The Impact of Protein Corona Formation on the Macrophage Cellular Uptake and Biodistribution of Spherical Nucleic Acids.
The Impact of Protein Corona Formation on the Macrophage Cellular Uptake and Biodistribution of Spherical Nucleic Acids.
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DOI：
10.1002/smll.201603847
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发表时间：
2017-04
期刊：
影响因子：
--
通讯作者：
Mirkin CA
中科院分区：
文献类型：
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作者：
Chinen AB;Guan CM;Ko CH;Mirkin CA
研究了血清蛋白吸附对球形核酸（SNAs）生物命运的影响。通过蛋白质组学分析，它表明，G-四链体模板上的金纳米粒子的表面上的SNA的形式介导的蛋白质冠的形成，这是丰富的补体蛋白相对于SNA组成的聚胸腺嘧啶（聚T）DNA。细胞摄取研究表明，巨噬细胞上的补体受体识别SNA蛋白质冠，促进其内化，并导致富含G的SNA在肝脏和脾脏中比体内多聚T SNA更多地积累。这些结果支持核酸序列和结构可以介导纳米颗粒-生物分子相互作用并改变其细胞摄取和生物分布性质的结论，并说明核酸序列是SNA治疗剂设计中的重要参数。
The effect of serum protein adsorption on the biological fate of Spherical Nucleic Acids (SNAs) is investigated. Through a proteomic analysis, it is shown that G-quadruplexes templated on the surface of a gold nanoparticle in the form of SNAs mediate the formation of a protein corona that is rich in complement proteins relative to SNAs composed of poly-thymine (poly-T) DNA. Cellular uptake studies show that complement receptors on macrophage cells recognize the SNA protein corona, facilitating their internalization, and causing G-rich SNAs to accumulate in the liver and spleen more than poly-T SNAs in vivo. These results support the conclusion that nucleic acid sequence and architecture can mediate nanoparticle—biomolecule interactions and alter their cellular uptake and biodistribution properties and illustrate that nucleic acid sequence is an important parameter in the design of SNA therapeutics.