Ultrasound Department, West China Hospital of Sichuan University, Chengdu, People's Republic of China.
Laboratory of Ultrasound Imaging, West China Hospital of Sichuan University, Chengdu, People's Republic of China.
Int J Nanomedicine. 2022 Dec 5;17:5933-5946. doi: 10.2147/IJN.S364381. eCollection 2022.
To prepare nanoscale ultrasound contrast agents (Nano-UCAs) and examine the role of their surface charge in complement activation and phagocytosis.
We analyzed serum proteins present in the corona formed on Nano-UCAs and evaluated two important protein markers of complement activation (C3 and SC5b-9). The effect of surface charge on phagocytosis was further assessed using THP-1 macrophages.
When Nano-UCAs were incubated with human serum, they were opsonized by various blood proteins, especially C3. Highly charged Nano-UCAs, whether positive or negative, were favorably opsonized by complement proteins and phagocytized by macrophages.
Charged Nano-UCAs show a higher tendency to activated complement system, and are efficiently engulfed by macrophages. The present results provide meaningful insights into the role of the surface charge of nanoparticles in the activation of the innate immune system, which is important not only for the design of targeted Nano-UCAs, but also for the effectiveness and safety of other theranostic agents.
制备纳米级超声对比剂(Nano-UCAs),并研究其表面电荷在补体激活和吞噬作用中的作用。
我们分析了在 Nano-UCAs 形成的冠状物中存在的血清蛋白,并评估了补体激活的两个重要蛋白标志物(C3 和 SC5b-9)。利用 THP-1 巨噬细胞进一步评估了表面电荷对吞噬作用的影响。
当 Nano-UCAs 与人血清孵育时,它们被各种血液蛋白,特别是 C3 调理。带正电荷或负电荷的高电荷 Nano-UCAs 都被补体蛋白有利地调理,并被巨噬细胞吞噬。
带电荷的 Nano-UCAs 显示出更高的激活补体系统的趋势,并被巨噬细胞有效吞噬。这些结果为纳米粒子表面电荷在先天免疫系统激活中的作用提供了有意义的见解,这不仅对靶向 Nano-UCAs 的设计很重要,而且对其他治疗药物的有效性和安全性也很重要。