氧化应激放大和抗氧化防御破坏的工程纳米药物增强癌症治疗。

IF 6.8 1区 医学 Q1 CHEMISTRY, MEDICINAL
Xiaoya Wu, Jianxin Rong, Yingjian Cui, Jiahui Cong, Xiongwei Qu and Xiuli Hu*, 
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引用次数: 0

摘要

由于肿瘤缺氧和抗氧化防御,光动力疗法(PDT)面临局限性。本文通过一步共组装策略,开发了一种模块化药物输送系统(P@Ce6/PTX),该系统集成了光敏剂(Ce6)、金属离子(Cu2+)和缺氧激活的紫杉醇前药(PTX- mtz),以放大氧化应激诱导的铁凋亡,同时使缺氧触发的化疗成为可能。Cu2+-咪唑配位不仅可以稳定纳米结构,还可以通过改变聚合物与金属的比例实现可控的尺寸调节。Ce6在激光照射下产生细胞毒性ROS,诱导DNA损伤,同时加重缺氧,导致PTX-MTZ减少和PTX/MTZ释放。MTZ消耗NADPH或谷胱甘肽,通过抑制DNA修复使PDT敏感,并加重抗氧化系统。所报道的多调节纳米药物表现出时空可控的PDT,通过脂质过氧化和缺氧激活化疗,Cu2+扩增的铁上坠,肿瘤消退率达到92.3%,脱靶毒性最小。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Engineering Nanomedicine with Oxidative Stress Amplification and Antioxidant Defense Disruption for Enhanced Cancer Treatment

Engineering Nanomedicine with Oxidative Stress Amplification and Antioxidant Defense Disruption for Enhanced Cancer Treatment

Photodynamic therapy (PDT) faces limitations due to tumor hypoxia and antioxidant defenses. Herein, a modular drug delivery system (P@Ce6/PTX) that integrates photosensitizer (Ce6), metal ion (Cu2+), and hypoxia-activated paclitaxel prodrugs (PTX-MTZ) was developed by a one-step coassembly strategy to amplify oxidative stress-induced ferroptosis while enabling hypoxia-triggered chemotherapy. The Cu2+-imidazole coordination not only stabilizes the nanostructure but also facilitates controllable size modulation by varying the polymer-to-metal ratio. Upon laser irradiation, Ce6 generates cytotoxic ROS to induce DNA damage while exacerbating hypoxia, which triggers PTX-MTZ reduction and PTX/MTZ release. MTZ consumes NADPH or GSH to sensitize PDT via inhibiting DNA repair and aggravates the antioxidant system. The reported multimodulating nanomedicine exhibits spatiotemporal controllable PDT, Cu2+-amplified ferroptosis through lipid peroxidation, and hypoxia-activated chemotherapy, achieving 92.3% tumor regression rate with minimal off-target toxicity.

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来源期刊
Journal of Medicinal Chemistry
Journal of Medicinal Chemistry 医学-医药化学
CiteScore
4.00
自引率
11.00%
发文量
804
审稿时长
1.9 months
期刊介绍: The Journal of Medicinal Chemistry is a prestigious biweekly peer-reviewed publication that focuses on the multifaceted field of medicinal chemistry. Since its inception in 1959 as the Journal of Medicinal and Pharmaceutical Chemistry, it has evolved to become a cornerstone in the dissemination of research findings related to the design, synthesis, and development of therapeutic agents. The Journal of Medicinal Chemistry is recognized for its significant impact in the scientific community, as evidenced by its 2022 impact factor of 7.3. This metric reflects the journal's influence and the importance of its content in shaping the future of drug discovery and development. The journal serves as a vital resource for chemists, pharmacologists, and other researchers interested in the molecular mechanisms of drug action and the optimization of therapeutic compounds.
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