Folic acid-Pluronic F127 magnetic nanoparticle clusters for combined targeting, diagnosis, and therapy applications
Folic acid-Pluronic F127 magnetic nanoparticle clusters for combined targeting, diagnosis, and therapy applications
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DOI：
10.1016/j.biomaterials.2009.06.004
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发表时间：
2009-10-01
期刊：
影响因子：
14
通讯作者：
Wang, Li-Fang
中科院分区：
文献类型：
--
作者：
Lin, Jia-Jyun;Chen, Jenn-Shing;Wang, Li-Fang
超顺磁性氧化铁在外部磁场的存在下具有特定的磁性，这使得它们成为磁共振成像（MRI）造影剂和药物递送载体的有吸引力的平台。在这项研究中，我们研究了叶酸介导的水溶性氧化铁纳入胶束的药物输送和MRI性能。Pluronic（R）F127（PF 127）可以在增加浓度或升高温度时自组装成胶束，用于通过化学反应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作为模型药物和荧光剂包封到PF 127的疏水性聚（环氧丙烷）隔室中。封装后，PAAIO保留其超顺磁性特征，因此可用于MR成像。将肿瘤特异性靶向配体叶酸（FA）缀合到PF 127-PAA 10上以产生多功能超顺磁性氧化铁FA-PF 127-PAA 10。FA-PF 127-PAA 10可以同时用作诊断和治疗剂，其特异性靶向在其细胞膜中过表达叶酸受体的癌细胞。PF 127-PAA 10用作参考组。通过红外光谱和紫外-可见吸收光谱的分析，成功合成了PF 127-PAAIO和FA-PF 127-PAAIO。通过透射电子显微镜（TEM）观察PF 127-PAA 10和FA-PF 127-PAA 10的磁性纳米颗粒簇。FA-PF 127-PAA 10与靶向配体一起显示出更高的KB细胞内摄取。这一结果通过激光共聚焦扫描显微镜（CLSM）、流式细胞术和原子吸收光谱（AAS）研究得到证实。磁滞曲线，通过使用超导量子干涉仪（SQUID）磁强计分析，表明磁性纳米粒子是超顺磁性与微不足道的磁滞。MITT测定解释了PF 127-PAA 10和FA-PF 127-PAA 10的细胞毒性可忽略不计。在KB细胞中，体外MRI研究表明FA-PF 127-PAA 10中的T-2加权图像优于PF 127-PAA 10。(C)2009爱思唯尔有限公司保留所有权利。
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 (R) 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 MITT 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. (C) 2009 Elsevier Ltd. All rights reserved.