Lin Jia-Jyun, Chen Jenn-Shing, Huang Shih-Jer, Ko Jyun-Han, Wang Yu-Ming, Chen Ting-Lung, Wang Li-Fang
Department of Life Science, National University of Kaohsiung, Kaohsiung City 811, Taiwan.
Biomaterials. 2009 Oct;30(28):5114-24. doi: 10.1016/j.biomaterials.2009.06.004. Epub 2009 Jun 26.
Superparamagnetic iron oxides possess specific magnetic properties in the presence of an external magnetic field, which make them an attractive platform as contrast agents for magnetic resonance imaging (MRI) and as carriers for drug delivery. In this study, we investigate the drug delivery and the MRI properties of folate-mediated water-soluble iron oxide incorporated into micelles. Pluronic F127 (PF127), which can be self-assembled into micelles upon increasing concentration or raising temperatures, is used to decorate water-soluble polyacrylic acid-bound iron oxides (PAAIO) via a chemical reaction. Next, the hydrophobic dye Nile red is encapsulated into the hydrophobic poly(propylene oxide) compartment of PF127 as a model drug and as a fluorescent agent. Upon encapsulation, PAAIO retains its superparamagnetic characteristics, and thus can be used for MR imaging. A tumor-specific targeting ligand, folic acid (FA), is conjugated onto PF127-PAAIO to produce a multifunctional superparamagnetic iron oxide, FA-PF127-PAAIO. FA-PF127-PAAIO can be simultaneously applied as a diagnostic and therapeutic agent that specifically targets cancer cells that overexpress folate receptors in their cell membranes. PF127-PAAIO is used as a reference group. Based on FTIR and UV-vis absorbance spectra, the successful synthesis of PF127-PAAIO and FA-PF127-PAAIO is realized. The magnetic nanoparticle clusters of PF127-PAAIO and FA-PF127-PAAIO are visualized by transmission electron microscope (TEM). FA-PF127-PAAIO, together with a targeting ligand, displays a higher intracellular uptake into KB cells. This result is confirmed by laser confocal scanning microscopy (CLSM), flow cytometry, and atomic absorption spectroscopy (AAS) studies. The hysteresis curves, generated by using a superconducting quantum interference device (SQUID) magnetometer analysis, demonstrate that the magnetic nanoparticles are superparamagnetic with insignificant hysteresis. The MTT assay explains the negligible cell cytotoxicity of PF127-PAAIO and FA-PF127-PAAIO. In KB cells, the in vitro MRI study indicates the better T(2)-weighted images in FA-PF127-PAAIO than in PF127-PAAIO.
超顺磁性氧化铁在外部磁场存在时具有特定的磁性，这使其成为磁共振成像（MRI）造影剂和药物递送载体的有吸引力的平台。在本研究中，我们研究了叶酸介导的水溶性氧化铁掺入胶束后的药物递送和MRI特性。普朗尼克F127（PF127）在浓度增加或温度升高时可自组装成胶束，通过化学反应用于修饰水溶性聚丙烯酸结合的氧化铁（PAAIO）。接下来，将疏水性染料尼罗红封装到PF127的疏水性聚环氧丙烷隔室中作为模型药物和荧光剂。封装后，PAAIO保留其超顺磁性特性，因此可用于MR成像。肿瘤特异性靶向配体叶酸（FA）与PF127-PAAIO共轭，以产生多功能超顺磁性氧化铁FA-PF127-PAAIO。FA-PF127-PAAIO可同时用作诊断和治疗剂，特异性靶向细胞膜上过表达叶酸受体的癌细胞。PF127-PAAIO用作参考组。基于傅里叶变换红外光谱（FTIR）和紫外可见吸收光谱，实现了PF127-PAAIO和FA-PF127-PAAIO的成功合成。通过透射电子显微镜（TEM）观察到PF127-PAAIO和FA-PF127-PAAIO的磁性纳米颗粒簇。FA-PF127-PAAIO与靶向配体一起，在KB细胞中显示出更高的细胞内摄取。激光共聚焦扫描显微镜（CLSM）、流式细胞术和原子吸收光谱（AAS）研究证实了这一结果。使用超导量子干涉装置（SQUID）磁力计分析生成的磁滞回线表明，磁性纳米颗粒具有超顺磁性，磁滞可忽略不计。MTT法解释了PF127-PAAIO和FA-PF127-PAAIO可忽略不计的细胞毒性。在KB细胞中，体外MRI研究表明，FA-PF127-PAAIO的T2加权图像比PF127-PAAIO的更好。
