NMPA Key Laboratory for Technology Research and Evaluation of Drug Products and Key Laboratory of Chemical Biology (Ministry of Education), Department of Pharmaceutics, School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, 44 Cultural West Road, Shandong Province 250012, China.
Shandong University of Traditional Chinese Medicine, Jinan, Shandong Province 250355, China.
J Control Release. 2023 May;357:620-629. doi: 10.1016/j.jconrel.2023.04.013. Epub 2023 Apr 24.
Neutrophil extracellular traps (NETs) are web-like chromatin structures that are coated with granule proteins and trap microorganisms. However, NETs can damage the host tissue, contribute to the development of autoimmunity and lead to other dysfunctional outcomes in noninfectious diseases, including systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), diabetes, atherosclerosis, vasculitis, thrombosis, and cancer. As a potential therapeutic approach, targeted ablation of neutrophil extracellular traps is of utmost importance for the treatment of NET-associated diseases. Here, the specific interaction between CCDC25 and NETs was exploited to produce biomimetic CCDC25-overexpressing cell membrane hybrid liposomes capable of targeting NETs in NET-associated diseases. The hybrid liposomes were constructed by fusing cell membrane nanovesicles derived from genetically engineered cells, which stably express CCDC25, and the resulting cell membrane hybrid liposomes exhibited enhanced affinity for NETs in two different NET-associated disease models. Furthermore, after encapsulation of DNase I in the liposomes, the nanoformulation efficiently eliminated NETs and significantly suppressed the recruitment of neutrophils. Overall, we present a bionic nanocarrier that specifically targets NETs in vivo and successfully inhibits colorectal cancer liver metastases; importantly, this could be a promising therapeutic approach for the treatment of NET-associated diseases.
中性粒细胞胞外诱捕网(NETs)是一种网状染色质结构,其表面覆盖有颗粒蛋白,可捕获微生物。然而,NETs 可损伤宿主组织,促进自身免疫的发展,并导致非传染性疾病的其他功能障碍,包括系统性红斑狼疮(SLE)、类风湿关节炎(RA)、糖尿病、动脉粥样硬化、血管炎、血栓形成和癌症。作为一种潜在的治疗方法,靶向中性粒细胞胞外诱捕网的消融对于治疗与 NET 相关的疾病至关重要。在这里,利用 CCDC25 与 NETs 的特异性相互作用,制备了仿生 CCDC25 过表达细胞膜杂交脂质体,能够靶向与 NET 相关的疾病中的 NETs。该杂交脂质体是通过融合稳定表达 CCDC25 的基因工程细胞衍生的细胞膜纳米囊泡构建而成,所得细胞膜杂交脂质体在两种不同的与 NET 相关的疾病模型中对 NETs 表现出增强的亲和力。此外,将 DNase I 包封在脂质体中后,该纳米制剂可有效消除 NETs,并显著抑制中性粒细胞的募集。总的来说,我们提出了一种仿生纳米载体,可在体内特异性靶向 NETs,并成功抑制结直肠癌肝转移;重要的是,这可能是治疗与 NET 相关的疾病的一种很有前途的治疗方法。