Encapsulation of Hydrophilic and Hydrophobic Peptides into Hollow Mesoporous Silica Nanoparticles for Enhancement of Antitumor Immune Response

Xie Jun; Yang Chaohua; Liu Qianqian; Li Jun; Liang Ruijing; Shen Chen; Zhang Yi; Wang Ke; Liu Liping; Shezad Khurram; Sullivan Martin; Xu Yong; Shen Guanxin; Tao Juan; Zhu Jintao; Zhang Zhiping

摘要

Abstract > Codelivery of combinational antigenic peptides and adjuvant to antigen presenting cells is expected to amplify tumor specific T lymphocytes immune responses while minimizing the possibility of tumor escaping and reducing immune tolerance to single antigenic peptide. However, the varied hydrophobicities of these multivariant derived short antigenic peptides limit their codelivery efficiency in conventional delivery systems. Here, a facile yet effective route is presented to generate monodisperse and stable hollow mesoporous silica nanoparticles (HMSNs) for codelivering of HGP100 <sub>25–33</sub> and TRP2 <sub>180–188</sub> , two melanoma‐derived peptides with varied hydrophobicities. The HMSNs with large pore size can improve the encapsulation efficiency of both HGP100 and TRP2 after ?NH <sub>2</sub> modification on the inner hollow core and ?COOH modification in the porous channels. HGP100 and TRP2 loaded HMSNs (HT@HMSNs) are further enveloped within monophosphoryl lipid A adjuvant entrapped lipid bilayer (HTM@HMLBs), for improved stability/biocompatibility and codelivery efficiency of multiple peptides, adjuvant, and enhanced antitumor immune responses. HTM@HMLBs increase uptake by dendritic cells (DCs) and stimulate DCs maturation efficiently, which further induce the activation of both tumor specific CD8 + and CD4 + T lymphocytes. Moreover, HTM@HMLBs can significantly inhibit tumor growth and lung metastasis in murine melanoma models with good safety profiles. HMSNs enveloped with lipid bilayers (HMLBs) are believed to be a promising platform for codelivery of multiple peptides, adjuvant, and enhancement of antitumor efficacy of conventional vaccinations. </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 XMLNS =“http://www.wiley.com/namespaces/wiley”type =“main”xml：lang =“en”> <title type =“main”>抽象</ title> > codelivery组合抗原肽和助剂对抗原呈递细胞预计会扩增肿瘤特异性T淋巴细胞免疫应答，同时最小化肿瘤逸出并降低单一抗原肽的免疫耐受性。然而，这些多变量衍生的短抗原肽的各种疏水性限制了传统递送系统中的编码效率。这里，提出了一种容易且有效的路线，以产生单分散和稳定的中空介孔二氧化硅纳米颗粒（HMSNS），用于对HGP100 <sub> 25-33 </ sub>和TRP2 <sub> 180-188 </ sub>，两个黑素瘤多重疏水性的肽。具有大孔径大的HMSN可以在内部中空核心上的NH <sub> 2 </ sub>修饰后提高HGP100和TRP2的封装效率和多孔通道中的COOH改性。 HGP100和TRP2加载的HMSNS（HT / HMSNS）进一步包裹在单磷虾脂质中，佐剂夹住脂质双层（HTM @ HMLB），用于改善多种肽，佐剂和增强抗肿瘤免疫应答的稳定性/生物相容性和编码效率。 HTM @ HMLBs通过树突细胞（DCS）增加并有效地刺激DCS成熟，进一步诱导肿瘤特异性CD8 + </ sup>和CD4 + </ sup> t淋巴细胞的活化。此外，HTM @ HMLBs可以显着抑制鼠黑色素瘤模型中的肿瘤生长和肺转移，具有良好的安全性曲线。 HMSNS被封装在脂质双层（HMLBs）包围的HMSNS是一种有前途的平台，用于多种肽，佐剂和常规接种疫苗的抗肿瘤功效的增强。 </ p> </ abstract> </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-28247/'>《Small 》</a> <b style="margin: 0 2px;">|</b><span>2017年第40期</span><b style="margin: 0 2px;">|</b> <span>共1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=Xie Jun&option=202" target="_blank" rel="nofollow">Xie Jun;</a> <a href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=Yang Chaohua&option=202" target="_blank" rel="nofollow">Yang Chaohua;</a> <a href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=Liu Qianqian&option=202" target="_blank" rel="nofollow">Liu Qianqian;</a> <a href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=Li Jun&option=202" target="_blank" rel="nofollow">Li Jun;</a> <a href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=Liang Ruijing&option=202" target="_blank" rel="nofollow">Liang Ruijing;</a> <a href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=Shen Chen&option=202" target="_blank" rel="nofollow">Shen Chen;</a> <a href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=Zhang Yi&option=202" target="_blank" rel="nofollow">Zhang Yi;</a> <a href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=Wang Ke&option=202" target="_blank" rel="nofollow">Wang Ke;</a> <a href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=Liu Liping&option=202" target="_blank" rel="nofollow">Liu Liping;</a> <a href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=Shezad Khurram&option=202" target="_blank" rel="nofollow">Shezad Khurram;</a> <a href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=Sullivan Martin&option=202" target="_blank" rel="nofollow">Sullivan Martin;</a> <a href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=Xu Yong&option=202" target="_blank" rel="nofollow">Xu Yong;</a> <a href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=Shen Guanxin&option=202" target="_blank" rel="nofollow">Shen Guanxin;</a> <a href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=Tao Juan&option=202" target="_blank" rel="nofollow">Tao Juan;</a> <a href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=Zhu Jintao&option=202" target="_blank" rel="nofollow">Zhu Jintao;</a> <a href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=Zhang Zhiping&option=202" target="_blank" rel="nofollow">Zhang Zhiping;</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>Tongji School of Pharmacy and National Engineering Research Center for NanomedicineHuazhong University of Science and Technology (HUST)Wuhan 430030 China;</p> <p>Tongji School of Pharmacy and National Engineering Research Center for NanomedicineHuazhong University of Science and Technology (HUST)Wuhan 430030 China;</p> <p>School of Chemistry and Chemical EngineeringHUSTWuhan 430074 China;</p> <p>Department of DermatologyHUSTWuhan 430022 China;</p> <p>School of Chemistry and Chemical EngineeringHUSTWuhan 430074 China;</p> <p>Department of DermatologyHUSTWuhan 430022 China;</p> <p>Department of DermatologyHUSTWuhan 430022 China;</p> <p>School of Chemistry and Chemical EngineeringHUSTWuhan 430074 China;</p> <p>School of Chemistry and Chemical EngineeringHUSTWuhan 430074 China;</p> <p>School of Chemistry and Chemical EngineeringHUSTWuhan 430074 China;</p> <p>School of Chemistry and Chemical EngineeringHUSTWuhan 430074 China;</p> <p>Department of ImmunologyHUSTWuhan 430022 China;</p> <p>Department of ImmunologyHUSTWuhan 430022 China;</p> <p>Department of DermatologyHUSTWuhan 430022 China;</p> <p>School of Chemistry and Chemical EngineeringHUSTWuhan 430074 China;</p> <p>Tongji School of Pharmacy and National Engineering Research Center for NanomedicineHuazhong University of Science and Technology (HUST)Wuhan 430030 China;</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/6960.html" title="特种结构材料">特种结构材料 ;</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=codelivery&option=203" rel="nofollow">codelivery;</a> <a style="color: #3E7FEB;" href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=hollow mesoporous nanoparticles&option=203" rel="nofollow">hollow mesoporous nanoparticles;</a> <a style="color: #3E7FEB;" href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=immune response&option=203" rel="nofollow">immune response;</a> <a style="color: #3E7FEB;" href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=MPLA&option=203" rel="nofollow">MPLA;</a> <a style="color: #3E7FEB;" href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=peptides&option=203" rel="nofollow">peptides;</a> </p> <div class="translation"> 机译：Codelivery;中空介孔纳米颗粒;免疫应答;MPLA;肽; </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/0704024267052.html">Encapsulation of Hydrophilic and Hydrophobic Peptides into Hollow Mesoporous Silica Nanoparticles for Enhancement of Antitumor Immune Response</a> <b>[J]</b> . <span> <a href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=Xie Jun&option=202" target="_blank" rel="nofollow" class="tuijian_auth tuijian_authcolor">Xie Jun,</a> <a href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=Yang Chaohua&option=202" target="_blank" rel="nofollow" class="tuijian_auth tuijian_authcolor">Yang Chaohua,</a> <a 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