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。

IF 5.7 3区 医学 Q1 MATERIALS SCIENCE, BIOMATERIALS
Jianrong Cao, Keze Hong, Chengqi Lv, Weiting Jiang, Qi Chen, Rongze Wang and Yong Wang
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引用次数: 0

摘要

肝细胞癌(HCC)是最致命的恶性肿瘤之一,因此亟需开发针对 HCC 的有效疗法。一种新型喹唑啉衍生物 04NB-03(Qd04)已被证实对 HCC 非常有效,且无明显毒副作用。然而,水溶性差、体内生物利用度低等问题严重限制了它的临床应用。此外,Qd04通过诱导内源性活性氧(ROS)的积累来杀死肿瘤细胞,而肿瘤细胞中谷胱甘肽(GSH)的过度表达会严重阻碍ROS的积累。在此,我们设计了一种二硫交联聚氨基酸胶束,用于递送 Qd04 治疗 HCC。二硫连接不仅能通过响应肿瘤细胞的谷胱甘肽实现Qd04的肿瘤靶向递送,还能消耗谷胱甘肽以增加ROS的生成水平,从而提高Qd04的治疗效率。体外和体内实验结果均表明,合成的纳米药物具有良好的抗肝癌效果,有望应用于临床治疗 HCC。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Reduction-sensitive polymeric carrier for the targeted delivery of a quinazoline derivative for enhanced generation of reactive oxygen species against cancer†

Reduction-sensitive polymeric carrier for the targeted delivery of a quinazoline derivative for enhanced generation of reactive oxygen species against cancer†

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.

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来源期刊
Biomaterials Science
Biomaterials Science MATERIALS SCIENCE, BIOMATERIALS-
CiteScore
11.50
自引率
4.50%
发文量
556
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.
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