• 文献检索
  • 文档翻译
  • 深度研究
  • 学术资讯
  • Suppr Zotero 插件Zotero 插件
  • 邀请有礼
  • 套餐&价格
  • 历史记录
应用&插件
Suppr Zotero 插件Zotero 插件浏览器插件Mac 客户端Windows 客户端微信小程序
定价
高级版会员购买积分包购买API积分包
服务
文献检索文档翻译深度研究API 文档MCP 服务
关于我们
关于 Suppr公司介绍联系我们用户协议隐私条款
关注我们

Suppr 超能文献

核心技术专利：CN118964589B侵权必究
粤ICP备2023148730 号-1Suppr @ 2026

文献检索

告别复杂PubMed语法，用中文像聊天一样搜索，搜遍4000万医学文献。AI智能推荐，让科研检索更轻松。

立即免费搜索

文件翻译

保留排版，准确专业，支持PDF/Word/PPT等文件格式，支持 12+语言互译。

免费翻译文档

深度研究

AI帮你快速写综述，25分钟生成高质量综述，智能提取关键信息，辅助科研写作。

立即免费体验

杂环卡宾-铱配合物作为光敏剂用于体外光动力疗法以诱导癌细胞发生非细胞凋亡性死亡。

-Heterocyclic Carbene-Iridium Complexes as Photosensitizers for In Vitro Photodynamic Therapy to Trigger Non-Apoptotic Cell Death in Cancer Cells.

机构信息

Coordination Chemistry Laboratory of the National Centre for Scientific Research (LCC-CNRS), University of Toulouse, CNRS, Université Toulouse III-Paul Sabatier (UPS), 31077 Toulouse, France.

Institut de Pharmacologie et de Biologie Structurale (IPBS), Université de Toulouse, CNRS, Université Toulouse III-Paul Sabatier (UPS), 31077 Toulouse, France.

出版信息

Molecules. 2023 Jan 10;28(2):691. doi: 10.3390/molecules28020691.

DOI:10.3390/molecules28020691
PMID:36677751
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9861386/
Abstract

A series of seven novel iridium complexes were synthetized and characterized as potential photosensitizers for photodynamic therapy (PDT) applications. Among them, four complexes were evaluated in vitro for their anti-proliferative activity with and without irradiation on a panel of five cancer cell lines, namely PC-3 (prostate cancer), T24 (bladder cancer), MCF7 (breast cancer), A549 (lung cancer) and HeLa (cervix cancer), and two non-cancerous cell models (NIH-3T3 fibroblasts and MC3T3 osteoblasts). After irradiation at 458 nm, all tested complexes showed a strong selectivity against cancer cells, with a selectivity index (SI) ranging from 8 to 34 compared with non-cancerous cells. The cytotoxic effect of all these complexes was found to be independent of the anti-apoptotic protein Bcl-xL. The compound exhibiting the best selectivity, complex , was selected for further investigations. Complex was mainly localized in the mitochondria. We found that the loss of cell viability and the decrease in ATP and GSH content induced by complex were independent of both Bcl-xL and caspase activation, leading to a non-apoptotic cell death. By counteracting the intrinsic or acquired resistance to apoptosis associated with cancer, complex could be an interesting therapeutic alternative to be studied in preclinical models.

摘要

一系列七种新型铱配合物被合成并表征为潜在的用于光动力疗法（PDT）应用的光敏剂。其中，四种配合物在体外进行了评估，研究了它们在照射和不照射的情况下对五种癌细胞系（前列腺癌 PC-3、膀胱癌 T24、乳腺癌 MCF7、肺癌 A549 和宫颈癌 HeLa）和两种非癌细胞模型（成纤维细胞 NIH-3T3 和成骨细胞 MC3T3）的抗增殖活性。在 458nm 照射后，所有测试的配合物均表现出对癌细胞的强烈选择性，与非癌细胞相比，选择性指数（SI）范围为 8 至 34。发现所有这些配合物的细胞毒性作用均独立于抗凋亡蛋白 Bcl-xL。表现出最佳选择性的化合物 被选为进一步研究。化合物 主要定位于线粒体。我们发现，由配合物 引起的细胞活力丧失和 ATP 和 GSH 含量的降低与 Bcl-xL 和半胱天冬酶激活无关，导致非凋亡性细胞死亡。通过对抗与癌症相关的内在或获得性抗凋亡能力，配合物 可能是一种有前途的治疗选择，可以在临床前模型中进行研究。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/14a2/9861386/3528ade6b548/molecules-28-00691-g015.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/14a2/9861386/36894d8d587d/molecules-28-00691-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/14a2/9861386/885a67085d04/molecules-28-00691-sch001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/14a2/9861386/87fc4a8bb3c6/molecules-28-00691-sch002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/14a2/9861386/2e97c630e17e/molecules-28-00691-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/14a2/9861386/b1d4a10644be/molecules-28-00691-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/14a2/9861386/aab394838e36/molecules-28-00691-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/14a2/9861386/070e3858b371/molecules-28-00691-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/14a2/9861386/ad0af274b6b8/molecules-28-00691-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/14a2/9861386/5d0488550350/molecules-28-00691-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/14a2/9861386/0b734e9260fa/molecules-28-00691-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/14a2/9861386/f0da46228950/molecules-28-00691-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/14a2/9861386/b1c2211d8ef1/molecules-28-00691-g010.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/14a2/9861386/6961682c997f/molecules-28-00691-g011.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/14a2/9861386/561c1b578bf2/molecules-28-00691-g012.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/14a2/9861386/2ae667006c2a/molecules-28-00691-g013.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/14a2/9861386/7cb9e2f98fff/molecules-28-00691-g014.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/14a2/9861386/3528ade6b548/molecules-28-00691-g015.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/14a2/9861386/36894d8d587d/molecules-28-00691-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/14a2/9861386/885a67085d04/molecules-28-00691-sch001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/14a2/9861386/87fc4a8bb3c6/molecules-28-00691-sch002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/14a2/9861386/2e97c630e17e/molecules-28-00691-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/14a2/9861386/b1d4a10644be/molecules-28-00691-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/14a2/9861386/aab394838e36/molecules-28-00691-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/14a2/9861386/070e3858b371/molecules-28-00691-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/14a2/9861386/ad0af274b6b8/molecules-28-00691-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/14a2/9861386/5d0488550350/molecules-28-00691-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/14a2/9861386/0b734e9260fa/molecules-28-00691-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/14a2/9861386/f0da46228950/molecules-28-00691-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/14a2/9861386/b1c2211d8ef1/molecules-28-00691-g010.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/14a2/9861386/6961682c997f/molecules-28-00691-g011.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/14a2/9861386/561c1b578bf2/molecules-28-00691-g012.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/14a2/9861386/2ae667006c2a/molecules-28-00691-g013.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/14a2/9861386/7cb9e2f98fff/molecules-28-00691-g014.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/14a2/9861386/3528ade6b548/molecules-28-00691-g015.jpg

相似文献

1
-Heterocyclic Carbene-Iridium Complexes as Photosensitizers for In Vitro Photodynamic Therapy to Trigger Non-Apoptotic Cell Death in Cancer Cells.杂环卡宾-铱配合物作为光敏剂用于体外光动力疗法以诱导癌细胞发生非细胞凋亡性死亡。
Molecules. 2023 Jan 10;28(2):691. doi: 10.3390/molecules28020691.
2
Metal Complexes for Two-Photon Photodynamic Therapy: A Cyclometallated Iridium Complex Induces Two-Photon Photosensitization of Cancer Cells under Near-IR Light.用于双光子光动力疗法的金属配合物：一种环金属化铱配合物在近红外光下诱导癌细胞的双光子光敏化。
Chemistry. 2017 Jan 5;23(2):234-238. doi: 10.1002/chem.201604792. Epub 2016 Nov 2.
3
Recent Advances in the Design of Targeted Iridium(III) Photosensitizers for Photodynamic Therapy.靶向铱(III)光敏剂用于光动力疗法的设计研究进展。
Chembiochem. 2018 Aug 6;19(15):1574-1589. doi: 10.1002/cbic.201800182. Epub 2018 Jul 18.
4
Synthesis, photophysical and anticancer properties of mitochondria-targeted phosphorescent cyclometalated iridium(III) N-heterocyclic carbene complexes.线粒体靶向磷光金属铱(III) N-杂环卡宾配合物的合成、光物理性质及抗癌活性。
J Inorg Biochem. 2020 Apr;205:110976. doi: 10.1016/j.jinorgbio.2019.110976. Epub 2019 Dec 27.
5
Rational Design of Phosphorescent Iridium(III) Complexes for Selective Glutathione Sensing and Amplified Photodynamic Therapy.理性设计用于选择性谷胱甘肽传感和放大光动力治疗的磷光铱（III）配合物。
Chembiochem. 2019 Feb 15;20(4):576-586. doi: 10.1002/cbic.201800507. Epub 2018 Nov 8.
6
Mitochondria-targeted iridium-based photosensitizers enhancing photodynamic therapy effect by disturbing cellular redox balance.线粒体靶向铱基光敏剂通过扰乱细胞氧化还原平衡增强光动力治疗效果。
Free Radic Biol Med. 2023 Feb 1;195:121-131. doi: 10.1016/j.freeradbiomed.2022.12.091. Epub 2022 Dec 26.
7
Photodynamic therapy of prostate cancer using porphyrinic formulations.使用卟啉制剂对前列腺癌进行光动力治疗。
J Photochem Photobiol B. 2021 Oct;223:112301. doi: 10.1016/j.jphotobiol.2021.112301. Epub 2021 Aug 26.
8
Two near-infrared phosphorescent iridium(III) complexes for the detection of GSH and photodynamic therapy.两种近红外磷光铱（III）配合物用于检测 GSH 和光动力疗法。
Dalton Trans. 2023 Sep 26;52(37):13137-13145. doi: 10.1039/d3dt01826a.
9
Halogen-bridged binuclear iridium(III) complexes with enhanced photodynamic therapeutic effects in mitochondria.具有增强线粒体光动力治疗效果的卤素桥联双核铱(III)配合物。
J Mater Chem B. 2022 Aug 24;10(33):6307-6314. doi: 10.1039/d2tb01078j.
10
Rational design of mitochondria targeted thiabendazole-based Ir(III) biscyclometalated complexes for a multimodal photodynamic therapy of cancer.基于噻苯达唑的 Ir(III)双环金属配合物的线粒体靶向理性设计用于癌症的多模式光动力治疗。
J Inorg Biochem. 2022 Jun;231:111790. doi: 10.1016/j.jinorgbio.2022.111790. Epub 2022 Mar 14.

本文引用的文献

1
Iridium(iii) complexes as mitochondrial topoisomerase inhibitors against cisplatin-resistant cancer cells.铱(III)配合物作为线粒体拓扑异构酶抑制剂对抗顺铂耐药癌细胞。
Chem Commun (Camb). 2021 Aug 28;57(67):8308-8311. doi: 10.1039/d1cc02178h. Epub 2021 Jul 28.
2
Phosphorescent metal complexes as theranostic anticancer agents: combining imaging and therapy in a single molecule.磷光金属配合物作为诊疗一体化抗癌剂：在单个分子中结合成像与治疗
Chem Sci. 2021 Jan 27;12(7):2357-2367. doi: 10.1039/d0sc06885c.
3
Enhancing the ROS generation ability of a rhodamine-decorated iridium(iii) complex by ligand regulation for endoplasmic reticulum-targeted photodynamic therapy.
通过配体调控增强罗丹明修饰的铱（III）配合物的活性氧生成能力用于内质网靶向光动力治疗
Chem Sci. 2020 Oct 12;11(44):12212-12220. doi: 10.1039/d0sc04751a.
4
A new near-infrared phosphorescent iridium(III) complex conjugated to a xanthene dye for mitochondria-targeted photodynamic therapy.一种新型近红外磷光铱(III)配合物与香豆素染料偶联，用于线粒体靶向光动力疗法。
Biomater Sci. 2021 Jul 13;9(14):4843-4853. doi: 10.1039/d1bm00128k.
5
Cancer statistics for the year 2020: An overview.2020年癌症统计数据概述。
Int J Cancer. 2021 Apr 5. doi: 10.1002/ijc.33588.
6
Ferroptosis Photoinduced by New Cyclometalated Iridium(III) Complexes and Its Synergism with Apoptosis in Tumor Cell Inhibition.新型金属环铱(III)配合物光诱导的铁死亡及其对肿瘤细胞抑制的凋亡协同作用。
Angew Chem Int Ed Engl. 2021 Apr 6;60(15):8174-8181. doi: 10.1002/anie.202014959. Epub 2021 Mar 3.
7
Unveiling the Potential of Transition Metal Complexes for Medicine: Translational in Situ Activation of Metal-Based Drugs from Bench to in Vivo Applications.揭示过渡金属配合物在医学中的潜力：从实验室到体内应用的基于金属药物的转化原位激活。
Chembiochem. 2021 May 14;22(10):1740-1742. doi: 10.1002/cbic.202100015. Epub 2021 Feb 25.
8
Exploring anticancer efficiency of mitochondria-targeted cyclometalated iridium(III) complexes.探究靶向线粒体的金属铱（III）配合物的抗癌效率。
J Inorg Biochem. 2020 Nov;212:111215. doi: 10.1016/j.jinorgbio.2020.111215. Epub 2020 Aug 8.
9
Combining PARP Inhibition with Platinum, Ruthenium or Gold Complexes for Cancer Therapy.联合 PARP 抑制剂与铂、钌或金配合物用于癌症治疗。
ChemMedChem. 2020 Nov 18;15(22):2121-2135. doi: 10.1002/cmdc.202000391. Epub 2020 Sep 10.
10
Mitochondria-targeted artesunate conjugated cyclometalated iridium(iii) complexes as potent anti-HepG2 hepatocellular carcinoma agents.线粒体靶向青蒿琥酯键合金属铱(III)配合物作为有效的抗 HepG2 肝癌药物。
Metallomics. 2020 Jul 22;12(7):1131-1141. doi: 10.1039/d0mt00060d.