Department of Chemical and Biomolecular Engineering, University of California, Berkeley, Berkeley, California, 94720, USA.
Graduate Group in Biophysics, University of California, Berkeley, Berkeley, California, 94720, USA.
Angew Chem Int Ed Engl. 2020 Dec 21;59(52):23668-23677. doi: 10.1002/anie.202008175. Epub 2020 Oct 26.
When nanoparticles enter biological environments, proteins adsorb to form the "protein corona" which alters nanoparticle biodistribution and toxicity. Herein, we measure protein corona formation on DNA-functionalized single-walled carbon nanotubes (ssDNA-SWCNTs), a nanoparticle used widely for sensing and delivery, in blood plasma and cerebrospinal fluid. We characterize corona composition by mass spectrometry, revealing high-abundance corona proteins involved in lipid binding, complement activation, and coagulation. We investigate roles of electrostatic and entropic interactions driving selective corona formation. Lastly, we study real-time protein binding on ssDNA-SWCNTs, obtaining agreement between enriched proteins binding strongly and depleted proteins binding marginally, while highlighting cooperative adsorption mechanisms. Knowledge of protein corona composition, formation mechanisms, and dynamics informs nanoparticle translation from in vitro design to in vivo application.
当纳米粒子进入生物环境时,蛋白质会吸附在其表面形成“蛋白质冠”,从而改变纳米粒子的生物分布和毒性。在本研究中,我们测量了 DNA 功能化单壁碳纳米管(ssDNA-SWCNTs)在血浆和脑脊液中的蛋白质冠形成情况,ssDNA-SWCNTs 是一种广泛用于传感和输送的纳米粒子。我们通过质谱法对冠层组成进行了表征,揭示了与脂质结合、补体激活和凝血相关的高丰度冠层蛋白。我们研究了静电和熵驱动选择性冠形成的作用。最后,我们研究了 ssDNA-SWCNTs 上的实时蛋白质结合情况,发现结合较强的丰富蛋白和结合较弱的耗尽蛋白之间存在一致性,同时突出了协同吸附机制。对蛋白质冠组成、形成机制和动力学的了解可将纳米粒子从体外设计转化为体内应用。