Department of Chemical Engineering, University of Rochester, Gavett Hall 206, Rochester, NY 14627, USA and Department of Chemical and Biomolecular Engineering, University of Illinois at Urbana-Champaign, 600 S. Matthews Avenue, 114 Roger Adams Laboratory, MC-712, Urbana, IL 61801, USA.
Department of Pathology and Laboratory Medicine, University of Rochester, 601 Elmwood Ave, Rochester, NY 14642, USA.
Nanoscale. 2017 Apr 6;9(14):4739-4750. doi: 10.1039/c6nr09102d.
The understanding of nanoparticle (NP) cytotoxicity is challenging because of incomplete information about physicochemical changes particles undergo once they come into contact with biological fluids. It is therefore essential to characterize changes in NP properties to better understand their biological fate and effects in mammalian cells. In this paper, we present a study on the effect of particle surface oxidation and dissolution rates of Cu NPs. Particle dissolution, cell-associated Cu doses, and oxidative stress responses in A549 luciferase reporter cells were examined for Cu NPs modified with mercaptocarboxylic acids with different carbon chain lengths and a thiotic acid appended-PEG ligand (TA). We found that these Cu NPs released ionic species together with small particles upon oxidation and that surface chemistry influenced the morphology and dissolution rate. The dissolution rate was also shown to impact both the cellular Cu dosimetry and associated oxidative stress responses. The convergent results from dissolution and dosimetry measurements demonstrate that both intracellular and extracellular (i.e., NP uptake-independent) release of ionic species from Cu NPs greatly affect the cytotoxicity.
纳米颗粒（NP）细胞毒性的理解具有挑战性，因为一旦它们与生物流体接触，关于颗粒经历的物理化学变化的信息并不完整。因此，描述 NP 特性的变化对于更好地了解它们在哺乳动物细胞中的生物学命运和影响至关重要。在本文中，我们研究了颗粒表面氧化和 Cu NPs 溶解速率对其的影响。对于用具有不同碳链长度的巯基羧酸和连接有硫代酸的聚乙二醇配体（TA）修饰的 Cu NPs，我们检测了其在 A549 荧光素报告细胞中的粒子溶解、细胞内 Cu 剂量和氧化应激反应。我们发现这些 Cu NPs 在氧化时会释放出离子物种和小颗粒，而表面化学会影响其形态和溶解速率。溶解速率也显示出对细胞内 Cu 计量学和相关氧化应激反应的影响。溶解和计量学测量的收敛结果表明，Cu NPs 从细胞内和细胞外（即与 NP 摄取无关）释放的离子物种都会极大地影响细胞毒性。
