Probing the Mechanism of Antibody-Triggered Aggregation of Gold Nanoparticles
Probing the Mechanism of Antibody-Triggered Aggregation of Gold Nanoparticles
复制标题
DOI：
10.1021/acs.langmuir.1c00100
复制
发表时间：
2021-02-23
期刊：
影响因子：
3.9
通讯作者：
Driskell, Jeremy D.
中科院分区：
文献类型：
--
作者：
Okyem, Samuel;Awotunde, Olatunde;Driskell, Jeremy D.
金纳米粒子（AuNPs）独特的物理化学性质为开发新型生物医学技术提供了许多机会。AuNP的表面化学可以被工程化以执行各种功能，包括靶向结合、细胞摄取或通过生物分子（例如蛋白质）的固定化的隐形性质。众所周知，蛋白质可以自发地吸附到AuNP上，以形成稳定且功能性的生物缀合物;然而，蛋白质-AuNP相互作用可能导致形成不太理想的蛋白质-AuNP聚集体。因此，研究蛋白质与金纳米粒子的相互作用并阐明蛋白质触发金纳米粒子聚集的机制是非常必要的。在本文中，我们系统地研究了免疫球蛋白G（IgG）抗体与柠檬酸盐封端的AuNP的相互作用作为溶液pH的函数。我们发现，抗体的添加在pH < 7.5时触发AuNP的聚集，而当抗体在pH >= 7.5时被添加到AuNP时，抗体的单层吸附到AuNP上以形成稳定的生物缀合物。我们的数据确定了抗体和带负电荷的金纳米颗粒之间的静电桥接作为发生聚集的机制，并排除了蛋白质解折叠和表面电荷耗尽作为潜在原因。此外，我们发现，静电桥接的金纳米粒子是可逆的，在最初的几个小时内的相互作用，但蛋白质-金纳米粒子的相互作用加强超过24小时，之后的蛋白质-金纳米粒子的聚集体是不可逆的形成。根据这些数据，我们开发了一种直接的方法来丙烯酸酯抗体上的碱性残基，以防止蛋白质诱导的AuNP在宽pH范围内聚集。本研究的结果为抗体-纳米颗粒相互作用提供了额外的见解，并提供了一种控制相互作用的途径，具有增强缀合物功能的潜力。
The unique physicochemical properties of gold nanoparticles (AuNPs) provide many opportunities to develop novel biomedical technologies. The surface chemistry of AuNPs can be engineered to perform a variety of functions, including targeted binding, cellular uptake, or stealthlike properties through the immobilization of biomolecules, such as proteins. It is well established that proteins can spontaneously adsorb onto AuNPs, to form a stable and functional bioconjugate; however, the protein-AuNP interaction may result in the formation of less desirable protein-AuNP aggregates. Therefore, it is imperative to investigate the protein-AuNP interaction and elucidate the mechanism by which protein triggers AuNP aggregation. Herein, we systematically investigated the interaction of immunoglobulin G (IgG) antibody with citrate-capped AuNPs as a function of solution pH. We found that the addition of antibody triggers the aggregation of AuNPs for pH < 7.5, whereas a monolayer of antibody adsorbs onto the AuNP to form a stable bioconjugate when the antibody is added to AuNPs at pH >= 7.5. Our data identifies electrostatic bridging between the antibody and the negatively charged AuNPs as the mechanism by which aggregation occurs and rules out protein unfolding and surface charge depletion as potential causes. Furthermore, we found that the electrostatic bridging of AuNPs is reversible within the first few hours of interaction, but the protein-AuNP interactions strengthen over 24 h, after which the protein-AuNP aggregate is irreversibly formed. From this data, we developed a straightforward approach to acrylate the basic residues on the antibody to prevent protein-induced aggregation of AuNP over a wide pH range. The results of this study provide additional insight into antibody-nanoparticle interactions and provide a pathway to control the interaction with the potential to enhance the conjugate function.