Engineering Poly(ethylene glycol) Particles for Improved Biodistribution
Engineering Poly(ethylene glycol) Particles for Improved Biodistribution
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DOI：
10.1021/nn5061578
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发表时间：
2015-02-01
期刊：
影响因子：
17.1
通讯作者：
Caruso, Frank
中科院分区：
文献类型：
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作者：
Cui, Jiwei;De Rose, Robert;Caruso, Frank
我们报道了用介孔二氧化硅(MS)模板法通过调节聚乙二醇水凝胶的相对分子质量、颗粒大小和模板的存在与否来制备聚乙二醇水凝胶颗粒，并研究了这些颗粒的细胞结合和生物分布。介绍了一种基于人全血的体外循环行为预测方法，该方法比传统的基于细胞系的体外循环行为预测方法更灵敏、更具相关性。MS@PEG颗粒(模板存在)与粒细胞和单核细胞的关联性高于聚乙二醇颗粒(模板不存在)。增加聚乙二醇的相对分子质量(从10 kDa到40 kDa)或减小聚乙二醇颗粒的大小(从1400到150 nm)会减少聚乙二醇颗粒的吞噬血细胞结合。小鼠体内分布研究表明，与MS@PEG颗粒相比，聚乙二醇颗粒的循环时间延长(>；12h)，较小的聚乙二醇颗粒(150 Nm)在血液中的滞留时间(>；400 nm)在注射后12小时至少增加了4倍。我们的发现突出了聚合物水凝胶颗粒的独特方面对生物相互作用的影响。已报道的聚乙二醇水凝胶颗粒代表了一类具有潜在生物医学应用的新型聚合物载体。
We report the engineering of poly(ethylene glycol) (PEG) hydrogel particles using a mesoporous silica (MS) templating method via tuning the PEG molecular weight, particle size, and the presence or absence of the template and investigate the cell association and biodistribution of these particles. An ex vivo assay based on human whole blood that is more sensitive and relevant than traditional cell-line based assays for predicting in vivo circulation behavior is introduced. The association of MS@PEG particles (template present) with granulocytes and monocytes is higher compared with PEG particles (template absent). Increasing the PEG molecular weight (from 10 to 40 kDa) or decreasing the PEG particle size (from 1400 to 150 nm) reduces phagocytic blood cell association of the PEG particles. Mice biodistribution studies show that the PEG particles exhibit extended circulation times (>12 h) compared with the MS@PEG particles and that the retention of smaller PEG particles (150 nm) in blood, when compared with larger PEG particles (>400 nm), is increased at least 4-fold at 12 h after injection. Our findings highlight the influence of unique aspects of polymer hydrogel particles on biological interactions. The reported PEG hydrogel particles represent a new class of polymer carriers with potential biomedical applications.