Polyethylene glycol modified, cross-linked starch-coated iron oxide nanoparticles for enhanced magnetic tumor targeting.
Polyethylene glycol modified, cross-linked starch-coated iron oxide nanoparticles for enhanced magnetic tumor targeting.
复制标题
聚乙烯乙二醇改性，交联的淀粉氧化铁纳米颗粒可增强磁性肿瘤的靶向。
DOI：
10.1016/j.biomaterials.2010.11.040
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发表时间：
2011-03
期刊：
影响因子：
14
通讯作者：
Yang, Victor C.
中科院分区：
文献类型：
--
作者：
Cole, Adam J.;David, Allan E.;Wang, Jianxin;Galban, Craig J.;Hill, Hannah L.;Yang, Victor C.
关键词：
虽然已经在许多模型中实现了氧化铁纳米颗粒的成功的磁性肿瘤靶向，但是网状内皮系统（RES）对磁性合适颗粒的快速血液清除限制了它们用于靶向的可用性。这项工作旨在开发一种长循环磁性氧化铁纳米颗粒（MNP）平台，能够通过循环持续暴露于肿瘤，从而增强磁性肿瘤靶向。使用简单的N-羟基琥珀酰亚胺（NHS）化学方法，用5 kDa（A5，D5）或20 kDa（A20，D20）聚乙二醇（PEG）链成功修饰了胺化、交联淀粉（DN）和氨基硅烷（A）涂覆的MNP，并进行了表征。平台（A5和D5、A20和D20）之间相同的PEG重量类似物在尺寸（140-190 nm）和相对PEG标记（1.5%的表面胺- A5/D5、0.4% - A20/D20）方面相似，所有PEG-MNP都具有适合于磁性靶向的磁化性质。在体外RES模拟中研究候选PEG-MNP以预测长循环特征。D5和D20表现最佳，显示出在37°C下在细胞培养基中的持续尺寸稳定性，并且与先前靶向的未修饰的淀粉MNP相比，RAW 264.7巨噬细胞中的摄取低7（D20）至10（D5）倍（D）。体外观察结果在体内得到验证，D5（7.29小时）和D20（11.75小时）的半衰期远长于D（0.12小时）。如通过血浆AUC 0-∞测量的，改善的血浆稳定性使肿瘤MNP暴露增强100（D5）至150（D20）倍。使用磁共振成像（MRI）在9 L-神经胶质瘤大鼠模型（12 mg Fe/kg）中目视确认24小时内的持续肿瘤暴露。研究结果表明，D5和D20都是有前途的MNP平台，用于增强磁性肿瘤靶向，从而促进在肿瘤模型中的进一步研究。
While successful magnetic tumor targeting of iron oxide nanoparticles has been achieved in a number of models, the rapid blood clearance of magnetically suitable particles by the reticuloendothelial system (RES) limits their availability for targeting. This work aimed to develop a long-circulating magnetic iron oxide nanoparticle (MNP) platform capable of sustained tumor exposure via the circulation and, thus, enhanced magnetic tumor targeting. Aminated, cross-linked starch (DN) and aminosilane (A) coated MNPs were successfully modified with 5 kDa (A5, D5) or 20 kDa (A20, D20) polyethylene glycol (PEG) chains using simple N-Hydroxysuccinimide (NHS) chemistry and characterized. Identical PEG-weight analogues between platforms (A5 & D5, A20 & D20) were similar in size (140–190 nm) and relative PEG labeling (1.5% of surface amines – A5/D5, 0.4% – A20/D20), with all PEG-MNPs possessing magnetization properties suitable for magnetic targeting. Candidate PEG-MNPs were studied in RES simulations in vitro to predict long-circulating character. D5 and D20 performed best showing sustained size stability in cell culture medium at 37°C and 7 (D20) to 10 (D5) fold less uptake in RAW264.7 macrophages when compared to previously targeted, unmodified starch MNPs (D). Observations in vitro were validated in vivo, with D5 (7.29 hr) and D20 (11.75 hr) showing much longer half-lives than D (0.12 hr). Improved plasma stability enhanced tumor MNP exposure 100 (D5) to 150 (D20) fold as measured by plasma AUC0-∞ Sustained tumor exposure over 24 hours was visually confirmed in a 9L-glioma rat model (12 mg Fe/kg) using magnetic resonance imaging (MRI). Findings indicate that both D5 and D20 are promising MNP platforms for enhanced magnetic tumor targeting, warranting further study in tumor models.
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