Radiopaque iodinated copolymeric nanoparticles for X-ray imaging applications
Radiopaque iodinated copolymeric nanoparticles for X-ray imaging applications
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DOI：
10.1016/j.biomaterials.2009.06.038
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发表时间：
2009-10-01
期刊：
影响因子：
14
通讯作者：
Margel, Shlomo
中科院分区：
文献类型：
--
作者：
Aviv, Hagit;Bartling, Sonke;Margel, Shlomo
最近，我们描述了用2-甲基丙烯酰氧乙基（2,3,5-三碘苯甲酸酯）（MAOETIB）乳液聚合合成的28.9 +/- 6.3 nm干直径的碘化均聚不透射线纳米颗粒。然而，纳米颗粒在水中的分散不稳定，容易聚集，特别是当分散的纳米颗粒的重量浓度在0.3%以上时。随着纳米颗粒在水相中的浓度升高，团聚率也会增加，从而阻碍了其在体内用作医学x射线成像造影剂的潜力。在这里，我们描述了克服这一限制的努力，通过将单体MAOETIB与低浓度的甲基丙烯酸甘油酯（GMA）乳液共聚，合成了干直径25.5 +/- 4.2 nm的碘化共聚纳米颗粒。所得共聚纳米颗粒的表面亲水性远远优于聚毛etib （PMAOETIB）纳米颗粒。因此，P（MAOETIB-GMA）纳米颗粒在水连续相中具有更强的抗团聚稳定性。在大鼠和小鼠（包括肝癌模型小鼠）静脉注射P（MAOETIB-GMA）纳米颗粒后，ct成像显示注射后30分钟血池可见性显著增强。随后，由于纳米颗粒被网状内皮系统摄取，淋巴结、肝脏和脾脏强烈增强。这有利于癌细胞与健康肝脏组织的分化，并提示我们的颗粒用于肝脏和淋巴结的肿瘤成像。2009爱思唯尔有限公司版权所有。
Recently we described iodinated homopolymeric radiopaque nanoparticles of 28.9 +/- 6.3 nm dry diameter synthesized by emulsion polymerization of 2-methacryloyloxyethyl(2,3,5-triiodobenzoate) (MAOETIB). The nanoparticle aqueous dispersion, however, was not stable and tended to agglomerate, particularly at weight concentration of dispersed nanoparticles above similar to 0.3%. The agglomeration rate increases as the concentration of nanoparticles in aqueous phase rises and prevents the potential in vivo use as contrast agent for medical X-ray imaging. Here we describe efforts to overcome this limitation by synthesis of iodinated copolymeric nanoparticles of 25.5 +/- 4.2 nm dry diameter, by emulsion copolymerization of the monomer, MAOETIB, with a low concentration of glycidyl methacrylate (GMA). The surface of resulting copolymeric nanoparticles is far more hydrophilic than that of polyMAOETIB (PMAOETIB) nanoparticles. Therefore, P(MAOETIB-GMA) nanoparticles are significantly more stable against agglomeration in aqueous continuous phase. After intravenous injection of P(MAOETIB-GMA) nanoparticles in rats and mice (including those with a liver cancer model) CT-imaging revealed a significant enhanced visibility of the blood pool for 30 min after injection. Later, lymph nodes, liver and spleen strongly enhanced due to nanoparticle uptake by the reticuloendothelial system. This favorably enabled the differentiation of cancerous from healthy liver tissue and suggests our particles for tumor imaging in liver and lymph nodes. (C) 2009 Elsevier Ltd. All rights reserved.