Isoliquiritigenin-Loaded Platinum(IV) Prodrug Micelles Induce Sustained Endoplasmic Reticulum Stress for Promoting Cisplatin Chemosensitivity in Ovarian Cancer

IF 8.7 1区化学 Q1 MATERIALS SCIENCE, MULTIDISCIPLINARY ACS Materials Letters Pub Date : 2024-10-31 DOI:10.1021/acsmaterialslett.4c01192

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*,

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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.

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载异硫利尿素铂（IV）前药胶束诱导持续内质网应激促进卵巢癌顺铂化疗敏感性

铂类化疗是卵巢癌（OC）治疗的基石。然而，药物细胞浓度降低、谷胱甘肽（GSH）介导的药物失活和严重的毒副作用是其临床化疗失败的原因。顺铂具有诱导OC内质网应激（ERS）产生的能力，持续的ERS可增强化疗的细胞毒性作用。本研究制备了铂（IV）前药纳米颗粒（IPD NPs）作为异异黄酮原素（ISL，中药）的纳米载体，具有氧化还原响应降解特性和协同ERS扩增，用于增强OC治疗。值得注意的是，IPD NPs含有二十二碳六烯酸（DHA），可以增强细胞摄取并产生活性氧（ROS），从而打破氧化还原稳态，进一步增强ERS的作用。目前，持续ERS扩增用于增强顺铂化疗的策略克服了低细胞摄取，gsh介导的药物解毒，避免了顺铂的剂量依赖性肾毒性，并有望用于OC治疗。

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来源期刊

ACS Materials Letters MATERIALS SCIENCE, MULTIDISCIPLINARY-

CiteScore

14.60

自引率

3.50%

发文量

261

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.

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