Probing the Role of Charged Functional Groups on Nanoparticles Grafted with Polyglycerol in Protein Adsorption and Cellular Uptake
Probing the Role of Charged Functional Groups on Nanoparticles Grafted with Polyglycerol in Protein Adsorption and Cellular Uptake
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DOI：
10.1002/adfm.202111077
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发表时间：
2022-01
影响因子：
19
通讯作者：
Y. Zou;S. Ito;M. Fujiwara;N. Komatsu
中科院分区：
文献类型：
--
作者：
Y. Zou;S. Ito;M. Fujiwara;N. Komatsu
在生物流体中，纳米颗粒（NPs）表面的带电官能团通过蛋白质冠与细胞相互作用。然而，级联效应的带电基团对电晕形成和细胞吸收仍然不清楚。在本文中，在聚甘油（PG）接枝的纳米金刚石和超顺磁性氧化铁NP的外围定量引入羧基、硫酸根和氨基，以探测它们在冠形成和细胞摄取中的作用。NP的摄取效率和细胞内聚集状态被揭示与带电基团的蛋白质亲和力相关;较低密度的硫酸盐和羧酸盐对蛋白质没有亲和力，诱导可忽略的或没有细胞摄取。相比之下，硫酸盐在较高的密度和铵与胎牛血清蛋白改变聚集状态的内化纳米粒子。进一步证明，NP-PG-OSO 3-和NP-PG-NH3+表面上不同的蛋白质冠分布决定了它们的吸收机制。NP-PG-OSO 3-的蛋白质冠通过下调巨胞饮和网格蛋白介导的内吞作用抑制细胞摄取，而NP-PG-NH3+的蛋白质冠通过上调巨胞饮和小窝介导的内吞作用增强摄取。这项研究阐明了蛋白质吸附和细胞摄取中带电基团的难以捉摸的作用，这揭示了纳米医学中控制细胞摄取和治疗诊断学的NP设计。
In biofluids, charged functional groups on the surface of nanoparticles (NPs) interact with cells through the protein corona. However, the cascade effects of charged groups on corona formation and cellular uptake remain unclear. Herein, carboxy, sulfate, and amino groups are quantitatively introduced at the periphery of polyglycerol (PG)‐grafted nanodiamond and superparamagnetic iron oxide NP to probe their roles in corona formation and cellular uptake. The uptake efficiency and intracellular aggregation state of NPs are revealed to correlate with protein affinity of the charged groups; sulfate at lower density and carboxylate exhibit no affinity to proteins, inducing negligible or no cellular uptake. In contrast, sulfate at higher density and ammonium associate with fetal bovine serum proteins to alter the aggregation state of the internalized NPs. It is further demonstrated that the distinct protein corona profiles on NP‐PG‐OSO3− and NP‐PG‐NH3+ surfaces dictate their uptake mechanism. The protein corona of NP‐PG‐OSO3− suppresses cellular uptake via downregulation of macropinocytosis and clathrin‐mediated endocytosis, whereas that of NP‐PG‐NH3+ enhances uptake through upregulation of macropinocytosis and caveolae‐mediated endocytosis. This study clarifies the elusive role of the charged groups in protein adsorption and cellular uptake, which sheds light on NP design for controlled cellular uptake and theranostics in nanomedicine.