Screening of the binding affinity of serum proteins to lipid nanoparticles in a cell free environment.
Screening of the binding affinity of serum proteins to lipid nanoparticles in a cell free environment.
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在无细胞环境中筛选血清蛋白与脂质纳米粒子的结合亲和力。
DOI：
10.1016/j.jcis.2021.11.117
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发表时间：
2021
影响因子：
9.9
通讯作者：
M. Cárdenas
中科院分区：
文献类型：
--
作者：
F. Sebastiani;Marianna Yanez Arteta;L. Lindfors;M. Cárdenas
脂质纳米颗粒（LNPs）是一种很有前途的药物和基因载体。静脉给药后，LNPs的细胞摄取程度取决于其配方。目前，体外研究是评估纳米载体使用后的命运的金标准，但它们既耗时又昂贵。在这项工作中，我们提出了一种时间和成本效益高的方法来筛选广泛的LNP配方，并选择最有希望进行体外和体内研究的候选药物。研究人员探索了两种不同的方法来研究LNPs与血清蛋白之间的结合亲和力，分别使用蛋白质特异性抗体或PEG特异性抗体进行传感器功能化。第一种方法允许在脂质颗粒（重组和天然高密度脂蛋白（rHDL和HDL）以及低密度脂蛋白LDL）的蛋白质冠中识别特定蛋白质的存在；而第二种方法为固定聚乙二醇颗粒提供了一个通用的平台，以便跟踪与血清蛋白的相互作用，从而预测LNP蛋白冠的组成。传感是用耗散石英晶体微天平（QCM-D）完成的，但该方法可扩展到其他表面传感技术，如表面等离子体共振（SPR）或椭偏仪。
Lipid nanoparticles (LNPs) are promising drug and gene carriers. Upon intravenous administration, LNPs’ experience different degree of cellular uptake depending on their formulation. Currently,in vitroandin vivostudies are the gold standard for assessing the fate of nano carriers once administered, but they are time consuming and expensive. In this work, we propose a time and cost-effective method to screen a wide range of LNP formulations and select the most promising candidates forin vitroandin vivostudies. Two different approaches were explored to investigate the binding affinity between LNPs and serum proteins using sensor functionalisation with either protein specific antibody or PEG specific antibody. The first approach allowed to identify the presence of a specific protein in the protein corona of lipid particles (reconstituted and native high-density lipoproteins (rHDL and HDL), and low-density lipoproteins LDL); while the second one provided a versatile platform for the immobilisation of pegylated-particles in order to follow the interaction with serum proteins and hence predict the composition of LNP protein corona. Sensing was done using Quartz Crystal Microbalance with Dissipation (QCM-D) but the approach is extendable to other surface sensing techniques such as Surface Plasmon Resonance (SPR) or ellipsometry.
影响因子：
17.1
作者：
Pilkington EH;Gustafsson OJR;Xing Y;Hernandez-Fernaud J;Zampronio C;Kakinen A;Faridi A;Ding F;Wilson P;Ke PC;Davis TP
通讯作者：
Davis TP