Integrated Multifunctional Micelles Co‐Self‐Assembled from Polypeptides Conjugated with Natural Ferulic Acid and Lipoic Acid for Doxorubicin Delivery

Chen Tao; Qiu Min; Zhang Jian; Sun Huanli; Deng Chao; Zhong Zhiyuan

摘要

Abstract > The development of safe, easily accessible, and multifunctional nanocarriers is a big topic in nanomedicine research. Here, integrated multifunctional micelles (IMM) were developed by co‐self‐assembly of poly(ethylene glycol)‐ b ‐poly( <sc>l</sc> ‐lysine) derivatives with natural ferulic acid (FA) or lipoic acid (LA). FA confers IMM with intrinsic antitumor activity, improved loading of doxorubicin (DOX) through π–π stacking, and reduced DOX cardiotoxicity. LA provides IMM with reversible crosslinking property, which leads to a high colloidal stability with inhibited drug leakage and triggered intracellular DOX release. Notably, our results showed that cRGD‐decorated IMM (cRGD‐IMM) had a small size (≈56?nm) and superior loading of DOX (27.1?wt.?%). Blank cRGD‐IMM, though nontoxic to normal cells, exhibited obvious antiproliferative activity against cancer cells including B16F10 and HCT‐116 cells at 150?μg?FA?equiv.?mL ?1 . DOX‐loaded cRGD‐IMM displayed enhanced growth inhibition of α <sub>v</sub> β <sub>3</sub> ‐positive B16F10 and HCT‐116 cells, a long elimination half‐life of 3.85?h, and a high maximum‐tolerated dose of over 100?mg?DOX?equiv.?kg ?1 . Histological analysis revealed that DOX‐loaded cRGD‐IMM at 100?mg?DOX?equiv.?kg ?1 caused negligible cardiotoxicity, which is a major issue for the clinical use of DOX. These integrated multifunctional micelles with excellent safety and accessibility have emerged as a new platform for targeted cancer chemotherapy. </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> >安全，易于访问和多功能纳米载波的开发是纳米医生研究中的一个大主题。这里，通过聚（乙二醇） - B -poly（<sc> l </ sc> -Lysine）衍生物具有天然脱硫酸的共同自组装，开发了集成的多官能胶束（Imm）。（Fa）或硫辛酸（La）。 FA赋予内在抗肿瘤活性的IMM，通过π-π堆叠改善了多柔比星（DOX）的载荷，降低了DOX心脏毒性。 La提供可逆交联性能，导致高胶体稳定性，抑制药物泄漏并引发细胞内DOX释放。值得注意的是，我们的结果表明，CRGD装饰的IMM（CRGD-IMM）的尺寸小（≈56Ω·纳米）和多种载荷的优异载荷（27.1〜wt。？％）。空白CRGD-IMM虽然没有毒性对正常细胞，对包括B16F10和HCT-116细胞的癌细胞表现出明显的抗增殖活性，在150Ω·μg≤ab≤af中的癌细胞。 DOX加载的CRGD-IMM显示增强的生长抑制α</ i> <sub> v </ sub> β</ i> <sub> 3 </ sub> -positive b16f10和hct-116细胞，长度消除半衰期为3.85Ωh，以及超过100Ω·mg的高最大耐受剂量？DOX？当量。kg ？1 </ sup>。组织学分析显示，DOX加载的CRGD-IMM在100？MG？DOX？CANIF。？KG <SUP>？1 </ sup>引起忽略不计的心毒性，这是DOX临床使用的主要问题。这些集成的多功能胶束具有出色的安全性和可访问性，作为针对癌症化学疗法的新平台。 </ 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-16300/'>《Chemphyschem: A European journal of chemical physics and physical chemistry》</a> <b style="margin: 0 2px;">|</b><span>2018年第16期</span><b style="margin: 0 2px;">|</b><span>共8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=Chen Tao&option=202" target="_blank" rel="nofollow">Chen Tao;</a> <a href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=Qiu Min&option=202" target="_blank" rel="nofollow">Qiu Min;</a> <a href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=Zhang Jian&option=202" target="_blank" rel="nofollow">Zhang Jian;</a> <a href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=Sun Huanli&option=202" target="_blank" rel="nofollow">Sun Huanli;</a> <a href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=Deng Chao&option=202" target="_blank" rel="nofollow">Deng Chao;</a> <a href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=Zhong Zhiyuan&option=202" target="_blank" rel="nofollow">Zhong Zhiyuan;</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>Biomedical Polymers Laboratory and Jiangsu Key Laboratory of Advanced Functional Polymer Design and ApplicationSoochow UniversitySuzhou 215123 China) Fax: (+86)?512–65880098;</p> <p>Biomedical Polymers Laboratory and Jiangsu Key Laboratory of Advanced Functional Polymer Design and ApplicationSoochow UniversitySuzhou 215123 China) Fax: (+86)?512–65880098;</p> <p>Biomedical Polymers Laboratory and Jiangsu Key Laboratory of Advanced Functional Polymer Design and ApplicationSoochow UniversitySuzhou 215123 China) Fax: (+86)?512–65880098;</p> <p>Biomedical Polymers Laboratory and Jiangsu Key Laboratory of Advanced Functional Polymer Design and ApplicationSoochow UniversitySuzhou 215123 China) Fax: (+86)?512–65880098;</p> <p>Biomedical Polymers Laboratory and Jiangsu Key Laboratory of Advanced Functional Polymer Design and ApplicationSoochow UniversitySuzhou 215123 China) Fax: (+86)?512–65880098;</p> <p>Biomedical Polymers Laboratory and Jiangsu Key Laboratory of Advanced Functional Polymer Design and ApplicationSoochow UniversitySuzhou 215123 China) Fax: (+86)?512–65880098;</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/1186.html" title="物理化学（理论化学）、化学物理学">物理化学（理论化学）、化学物理学;</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=cancer therapy&option=203" rel="nofollow">cancer therapy;</a> <a style="color: #3E7FEB;" href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=doxorubicin&option=203" rel="nofollow">doxorubicin;</a> <a style="color: #3E7FEB;" href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=micelles&option=203" rel="nofollow">micelles;</a> <a style="color: #3E7FEB;" href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=polypeptides&option=203" rel="nofollow">polypeptides;</a> <a style="color: #3E7FEB;" href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=targeted delivery&option=203" rel="nofollow">targeted delivery;</a> </p> <div class="translation"> 机译：癌症疗法;多柔比星;胶束;多肽;目标交付; </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/0704022115624.html">Integrated Multifunctional Micelles Co‐Self‐Assembled from Polypeptides Conjugated with Natural Ferulic Acid and Lipoic Acid for Doxorubicin Delivery</a> <b>[J]</b> . <span> <a href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=Chen 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