Protein adsorption is required for stealth effect of poly(ethylene glycol)- and poly(phosphoester)-coated nanocarriers
Protein adsorption is required for stealth effect of poly(ethylene glycol)- and poly(phosphoester)-coated nanocarriers
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DOI：
10.1038/nnano.2015.330
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发表时间：
2016-04-01
影响因子：
38.3
通讯作者：
Wurm, Frederik R.
中科院分区：
文献类型：
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作者：
Schoettler, Susanne;Becker, Greta;Wurm, Frederik R.
目前减少药物递送载体的非特异性细胞摄取的金标准是通过聚（乙二醇）（PEG）的共价连接。据认为，PEG可以减少蛋白质吸附，从而赋予隐形效果。在这里，我们表明，聚苯乙烯纳米载体，已被修饰与PEG或聚（乙基乙烯磷酸）（PEEP）和暴露于血浆蛋白表现出低细胞摄取，而那些没有暴露于血浆蛋白显示高非特异性摄取。质谱分析显示，暴露的纳米载体形成了一个蛋白质冠，其中含有丰富的簇蛋白（也称为载脂蛋白J）。当聚合物修饰的纳米载体与丛生蛋白一起孵育时，可以减少非特异性细胞摄取。我们的研究结果表明，除了减少蛋白质吸附外，PEG和现在的PEEP还可以影响在纳米载体周围形成的蛋白质冠的组成，并且不同蛋白质的存在对于防止非特异性细胞摄取是必要的。
The current gold standard to reduce non-specific cellular uptake of drug delivery vehicles is by covalent attachment of poly(ethylene glycol) (PEG). It is thought that PEG can reduce protein adsorption and thereby confer a stealth effect. Here, we show that polystyrene nanocarriers that have been modified with PEG or poly(ethyl ethylene phosphate) (PEEP) and exposed to plasma proteins exhibit a low cellular uptake, whereas those not exposed to plasma proteins show high non-specific uptake. Mass spectrometric analysis revealed that exposed nanocarriers formed a protein corona that contains an abundance of clusterin proteins (also known as apolipoprotein J). When the polymer-modified nanocarriers were incubated with clusterin, non-specific cellular uptake could be reduced. Our results show that in addition to reducing protein adsorption, PEG, and now PEEPs, can affect the composition of the protein corona that forms around nanocarriers, and the presence of distinct proteins is necessary to prevent non-specific cellular uptake.