An elevated reactive oxygen species (ROS) level leads to cellular oxidative stress, which has long been associated with diseases, such as cancer. Thus, the understanding and appropriate manipulation of cellular oxidative stress are needed for disease treatment. It has been reported that nanoparticles induce oxidative stress in human cells through different pathways. However, how the physicochemical properties of nanoparticles perturb cellular oxidative stress remains unclear. In this paper, we explored the effects of the positive/negative charge density and hydrophobicity of gold nanoparticles (GNPs) on the induction of oxidative stress and related mechanisms. In multiple human cell lines, we found that only the positive charge density and hydrophobicity of nanoparticles were correlated with the induction of cellular oxidative stress. Hydrophobic nanoparticles generated oxidative stress mainly through NADPH oxidase activation while positively charged nanoparticles generated it through perturbations of the mitochondria and modulation of intracellular Ca²⁺ concentration. Furthermore, nanoparticle-induced oxidative stress sensitized paclitaxel-induced cancer cell killing by 200%. These findings provided unequivocal structural parameters for the design of future nanomedicine and biocompatible nanocarriers.

中文翻译：

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具有不同电荷密度和疏水性的金纳米颗粒诱导氧化应激并使癌细胞对紫杉醇敏感†

升高的活性氧（ROS）水平会导致细胞氧化应激，长期以来，这种氧化应激与疾病（例如癌症）有关。因此，对于疾病的治疗需要细胞氧化应激的理解和适当的操纵。据报道，纳米颗粒通过不同的途径诱导人细胞中的氧化应激。然而，纳米粒子的理化特性如何扰动细胞的氧化应激仍然不清楚。在本文中，我们探讨了金纳米颗粒（GNP）的正/负电荷密度和疏水性对氧化应激的诱导作用及其相关机理。在多个人类细胞系中，我们发现只有正电荷密度和纳米颗粒的疏水性与细胞氧化应激的诱导相关。²⁺浓度。此外，纳米颗粒诱导的氧化应激使紫杉醇诱导的癌细胞杀伤率提高了200％。这些发现为未来的纳米药物和生物相容性纳米载体的设计提供了明确的结构参数。