Macrophage‐Targeted Isoniazid–Selenium Nanoparticles Promote Antimicrobial Immunity and Synergize Bactericidal Destruction of Tuberculosis Bacilli

Pi Jiang; Shen Ling; Yang Enzhuo; Shen Hongbo; Huang Dan; Wang Richard; Hu Chunmiao; Jin Hua; Cai Huaihong; Cai Jiye; Zeng Gucheng; Chen Zheng W.

摘要

Abstract >Pathogenesis hallmarks for tuberculosis (TB) are the Mycobacterium tuberculosis (Mtb) escape from phagolysosomal destruction and limited drug delivery into infected cells. Several nanomaterials can be entrapped in lysosomes, but the development of functional nanomaterials to promote phagolysosomal Mtb clearance remains a big challenge. Here, we report on the bactericidal effects of selenium nanoparticles (Se NPs) against Mtb and further introduce a novel nanomaterial‐assisted anti‐TB strategy manipulating Ison@Man‐Se NPs for synergistic drug‐induced and phagolysosomal destruction of Mtb. Ison@Man‐Se NPs preferentially entered macrophages and accumulated in lysosomes releasing Isoniazid. Surprisingly, Ison@Man‐Se/Man‐Se NPs further promoted the fusion of Mtb into lysosomes for synergistic lysosomal and Isoniazid destruction of Mtb. Concurrently, Ison@Man‐Se/Man‐Se NPs also induced autophagy sequestration of Mtb, evolving into lysosome‐associated autophagosomal Mtb degradation linked to ROS‐mitochondrial and PI3K/Akt/mTOR signaling pathways. This novel nanomaterial‐assisted anti‐TB strategy manipulating antimicrobial immunity and Mtb clearance may potentially serve in more effective therapeutics against TB and drug‐resistant TB. </abstract> </span> <span class="z_kbtn z_kbtnclass hoverxs" style="display: none;">展开▼</span> </div> <div class="translation abstracttxt"> <span class="zhankaihshouqi fivelineshidden" id="abstract"> <span>机译：</span><Abstract Type =“Main”XML：Lang =“en”> <标题类型=“main”>抽象</ title> >结核病（TB）的发病机制标志是结核分枝杆菌（MTB）逃离吞噬骨膜破坏和有限的药物输送到感染细胞。几种纳米材料可以捕获溶酶体，但功能纳米材料的发育促进吞噬骨髓MTB间隙仍然是一个很大的挑战。在这里，我们报告硒纳米粒子（SE NPS）对MTB的杀菌作用，进一步引入一种新的纳米材料辅助抗结核病策略，操纵ISON @ MAN-SE NPS的SONON @ MAN-SE NPS，用于MTB的协同药物诱导和吞噬骨髓性破坏。 ISON @ MAN-SE NPS优先进入巨噬细胞并积累在裂解中释放的异烟肼。令人惊讶的是，ISON @ MAN-SE / MAN-SE NPS进一步促进了MTB的融合为溶酶体，用于协同溶酶体和异烟体破坏MTB。同时，ISON @ MAN-SE / MAN-SE NPS还诱导了MTB的自噬封存，而发展成与ROS-MitoCOCOLIAL和PI3K / AKT / MTOR信号传导途径有关的溶酶体相关的自噬体MTB降解。这种新型纳米材料辅助抗TB策略操纵抗菌免疫和MTB间隙可能在更有效的治疗方法中用于针对TB和耐药性TB的更有效。</ p> </摘要> </span> <span class="z_kbtn z_kbtnclass hoverxs" style="display: none;">展开▼</span> </div> </div> <div class="record"> <h2 class="all_title" id="enpatent33" >著录项</h2> <ul> <li> <span class="lefttit">来源</span> <div style="width: 86%;vertical-align: text-top;display: inline-block;"> <a href='/journal-foreign-19011/'>《Angewandte Chemie》</a> <b style="margin: 0 2px;">|</b><span>2020年第8期</span><b style="margin: 0 2px;">|</b><span>共9页</span> </div> </li> <li> <div class="author"> <span class="lefttit">作者</span> <p id="fAuthorthree" class="threelineshidden zhankaihshouqi"> <a href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=Pi Jiang&option=202" target="_blank" rel="nofollow">Pi Jiang;</a> <a href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=Shen Ling&option=202" target="_blank" rel="nofollow">Shen Ling;</a> <a href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=Yang Enzhuo&option=202" target="_blank" rel="nofollow">Yang Enzhuo;</a> <a href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=Shen Hongbo&option=202" target="_blank" rel="nofollow">Shen Hongbo;</a> <a href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=Huang Dan&option=202" target="_blank" rel="nofollow">Huang Dan;</a> <a href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=Wang Richard&option=202" target="_blank" rel="nofollow">Wang Richard;</a> <a href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=Hu Chunmiao&option=202" target="_blank" rel="nofollow">Hu Chunmiao;</a> <a href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=Jin Hua&option=202" target="_blank" rel="nofollow">Jin Hua;</a> <a href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=Cai Huaihong&option=202" target="_blank" rel="nofollow">Cai Huaihong;</a> <a href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=Cai Jiye&option=202" target="_blank" rel="nofollow">Cai Jiye;</a> <a href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=Zeng Gucheng&option=202" target="_blank" rel="nofollow">Zeng Gucheng;</a> <a href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=Chen Zheng W.&option=202" target="_blank" rel="nofollow">Chen Zheng W.;</a> </p> <span class="z_kbtnclass z_kbtnclassall hoverxs" id="zkzz" style="display: none;">展开▼</span> </div> </li> <li> <div style="display: flex;"> <span class="lefttit">作者单位</span> <div style="position: relative;margin-left: 3px;max-width: 639px;"> <div class="threelineshidden zhankaihshouqi" id="fOrgthree"> <p>Department of Microbiology and ImmunologyUniversity of Illinois College of MedicineChicago IL 60612 USA;</p> <p>Department of Microbiology and ImmunologyUniversity of Illinois College of MedicineChicago IL 60612 USA;</p> <p>Department of Microbiology and ImmunologyUniversity of Illinois College of MedicineChicago IL 60612 USA;</p> <p>Clinic and Research Center of Tuberculosis Shanghai Key Lab of TuberculosisTongji University School of MedicineShanghai 200433 China;</p> <p>Department of Microbiology and ImmunologyUniversity of Illinois College of MedicineChicago IL 60612 USA;</p> <p>Department of Microbiology and ImmunologyUniversity of Illinois College of MedicineChicago IL 60612 USA;</p> <p>Department of Microbiology and ImmunologyUniversity of Illinois College of MedicineChicago IL 60612 USA;</p> <p>Department of Microbiology and ImmunologyUniversity of Illinois College of MedicineChicago IL 60612 USA;</p> <p>Department of ChemistryJinan UniversityGuangzhou Guangdong 510632 China;</p> <p>Department of ChemistryJinan UniversityGuangzhou Guangdong 510632 China;</p> <p>Department of MicrobiologySun Yat-sen UniversityGuangzhou Guangdong 510080 China;</p> <p>Department of Microbiology and ImmunologyUniversity of Illinois College of MedicineChicago IL 60612 USA;</p> </div> <span class="z_kbtnclass z_kbtnclassall hoverxs" id="zhdw" style="display: none;">展开▼</span> </div> </div> </li> <li > <span class="lefttit">收录信息</span> <span style="width: 86%;vertical-align: text-top;display: inline-block;"></span> </li> <li> <span class="lefttit">原文格式</span> <span>PDF</span> </li> <li> <span class="lefttit">正文语种</span> <span>eng</span> </li> <li> <span class="lefttit">中图分类</span> <span><a href="https://www.zhangqiaokeyan.com/clc/1188.html" title="应用化学">应用化学;</a></span> </li> <li class="antistop"> <span class="lefttit">关键词</span> <p style="width: 86%;vertical-align: text-top;"> <a style="color: #3E7FEB;" href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=antimicrobial immunity&option=203" rel="nofollow">antimicrobial immunity;</a> <a style="color: #3E7FEB;" href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=drug delivery&option=203" rel="nofollow">drug delivery;</a> <a style="color: #3E7FEB;" href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=phagolysosomal destruction&option=203" rel="nofollow">phagolysosomal destruction;</a> <a style="color: #3E7FEB;" href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=selenium nanoparticles&option=203" rel="nofollow">selenium nanoparticles;</a> <a style="color: #3E7FEB;" href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=tuberculosis&option=203" rel="nofollow">tuberculosis;</a> </p> <div class="translation"> 机译：抗菌免疫;药物递送;吞噬骨膜破坏;硒纳米粒子;结核病; </div> </li> </ul> </div> </div> <div class="literature cardcommon"> <div class="similarity "> <h3 class="all_title" id="enpatent66">相似文献</h3> <div class="similaritytab clearfix"> <ul> <li class="active" >外文文献</li> <li >中文文献</li> <li >专利</li> </ul> </div> <div class="similarity_details"> <ul > <li> <div> <b>1. </b><a class="enjiyixqcontent" href="/journal-foreign-detail/0704028162259.html">Macrophage‐Targeted Isoniazid–Selenium Nanoparticles Promote Antimicrobial Immunity and Synergize Bactericidal Destruction of Tuberculosis Bacilli</a> <b>[J]</b> . <span> <a href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=Pi Jiang&option=202" target="_blank" rel="nofollow" class="tuijian_auth tuijian_authcolor">Pi Jiang,</a> <a 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