Intratracheal administration of programmable DNA nanostructures combats acute lung injury by targeting microRNA-155

作者全名："Huang, Chaowang; Liu, Qian; Xu, Jing; Chen, Chunfa; You, Qianyi; Wang, Dan; Qian, Hang; Hu, Mingdong"

作者地址："[Huang, Chaowang; Xu, Jing; You, Qianyi; Wang, Dan; Hu, Mingdong] Third Mil Med Univ, Xinqiao Hosp, Dept Geriatr & Special Serv Med, Chongqing 400037, Peoples R China; [Huang, Chaowang; Liu, Qian; Chen, Chunfa; You, Qianyi; Qian, Hang] Third Mil Med Univ, Xinqiao Hosp, Inst Resp Dis, Chongqing 400037, Peoples R China; [Liu, Qian] Chongqing Med Univ, Lab Pharm & Chem, Chongqing 400016, Peoples R China; [Liu, Qian] Chongqing Med Univ, Lab Tissue & Cell Biol, Lab Teaching & Management Ctr, Chongqing 400016, Peoples R China; [Qian, Hang] Chongqing Key Lab Precis Med & Prevent Major Resp, Chongqing 400037, Peoples R China; [Hu, Mingdong] Third Mil Med Univ, Xinqiao Hosp, Dept Hlth Management, Chongqing 400037, Peoples R China"

通信作者："Hu, MD (通讯作者)，Third Mil Med Univ, Xinqiao Hosp, Dept Geriatr & Special Serv Med, Chongqing 400037, Peoples R China.; Qian, H (通讯作者)，Third Mil Med Univ, Xinqiao Hosp, Inst Resp Dis, Chongqing 400037, Peoples R China.; Qian, H (通讯作者)，Chongqing Key Lab Precis Med & Prevent Major Resp, Chongqing 400037, Peoples R China."

来源：INTERNATIONAL JOURNAL OF PHARMACEUTICS

ESI学科分类：PHARMACOLOGY & TOXICOLOGY

WOS号：WOS:001153334600001

JCR分区：Q1

影响因子：5.8

年份：2024

卷号：651

期号：　

开始页：　

结束页：　

文献类型：Article; Early Access

关键词：Acute lung injury; DNA nanostructure; Intratracheal administration; MicroRNA-155; Macrophage

摘要："Acute lung injury (ALI) is an acute inflammatory process that can result in life-threatening consequences. Programmable DNA nanostructures have emerged as excellent nanoplatforms for microRNA-based therapeutics, offering potential nanomedicines for ALI treatment. Nonetheless, the traditional systematic administration of nanomedicines is constrained by low delivery efficiency, poor pharmacokinetics, and nonspecific side effects. Here, we identify macrophage microRNA-155 as a novel therapeutic target using the magnetic bead sorting technique. We further construct a DNA nanotubular nucleic acid drug antagonizing microRNA-155 (NT-155) for ALI treatment through intratracheal administration. Flow cytometry results demonstrate that NT-155, when inhaled, is taken up much more effectively by macrophages and dendritic cells in the bronchoalveolar lavage fluid of ALI mice. Furthermore, NT-155 effectively silences the overexpressed microRNA-155 in macrophages and exerts excellent inflammation inhibition effects in vitro and ALI mouse models. Mechanistically, NT-155 suppresses microRNA-155 expression and activates its target gene SOCS1, inhibiting the p-P65 signaling pathway and suppressing proinflammatory cytokine secretion. The current study suggests that deliberately designed nucleic acid drugs are promising nanomedicines for ALI treatment and the local administration may open up new practical applications of DNA in the future."

基金机构："National Key R&D Program of China [2020YFC2008900, 2020YFC2008903]; National Natural Science Foundation of China [81873421]; Natural Science Foundation of Chongqing [cstc2021jcyj-msxmX1179]; Young PhD Incubation Program of Xinqiao Hospital, Army Military Medical [2022YQB024]"

基金资助正文："This work was supported by the National Key R & D Program of China (2020YFC2008900, 2020YFC2008903), the National Natural Science Foundation of China (81873421), the Natural Science Foundation of Chongqing (No. cstc2021jcyj-msxmX1179), and the Young PhD Incubation Program of Xinqiao Hospital, Army Military Medical (2022YQB024)."