The nano-windmill exerts superior anti-inflammatory effects via reducing choline uptake to inhibit macrophage activation

作者全名："Liu, Nanxin; Zhong, Yuke; Pang, Xiaoxiao; Li, Mingzheng; Cannon, Richard D.; Mei, Li; Cai, Xiaoxiao; Ji, Ping"

作者地址："[Liu, Nanxin; Zhong, Yuke; Pang, Xiaoxiao; Li, Mingzheng; Mei, Li; Ji, Ping] Chongqing Med Univ, Chongqing Key Lab Oral Dis & Biomed Sci, Chongqing Municipal Key Lab Oral Biomed Engn Highe, Stomatol Hosp, Chongqing, Peoples R China; [Cannon, Richard D.; Mei, Li] Univ Otago, Sir John Walsh Res Inst, Fac Dent, Dept Oral Sci, Dunedin, New Zealand; [Cai, Xiaoxiao] Sichuan Univ, Natl Clin Res Ctr Oral Dis, State Key Lab Oral Dis, West China Hosp Stomatol, Chengdu, Peoples R China; [Ji, Ping] Chongqing Med Univ, Chongqing Key Lab Oral Dis & Biomed Sci, Chongqing Municipal Key Lab Oral Biomed Engn Highe, Stomatol Hosp, Chongqing 401120, Peoples R China; [Cai, Xiaoxiao] Sichuan Univ, Natl Clin Res Ctr Oral Dis, State Key Lab Oral Dis, State Key Lab Oral Dis, Chengdu 610041, Peoples R China"

通信作者："Ji, P (通讯作者)，Chongqing Med Univ, Chongqing Key Lab Oral Dis & Biomed Sci, Chongqing Municipal Key Lab Oral Biomed Engn Highe, Stomatol Hosp, Chongqing 401120, Peoples R China.; Cai, XX (通讯作者)，Sichuan Univ, Natl Clin Res Ctr Oral Dis, State Key Lab Oral Dis, State Key Lab Oral Dis, Chengdu 610041, Peoples R China."

来源：CELL PROLIFERATION

ESI学科分类：MOLECULAR BIOLOGY & GENETICS

WOS号：WOS:000970430000001

JCR分区：Q2

影响因子：5.9

年份：2023

卷号：　

期号：　

开始页：　

结束页：　

文献类型：Article; Early Access

关键词：　

摘要："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."

基金机构："National Natural Science Foundation of China [82001058, 82071115, 82220108019]; Natural Science Foundation of Chongqing [CSTB2022NSCQ-MSX0791]; Natural Science Foundation of Sichuan Province [2021YFQ0064]"

基金资助正文："National Natural Science Foundation of China, Grant/Award Numbers: 82001058, 82071115, 82220108019; Natural Science Foundation of Chongqing, Grant/Award Number: CSTB2022NSCQ-MSX0791; Natural Science Foundation of Sichuan Province, Grant/Award Number: 2021YFQ0064"