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Polyglycerol Grafting Shields Nanoparticles from Protein Corona Formation to Avoid Macrophage Uptake.
ACS Nano ( IF 15.8 ) Pub Date : 2020-05-07 , DOI: 10.1021/acsnano.0c02289 Yajuan Zou , Shinji Ito , Fumi Yoshino 1 , Yuta Suzuki , Li Zhao 2 , Naoki Komatsu
ACS Nano ( IF 15.8 ) Pub Date : 2020-05-07 , DOI: 10.1021/acsnano.0c02289 Yajuan Zou , Shinji Ito , Fumi Yoshino 1 , Yuta Suzuki , Li Zhao 2 , Naoki Komatsu
Affiliation
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Upon contact with biofluids, proteins are quickly adsorbed onto the nanoparticle (NP) surface to form a protein corona, which initiates the opsonization and facilitates the rapid clearance of the NP by macrophage uptake. Although polyethylene glycol (PEG) functionalization has been the standard approach to evade macrophage uptake by reducing protein adsorption, it cannot fully eliminate nonspecific uptake. Herein, polyglycerol (PG) grafting is demonstrated as a better alternative to PEG. NPs of various size and material were grafted with PG and PEG at 30, 20, and 10 wt % contents by controlling the reaction conditions, and the resulting NP-PG and NP-PEG were characterized qualitatively by IR spectroscopy and quantitatively by thermogravimetric analysis. Their resistivity to adsorption of the proteins in fetal bovine serum and human plasma were compared by polyacrylamide gel electrophoresis, bicinchoninic acid assay, and liquid chromatography-tandem mass spectrometry, giving a consistent conclusion that PG shields protein adsorption more efficiently than does PEG. The macrophage uptake was assayed by transmission electron microscopy and by extinction spectroscopy or inductively coupled plasma mass spectrometry, revealing that PG avoids macrophage uptake more efficiently than does PEG. In particular, a NP coated with PG at 30 wt % (NP-PG-h) prevents corona formation almost completely, regardless of NP size and core material, leading to the complete evasion of macrophage uptake. Our findings demonstrate that PG grafting is a promising strategy in nanomedicine to improve anti-biofouling property and stealth efficiency in nanoformulations.
中文翻译：
聚甘油接枝可屏蔽蛋白质电晕形成过程中的纳米颗粒，避免巨噬细胞摄取。
与生物流体接触后，蛋白质会迅速吸附到纳米颗粒（NP）表面上，形成蛋白质电晕，从而引发调理作用，并通过巨噬细胞摄取促进NP的快速清除。尽管聚乙二醇（PEG）功能化已成为通过减少蛋白质吸附来逃避巨噬细胞摄取的标准方法，但它无法完全消除非特异性摄取。本文中，聚甘油（PG）接枝被证明是PEG的更好替代品。通过控制反应条件，将各种尺寸和材料的NP分别以30、20和10 wt％的含量接枝PG和PEG，然后通过IR光谱对所得NP-PG和NP-PEG进行定性表征，并通过热重分析进行定量表征。通过聚丙烯酰胺凝胶电泳，比辛可宁酸测定和液相色谱-串联质谱法比较了它们对胎牛血清和人血浆中蛋白质吸附的抵抗力，得出了一个一致的结论，即PG比PEG更有效地屏蔽了蛋白质吸附。通过透射电子显微镜和消光光谱或电感耦合等离子体质谱法分析了巨噬细胞的摄取，揭示了PG比PEG更有效地避免了巨噬细胞的摄取。特别是，NP涂有30 wt％的PG（NP-PG- 通过透射电子显微镜和消光光谱或电感耦合等离子体质谱法分析了巨噬细胞的摄取，揭示了PG比PEG更有效地避免了巨噬细胞的摄取。特别是，NP涂有30 wt％的PG（NP-PG- 通过透射电子显微镜和消光光谱或电感耦合等离子体质谱法分析了巨噬细胞的摄取，揭示了PG比PEG更有效地避免了巨噬细胞的摄取。特别是，NP涂有30 wt％的PG（NP-PG-h）几乎完全防止了电晕的形成，而与NP的大小和核心材料无关，从而完全逃避了巨噬细胞的吸收。我们的发现表明，PG接枝是提高纳米制剂抗生物结垢性能和隐身效率的纳米药物的一种有前途的策略。
更新日期：2020-06-23
中文翻译：
聚甘油接枝可屏蔽蛋白质电晕形成过程中的纳米颗粒，避免巨噬细胞摄取。
与生物流体接触后，蛋白质会迅速吸附到纳米颗粒（NP）表面上，形成蛋白质电晕，从而引发调理作用，并通过巨噬细胞摄取促进NP的快速清除。尽管聚乙二醇（PEG）功能化已成为通过减少蛋白质吸附来逃避巨噬细胞摄取的标准方法，但它无法完全消除非特异性摄取。本文中，聚甘油（PG）接枝被证明是PEG的更好替代品。通过控制反应条件，将各种尺寸和材料的NP分别以30、20和10 wt％的含量接枝PG和PEG，然后通过IR光谱对所得NP-PG和NP-PEG进行定性表征，并通过热重分析进行定量表征。通过聚丙烯酰胺凝胶电泳，比辛可宁酸测定和液相色谱-串联质谱法比较了它们对胎牛血清和人血浆中蛋白质吸附的抵抗力，得出了一个一致的结论，即PG比PEG更有效地屏蔽了蛋白质吸附。通过透射电子显微镜和消光光谱或电感耦合等离子体质谱法分析了巨噬细胞的摄取，揭示了PG比PEG更有效地避免了巨噬细胞的摄取。特别是，NP涂有30 wt％的PG（NP-PG- 通过透射电子显微镜和消光光谱或电感耦合等离子体质谱法分析了巨噬细胞的摄取，揭示了PG比PEG更有效地避免了巨噬细胞的摄取。特别是，NP涂有30 wt％的PG（NP-PG- 通过透射电子显微镜和消光光谱或电感耦合等离子体质谱法分析了巨噬细胞的摄取，揭示了PG比PEG更有效地避免了巨噬细胞的摄取。特别是，NP涂有30 wt％的PG（NP-PG-h）几乎完全防止了电晕的形成，而与NP的大小和核心材料无关，从而完全逃避了巨噬细胞的吸收。我们的发现表明，PG接枝是提高纳米制剂抗生物结垢性能和隐身效率的纳米药物的一种有前途的策略。
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