Center for Neuroscience and Cell Biology, University of Coimbra, 3000-548 Coimbra, Portugal.
Department of Pharmaceutical Technology, Faculty of Pharmacy, University of Coimbra, 3000-548 Coimbra, Portugal.
Chem Res Toxicol. 2020 Apr 20;33(4):915-932. doi: 10.1021/acs.chemrestox.9b00467. Epub 2020 Mar 19.
Glucan (from ) is a polymer composed of β-1,3-linked glucose residues, and it has been addressed in different medical fields, namely in nanotechnology, as a vaccine or a drug delivery system. However, due to their small size, nanomaterials may present new risks and uncertainties. Thus, this work aims to describe the production of glucan nanoparticles (NPs) with two different sizes, and to evaluate the influence of the NPs size on immunotoxicity. Results showed that, immediately after production, glucan NPs presented average sizes of 129.7 ± 2.5 and 355.4 ± 41.0 nm. Glucan NPs of 130 nm presented greater ability to decrease human peripheral blood mononuclear cells and macrophage viability and to induce reactive oxygen species production than glucan NPs of 355 nm. Both NP sizes caused hemolysis and induced a higher metabolic activity in lymphocytes, although the concentration required to observe such effect was lower for the 130 nm glucan NPs. Regarding pro-inflammatory cytokines, only the larger glucan NPs (355 nm) were able to induce the secretion of IL-6 and TNF-α, probably due to their recognition by dectin-1. This higher immunomodulatory effect of the larger NPs was also observed in its ability to stimulate the production of nitric oxide (NO) and IL-1β. On the contrary, a small amount of Glu 130 NPs inhibited NO production. In conclusion, on the safe-by-design of glucan NPs, the size of the particles should be an important critical quality attribute to guarantee the safety and effectiveness of the nanomedicine.
葡聚糖（来自 ）是一种由β-1,3 键合的葡萄糖残基组成的聚合物，已在不同的医学领域得到应用，例如纳米技术，作为疫苗或药物递送系统。然而，由于其尺寸较小，纳米材料可能会带来新的风险和不确定性。因此，本工作旨在描述两种不同尺寸的葡聚糖纳米颗粒（NPs）的生产，并评估 NPs 尺寸对免疫毒性的影响。结果表明，葡聚糖 NPs 在生产后立即呈现出平均尺寸为 129.7±2.5nm 和 355.4±41.0nm。与 355nm 的葡聚糖 NPs 相比，粒径为 130nm 的葡聚糖 NPs 具有更大的降低人外周血单核细胞和巨噬细胞活力以及诱导活性氧产生的能力。两种 NP 尺寸均导致溶血并诱导淋巴细胞代谢活性增加，尽管观察到这种效应所需的浓度较低。关于促炎细胞因子，只有较大的葡聚糖 NPs（355nm）能够诱导 IL-6 和 TNF-α 的分泌，这可能是由于其被 dectin-1 识别。较大 NPs 的这种更高的免疫调节作用也表现在其刺激一氧化氮（NO）和 IL-1β 产生的能力上。相反，少量的 Glu 130 NPs 抑制了 NO 的产生。总之，在葡聚糖 NPs 的安全设计方面，颗粒的大小应该是保证纳米医学安全性和有效性的一个重要关键质量属性。
