{"title":"Isoliquiritigenin-Loaded Platinum(IV) Prodrug Micelles Induce Sustained Endoplasmic Reticulum Stress for Promoting Cisplatin Chemosensitivity in Ovarian Cancer","authors":"Xin Yang, Yan Qiu, Feng Fang, Zhou Cao, Huijiao Fu, Xiaoyan Chen, Jinxiu Tan, Lijuan He, Yu Zhang, Minhong Luo, Wenjia Zhang*, Zhiqiang Yu* and Xuefeng Wang*, ","doi":"10.1021/acsmaterialslett.4c0119210.1021/acsmaterialslett.4c01192","DOIUrl":null,"url":null,"abstract":"<p >Platinum-based chemotherapy is the cornerstone of ovarian cancer (OC) treatment. However, decrease of cellular concentration of the drug, glutathione (GSH)-mediated drug inactivation, and severe toxic side effects contribute to its clinical chemotherapy failure. Cisplatin has the ability to induce endoplasmic reticulum stress (ERS) production in OC, and sustained ERS can potentiate the cytotoxic effects of chemotherapy. Herein, platinum(IV) prodrug nanoparticles (IPD NPs) are prepared as nanocarriers of isoliquiritigenin (ISL, traditional Chinese medicine) with redox-responsive degradation properties and synergistic ERS amplification for enhanced OC treatment. Notably, IPD NPs contain docosahexaenoic acid (DHA) which enhanced cellular uptake as well as generated reactive oxygen species (ROS), thereby breaking redox homeostasis and further augmenting the effect of ERS. This current strategy of sustained ERS amplification for enhanced cisplatin-based chemotherapy overcomes the low cellular uptake, GSH-mediated drug detoxification, avoids the dose-dependent nephrotoxicity of cisplatin, and is promising for OC treatment.</p>","PeriodicalId":19,"journal":{"name":"ACS Materials Letters","volume":"6 12","pages":"5275–5284 5275–5284"},"PeriodicalIF":9.6000,"publicationDate":"2024-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"ACS Materials Letters","FirstCategoryId":"92","ListUrlMain":"https://pubs.acs.org/doi/10.1021/acsmaterialslett.4c01192","RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"MATERIALS SCIENCE, MULTIDISCIPLINARY","Score":null,"Total":0}
引用次数: 0
Abstract
Platinum-based chemotherapy is the cornerstone of ovarian cancer (OC) treatment. However, decrease of cellular concentration of the drug, glutathione (GSH)-mediated drug inactivation, and severe toxic side effects contribute to its clinical chemotherapy failure. Cisplatin has the ability to induce endoplasmic reticulum stress (ERS) production in OC, and sustained ERS can potentiate the cytotoxic effects of chemotherapy. Herein, platinum(IV) prodrug nanoparticles (IPD NPs) are prepared as nanocarriers of isoliquiritigenin (ISL, traditional Chinese medicine) with redox-responsive degradation properties and synergistic ERS amplification for enhanced OC treatment. Notably, IPD NPs contain docosahexaenoic acid (DHA) which enhanced cellular uptake as well as generated reactive oxygen species (ROS), thereby breaking redox homeostasis and further augmenting the effect of ERS. This current strategy of sustained ERS amplification for enhanced cisplatin-based chemotherapy overcomes the low cellular uptake, GSH-mediated drug detoxification, avoids the dose-dependent nephrotoxicity of cisplatin, and is promising for OC treatment.
期刊介绍:
ACS Materials Letters is a journal that publishes high-quality and urgent papers at the forefront of fundamental and applied research in the field of materials science. It aims to bridge the gap between materials and other disciplines such as chemistry, engineering, and biology. The journal encourages multidisciplinary and innovative research that addresses global challenges. Papers submitted to ACS Materials Letters should clearly demonstrate the need for rapid disclosure of key results. The journal is interested in various areas including the design, synthesis, characterization, and evaluation of emerging materials, understanding the relationships between structure, property, and performance, as well as developing materials for applications in energy, environment, biomedical, electronics, and catalysis. The journal has a 2-year impact factor of 11.4 and is dedicated to publishing transformative materials research with fast processing times. The editors and staff of ACS Materials Letters actively participate in major scientific conferences and engage closely with readers and authors. The journal also maintains an active presence on social media to provide authors with greater visibility.