Chemical Engineering Department, Bogazici University, Bebek, Istanbul 34342, Turkey.
Chem Res Toxicol. 2021 Apr 19;34(4):1055-1068. doi: 10.1021/acs.chemrestox.0c00468. Epub 2021 Mar 12.
Polystyrene latex (PSL) nanoparticles (NPs), 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC) liposomes, and hybrid NPs that have different concentrations, sizes, surface charges, and functional groups were used to determine their toxicity to cells. The size, charge, and morphology of the nanoparticles were characterized by dynamic light scattering, electrophoretic light scattering, scanning transmission electron microscopy, and transmission electron microscopy analysis. The cell viabilities were determined by colony forming unit analysis and confocal laser scanning microscopy imaging. Uptake inhibition studies were performed to determine the internalization mechanism of PSL NPs. At 50 mg/L, both positively and negatively charged NPs were slightly toxic. With increasing concentration, however, full toxicities were observed with positively charged PSL NPs, while a marginal increase in toxicity was obtained with negatively charged PSL NPs. For negatively charged and carboxyl-functionalized NPs, an increase in size induced toxicity, whereas for positively charged and amine-functionalized NPs, smaller-sized NPs were more toxic to yeast cells. Negatively charged NPs were internalized by the yeast cells, but they showed toxicity when they entered the cell vacuole. Positively charged NPs, however, accumulated on the cell surface and caused toxicity. When coated with DOPC liposomes, positively charged NPs became significantly less toxic. We attribute this reduction to the larger-diameter and/or more-agglomerated NPs in the extracellular environment, which resulted in lower interactions with the cell. In addition to endocytosis, it is possible that the negatively charged NPs (30-C-n) were internalized by the cells, partly via direct permeation, which is preferred for high drug delivery efficiency. Negatively charged PSL NP exposure to the yeast cells at low-to-moderate concentrations resulted in low toxicities in the long term. Our results indicate that negatively charged PSL NPs provide safer alternatives as cargo carriers in drug delivery applications. Moreover, the variations in NP size, concentration, and exposure time, along with the use of hybrid systems, have significant roles in nanoparticle-based drug delivery applications in terms of their effects on living organisms.
聚苯乙烯乳胶 (PSL) 纳米颗粒 (NPs)、1,2-二油酰基-sn-甘油-3-磷酸胆碱 (DOPC) 脂质体和具有不同浓度、大小、表面电荷和官能团的混合 NPs 被用于确定它们对细胞的毒性。通过动态光散射、电泳光散射、扫描透射电子显微镜和透射电子显微镜分析来表征纳米颗粒的大小、电荷和形态。通过集落形成单位分析和共聚焦激光扫描显微镜成像来确定细胞活力。进行摄取抑制研究以确定 PSL NPs 的内化机制。在 50mg/L 时，带正电荷和负电荷的 NPs 都略有毒性。然而，随着浓度的增加，带正电荷的 PSL NPs 表现出完全毒性，而带负电荷的 PSL NPs 毒性略有增加。对于带负电荷和羧基功能化的 NPs，粒径的增加会引起毒性，而对于带正电荷和胺功能化的 NPs，较小粒径的 NPs 对酵母细胞的毒性更大。带负电荷的 NPs 被酵母细胞内化，但当它们进入细胞液泡时会显示出毒性。然而，带正电荷的 NPs 则在细胞表面聚集并引起毒性。当用 DOPC 脂质体包覆时，带正电荷的 NPs 的毒性显著降低。我们将这种降低归因于细胞外环境中较大直径和/或更聚集的 NPs，这导致与细胞的相互作用降低。除了内吞作用之外，带负电荷的 NPs (30-C-n) 还可能通过部分直接渗透被细胞内化，这对于高药物递送效率是优选的。带负电荷的 PSL NP 在低至中等浓度下暴露于酵母细胞中，在长期内导致低毒性。我们的结果表明，带负电荷的 PSL NPs 作为药物递送应用中的载药载体提供了更安全的替代品。此外，NP 大小、浓度和暴露时间的变化以及混合系统的使用，在基于纳米颗粒的药物递送应用中对生物体的影响方面具有重要作用。
