and T2-weighted imaging. WST assay was used to characterize their cytotoxicity preliminarily. RESULTS AND CONCLUSION:The Pluronic F127-folic acid conjugates were prepared via esterification reaction. Then Fe 3 O 4 NPs were wrapped with Pluronic F127-folic acid to result in the superparamagnetic composite particles with wel dispersion and biocompatibility. The size of most superparamagnetic composite particles was less than 200 nm and the size of Fe 3 O 4 core was 10-20 nm from the observation of transmission electron microscopy. The results from the Fourier transform infrared-spectra and UV-vis absorption spectroscop confirmed that folic acid molecules were modified on the surface of the superparamagnetic composite particles successful y. The mass ratio of Pluronic F127-folic acid conjugate was determined by thermal gravimetric analysis as 27.2 wt%in the resultant Pluronic F127-folic acid-Fe 3 O 4 composite particles. The saturated magnetic intensity of the superparamagnetic composite particles was 47.35 emu/g by vibrating sample magnetometer and the relaxation rate was 0.025×106 mol/s from MRI. The WST assay showed the negligible cellcytotoxicity of Pluronic F127-folic acid-Fe3O4. The superparamagnetic composite particles have potential application as the MRI contrast agents with tumor targeting, and the Pluronic F127-folic acid-Fe 3 O 4 composite particles is expected to be used as a MRI contrast agent for tumor targeting.