Stomatological Hospital of Chongqing Medical University, Chongqing Key Laboratory of Oral Diseases and Biomedical Sciences, Chongqing Municipal Key Laboratory of Oral Biomedical Engineering of Higher Education, Chongqing, P. R. China.
Department of Oral Sciences, Sir John Walsh Research Institute, Faculty of Dentistry, University of Otago, Dunedin, New Zealand.
Cell Prolif. 2023 Oct;56(10):e13470. doi: 10.1111/cpr.13470. Epub 2023 Apr 13.
Macrophages' activation plays a central role during the development and progression of inflammation, while the regulation of metabolic reprogramming of macrophages has been recently identified as a novel strategy for anti-inflammatory therapies. Our previous studies have found that tetrahedral framework nucleic acid (tFNA) plays a mild anti-inflammatory effect by inhibiting macrophage activation, but the specific mechanism remains unclear. Here, by metabolomics and RNA sequencing, choline uptake is identified to be significantly repressed by decreased slc44a1 expression in tFNA-treated activated macrophages. Inspired by this result, combined with the excellent delivery capacities of tFNA, siR-slc44a1 is loaded into the tFNA to develop a new tFNA-based small interfering RNA (siRNA) delivery system named 'nano-windmill,' which exhibits a synergetic role by targeting slc44a1, finally blowing up the anti-inflammatory effects of tFNA to inhibit macrophages activation via reducing choline uptake. By confirming its anti-inflammatory effects in chronic (periodontitis) and acute (sepsis) inflammatory disease, the tFNA-based nanomedicine developed for inflammatory diseases may provide broad prospects for tFNA upgrading and various biological applications such as anti-inflammatory.
巨噬细胞的激活在炎症的发生和发展中起着核心作用，而巨噬细胞代谢重编程的调节最近被确定为抗炎治疗的一种新策略。我们之前的研究发现，四面体核酸（tFNA）通过抑制巨噬细胞的激活发挥轻度的抗炎作用，但具体机制尚不清楚。在这里，通过代谢组学和 RNA 测序，发现 tFNA 处理的激活巨噬细胞中 slc44a1 表达降低，导致胆碱摄取明显受到抑制。受此结果启发，结合 tFNA 的优异递药能力，将 siR-slc44a1 载入 tFNA 中开发了一种新型 tFNA 基小干扰 RNA（siRNA）递药系统，命名为“纳米风车”，通过靶向 slc44a1 发挥协同作用，最终通过减少胆碱摄取来增强 tFNA 的抗炎作用，抑制巨噬细胞的激活。通过证实其在慢性（牙周炎）和急性（败血症）炎症性疾病中的抗炎效果，为炎症性疾病开发的基于 tFNA 的纳米药物可能为 tFNA 升级和抗炎等各种生物应用提供广阔的前景。
