Fahy Kira M, Eiken Madeline K, Baumgartner Karl V, Leung Kaitlyn Q, Anderson Sarah E, Berggren Erik, Bouzos Evangelia, Schmitt Lauren R, Asuri Prashanth, Wheeler Korin E
Department of Chemistry & Biochemistry, Santa Clara University, Santa Clara, California95053, United States.
Department of Bioengineering, Santa Clara University, Santa Clara, California95053, United States.
ACS Omega. 2023 Jan 10;8(3):3310-3318. doi: 10.1021/acsomega.2c06882. eCollection 2023 Jan 24.
Engineered nanomaterials (ENMs) are synthesized with a diversity of surface chemistries that mediate biochemical interactions and physiological response to the particles. In this work, silver engineered nanomaterials (AgENMs) are used to evaluate the role of surface charge in protein interactions and cellular cytotoxicity. The most abundant protein in blood, human serum albumin (HSA), was interacted with 40 nm AgENMs with a range of surface-charged coatings: positively charged branched polyethyleneimine (bPEI), negatively charged citrate (CIT), and circumneutral poly(ethylene glycol) (PEG). HSA adsorption to AgENMs was monitored by UV-vis spectroscopy and dynamic light scattering, while changes to the protein structure were evaluated with circular dichroism spectroscopy. Binding affinity for citrate-coated AgENMs and HSA is largest among the three AgENM coatings; yet, HSA lost the most secondary structure upon interaction with bPEI-coated AgENMs compared to the other two coatings. HSA increased AgENM oxidative dissolution across all particle types, with the greatest dissolution for citrate-coated AgENMs. Results indicate that surface coating is an important consideration in transformation of both the particle and protein upon interaction. To connect results to cellular outcomes, we also performed cytotoxicity experiments with HepG2 cells across all three AgENM types with and without HSA. Results show that bPEI-coated AgENMs cause the greatest loss of cell viability, both with and without inclusion of HSA with the AgENMs. Thus, surface coatings on AgENMs alter both biophysical interactions with proteins and particle cytotoxicity. Within this study set, positively charged bPEI-coated AgENMs cause the greatest disruption to HSA structure and cell viability.
工程纳米材料（ENMs）通过多种表面化学方法合成，这些表面化学方法介导了生物化学相互作用以及对颗粒的生理反应。在这项工作中，银工程纳米材料（AgENMs）被用于评估表面电荷在蛋白质相互作用和细胞毒性中的作用。血液中最丰富的蛋白质，即人血清白蛋白（HSA），与具有一系列表面电荷涂层的40纳米AgENMs相互作用：带正电荷的支化聚乙烯亚胺（bPEI）、带负电荷的柠檬酸盐（CIT）和接近中性的聚乙二醇（PEG）。通过紫外可见光谱和动态光散射监测HSA对AgENMs的吸附，同时用圆二色光谱评估蛋白质结构的变化。在三种AgENM涂层中，柠檬酸盐涂层的AgENMs与HSA的结合亲和力最大；然而，与其他两种涂层相比，HSA在与bPEI涂层的AgENMs相互作用时失去的二级结构最多。HSA在所有颗粒类型中都增加了AgENM的氧化溶解，柠檬酸盐涂层的AgENMs溶解程度最大。结果表明，表面涂层是相互作用时颗粒和蛋白质转变的一个重要考虑因素。为了将结果与细胞结果联系起来，我们还对三种AgENM类型的HepG2细胞进行了有无HSA的细胞毒性实验。结果表明，无论有无HSA，bPEI涂层的AgENMs都会导致最大程度的细胞活力丧失。因此，AgENMs上的表面涂层改变了与蛋白质的生物物理相互作用以及颗粒的细胞毒性。在本研究组中，带正电荷的bPEI涂层的AgENMs对HSA结构和细胞活力造成的破坏最大。
