A Multi‐action and Multi‐target RuII–PtIV Conjugate Combining Cancer‐Activated Chemotherapy and Photodynamic Therapy to Overcome Drug Resistant Cancers

Karges Johannes; Yempala Thirumal; Tharaud Micka?l; Gibson Dan; Gasser Gilles

摘要

Abstract > Pt II complexes are commonly used to treat cancer. To reduce their side effects and improve their pharmacological properties, Pt IV complexes are being developed as prodrug candidates that are activated by reduction in cancer cells. Concomitantly, Ru II polypyridine complexes have gained much attention as photosensitizers for use in photodynamic therapy due to their attractive characteristics. In this article, a novel Pt IV –Ru II conjugate, which combines cancer activated chemotherapy with PDT, is presented. Upon entering the cancer cell, the Pt IV centre is reduced to Pt II and the axial ligands including the Ru II complex and phenylbutyrate are released. As each component has its individual targets, the conjugate exerts a multi‐target and multi‐action effect with (photo‐)cytotoxicity values upon irradiation up to 595?nm in the low nanomolar range in various (drug resistant) 2D monolayer cancer cells and 3D multicellular tumour spheroids. </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> > Pt. ii </ sup> 复合物通常用于治疗癌症。减少副作用，改善其药理学特性，PT iv </ sup> 复合物正在开发成通过减少癌细胞激活的前药候选。克服，ru ii </ sup> 由于其有吸引力的特性，聚吡啶络合物作为光敏剂的光敏剂效应了很多。在本文中，一个小说PT iv </ sup> -ru. ii </ sup> 提出了将癌症活化化疗与PDT结合的缀合物。进入癌细胞后，PT iv </ sup> 中心减少到PT ii </ sup> 和包括ru的轴向配体 ii </ sup> 释放复合物和苯基丁酸酯。当每个组分具有其个体靶标时，缀合物在低至595μm在不同（耐药性）2D单层癌细胞和3D多细胞肿瘤球形。 </ 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18期</span><b style="margin: 0 2px;">|</b><span>共7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=Karges Johannes&option=202" target="_blank" rel="nofollow">Karges Johannes;</a> <a href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=Yempala Thirumal&option=202" target="_blank" rel="nofollow">Yempala Thirumal;</a> <a href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=Tharaud Micka?l&option=202" target="_blank" rel="nofollow">Tharaud Micka?l;</a> <a href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=Gibson Dan&option=202" target="_blank" rel="nofollow">Gibson Dan;</a> <a href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=Gasser Gilles&option=202" target="_blank" rel="nofollow">Gasser Gilles;</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>Chimie ParisTechPSL University75005 Paris France;</p> <p>Institute for Drug ResearchThe Hebrew University of Jerusalem91120 Jerusalem Israel;</p> <p>Institut de Physique du Globe de ParisUniversité de Paris75005 Paris France;</p> <p>Institute for Drug ResearchThe Hebrew University of Jerusalem91120 Jerusalem Israel;</p> <p>Chimie ParisTechPSL University75005 Paris France;</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=bioinorganic chemistry&option=203" rel="nofollow">bioinorganic chemistry;</a> <a style="color: #3E7FEB;" href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=metals in medicine&option=203" rel="nofollow">metals in medicine;</a> <a style="color: #3E7FEB;" href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=photodynamic therapy&option=203" rel="nofollow">photodynamic therapy;</a> <a style="color: #3E7FEB;" href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=platinum prodrugs&option=203" rel="nofollow">platinum prodrugs;</a> </p> <div class="translation"> 机译：生物有机化学;医学中的金属;光动力疗法;铂前药; 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</b><a class="enjiyixqcontent" href="/academic-degree-domestic_mphd_thesis/020313613035.html">化疗药物联合光动力疗法对人宫颈癌Hela细胞杀伤作用的研究</a> <b>[A] </b> <span> <a href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=王兆婧&option=202" target="_blank" rel="nofollow" class="tuijian_auth tuijian_authcolor"> . 王兆婧</a> <span> . 2011</span> </span> </div> </li> </ul> <ul style="display: none;"> <li> <div> <b>1. </b><a class="enjiyixqcontent" href="/patent-detail/06120101546192.html">用于癌症选择性标记和靶向的触发器可激活的糖缀合物</a> <b>[P]</b> . <span> 中国专利： CN110520161A </span> <span> . 2019-11-29</span> </div> </li> <li> <div> <b>2. </b><a class="enjiyixqcontent" href="/patent-detail/06120101481915.html">供治疗癌症的方法中使用的白介素-2免疫缀合物,CD40激动剂,和任选地PD-1轴结合拮抗剂</a> <b>[P]</b> . <span> 中国专利： CN110505883A </span> <span> . 2019-11-26</span> </div> </li> <li> <div> <b>3. </b><a class="enjiyixqcontent" href="/patent-detail/06130409498891.html">cancer growth or a cancer symptom relief method, chemotherapy drug cancer sensitization method, radiotherapy cancer sensitization method, and therapeutic meal package to provide meals for a cancer patient who retards cancer growth and intensifies the effectiveness of chemotherapy drugs</a> <b>[P]</b> . <span> 外国专利：  BR112012009423A2 </span> <span> . 2017-06-13</span> </div> <p class="zwjiyix translation" style="max-width: initial;height: auto;word-break: break-all;white-space: initial;text-overflow: initial;overflow: initial;"> <span>机译：癌症生长或癌症症状缓解方法，化疗药物癌症致敏方法，放疗癌症致敏方法以及治疗性膳食套餐，为癌症患者提供可延缓癌症生长并增强化疗药物有效性的膳食 </span> </p> </li> <li> <div> <b>4. </b><a class="enjiyixqcontent" href="/patent-detail/06130404578356.html">Metabolically-activated drug conjugates to overcome resistance in cancer therapy</a> <b>[P]</b> . <span> 外国专利：  US10300070B2 </span> <span> . 2019-05-28</span> </div> <p class="zwjiyix translation" style="max-width: initial;height: auto;word-break: break-all;white-space: initial;text-overflow: initial;overflow: initial;"> <span>机译：代谢激活的药物结合物可克服癌症治疗中的耐药性 </span> </p> </li> <li> <div> <b>5. </b><a class="enjiyixqcontent" href="/patent-detail/06130408160773.html">METABOLICALLY-ACTIVATED DRUG CONJUGATES TO OVERCOME RESISTANCE IN CANCER THERAPY</a> <b>[P]</b> . <span> 外国专利：  EP3122376A4 </span> <span> . 2017-12-20</span> </div> <p class="zwjiyix translation" style="max-width: initial;height: auto;word-break: break-all;white-space: initial;text-overflow: initial;overflow: initial;"> <span>机译：代谢激活的药物会克服癌症治疗中的耐药性 </span> </p> </li> </ul> </div> </div> </div> <div class="theme cardcommon" style="overflow: auto;display:none"> <h3 class="all_title" id="enpatent55">相关主题</h3> <ul id="subject"> </ul> </div> </div> </div> </div> <div class="right rightcon"> <div class="details_img cardcommon clearfix" style="margin-bottom: 10px;display:none;" > </div> </div> </div> <div id="thesis_get_original1" class="downloadBth" style="bottom: 19px;z-index: 999;" onclick="ywcd('0704028160783','4',7,2,1,'',this,24)" class="delivery" prompt="010401" 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