Jianrong Cao, Keze Hong, Chengqi Lv, Weiting Jiang, Qi Chen, Rongze Wang and Yong Wang
{"title":"还原敏感聚合物载体,用于靶向输送喹唑啉衍生物,以增强活性氧的抗癌作用。","authors":"Jianrong Cao, Keze Hong, Chengqi Lv, Weiting Jiang, Qi Chen, Rongze Wang and Yong Wang","doi":"10.1039/D3BM02136J","DOIUrl":null,"url":null,"abstract":"<p >Hepatocellular carcinoma (HCC) is one of the deadliest malignant tumors and the development of effective therapeutics against HCC is urgently needed. A novel quinazoline derivative 04NB-03 (Qd04) has been proved to be highly effective against HCC without obvious toxic side-effects. However, the poor water solubility and low bioavailability <em>in vivo</em> severely limit its clinical application. In addition, Qd04 kills tumor cells by inducing an accumulation of endogenous reactive oxygen species (ROS), which is highly impeded by the overexpression of glutathione (GSH) in tumor cells. Herein, we designed a disulfide cross-linked polyamino acid micelle to deliver Qd04 for HCC therapy. The disulfide linkage not only endowed a tumor-targeted delivery of Qd04 by responding to tumor cell GSH but also depleted GSH to achieve increased levels of ROS generation, which improved the therapeutic efficiency of Qd04. Both <em>in vitro</em> and <em>in vivo</em> results demonstrated that the synthesized nanodrug exerted good anti-hepatoma effects, which provided a potential application for HCC therapy in clinics.</p>","PeriodicalId":65,"journal":{"name":"Biomaterials Science","volume":" 10","pages":" 2626-2638"},"PeriodicalIF":5.7000,"publicationDate":"2024-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Reduction-sensitive polymeric carrier for the targeted delivery of a quinazoline derivative for enhanced generation of reactive oxygen species against cancer†\",\"authors\":\"Jianrong Cao, Keze Hong, Chengqi Lv, Weiting Jiang, Qi Chen, Rongze Wang and Yong Wang\",\"doi\":\"10.1039/D3BM02136J\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p >Hepatocellular carcinoma (HCC) is one of the deadliest malignant tumors and the development of effective therapeutics against HCC is urgently needed. A novel quinazoline derivative 04NB-03 (Qd04) has been proved to be highly effective against HCC without obvious toxic side-effects. However, the poor water solubility and low bioavailability <em>in vivo</em> severely limit its clinical application. In addition, Qd04 kills tumor cells by inducing an accumulation of endogenous reactive oxygen species (ROS), which is highly impeded by the overexpression of glutathione (GSH) in tumor cells. Herein, we designed a disulfide cross-linked polyamino acid micelle to deliver Qd04 for HCC therapy. The disulfide linkage not only endowed a tumor-targeted delivery of Qd04 by responding to tumor cell GSH but also depleted GSH to achieve increased levels of ROS generation, which improved the therapeutic efficiency of Qd04. Both <em>in vitro</em> and <em>in vivo</em> results demonstrated that the synthesized nanodrug exerted good anti-hepatoma effects, which provided a potential application for HCC therapy in clinics.</p>\",\"PeriodicalId\":65,\"journal\":{\"name\":\"Biomaterials Science\",\"volume\":\" 10\",\"pages\":\" 2626-2638\"},\"PeriodicalIF\":5.7000,\"publicationDate\":\"2024-03-25\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Biomaterials Science\",\"FirstCategoryId\":\"5\",\"ListUrlMain\":\"https://pubs.rsc.org/en/content/articlelanding/2024/bm/d3bm02136j\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"MATERIALS SCIENCE, BIOMATERIALS\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Biomaterials Science","FirstCategoryId":"5","ListUrlMain":"https://pubs.rsc.org/en/content/articlelanding/2024/bm/d3bm02136j","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"MATERIALS SCIENCE, BIOMATERIALS","Score":null,"Total":0}
Reduction-sensitive polymeric carrier for the targeted delivery of a quinazoline derivative for enhanced generation of reactive oxygen species against cancer†
Hepatocellular carcinoma (HCC) is one of the deadliest malignant tumors and the development of effective therapeutics against HCC is urgently needed. A novel quinazoline derivative 04NB-03 (Qd04) has been proved to be highly effective against HCC without obvious toxic side-effects. However, the poor water solubility and low bioavailability in vivo severely limit its clinical application. In addition, Qd04 kills tumor cells by inducing an accumulation of endogenous reactive oxygen species (ROS), which is highly impeded by the overexpression of glutathione (GSH) in tumor cells. Herein, we designed a disulfide cross-linked polyamino acid micelle to deliver Qd04 for HCC therapy. The disulfide linkage not only endowed a tumor-targeted delivery of Qd04 by responding to tumor cell GSH but also depleted GSH to achieve increased levels of ROS generation, which improved the therapeutic efficiency of Qd04. Both in vitro and in vivo results demonstrated that the synthesized nanodrug exerted good anti-hepatoma effects, which provided a potential application for HCC therapy in clinics.
期刊介绍:
Biomaterials Science is an international high impact journal exploring the science of biomaterials and their translation towards clinical use. Its scope encompasses new concepts in biomaterials design, studies into the interaction of biomaterials with the body, and the use of materials to answer fundamental biological questions.