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利用瘤微环境来增强协同光动力学疗法,基于功能性的铁死抗瘤效率 (III) 复合物

Yu Pei^1,2, Yinzhen Pan², Zhijun Zhang²

¹Key Laboratory of Nanobiosensing and Nanobioanalysis at Universities of Jilin Province, Department of Chemistry, Northeast Normal University, 5268 Renmin Street, Changchun, Jilin Province, 130024, P. R. China.

Advanced science (Weinheim, Baden-Wurttemberg, Germany)

|February 14, 2025

概括

这项研究介绍了Ir-Fc,这是一种利用瘤微环境来增强光动力学疗法 (PDT) 和癌症治疗中的ferroptosis的新药. 伊尔-Fc克服了缺氧和谷氨抑制,为协同瘤治疗提供了一种革命性的方法.

科学领域:

生物医学工程生物医学工程
材料科学材料科学材料科学
在瘤学瘤学.

背景情况:

瘤微环境 (TME) 对光动力学疗法 (PDT) 的有效性提出了重大挑战,原因是缺氧和高谷氨 (GSH) 水平.
开发可以协同利用TME增强抗瘤活性的药物对于推进癌症治疗至关重要.

研究的目的:

设计和合成一种新的小分子剂,Ir-Fc,能够通过克服TME相关的局限性来成像和治疗瘤.
研究将PDT与ferroptosis诱导相结合的协同潜力,利用TME来提高治疗结果.

主要方法:

一个 (III) - 铁复合物 (Ir-Fc) 通过一种 imine 键构建,旨在在 lysosomes 中分裂.
分解产物Fc-CHO和Ir-NH2被分析为它们在芬顿反应,铁灭菌诱导和活性氧物种 (ROS) 生成中的作用.
评估了铁亡途径对TME内的GSH消耗和氧气生产的影响.

主要成果:

溶解体裂变的Ir-Fc破坏了光诱导电子转移 (PET) 并产生了Fc-CHO和Ir-NH2.
Fc-CHO启动了芬顿反应以产生基基 (•OH),在黑暗条件下诱导铁亡.
伊尔-NH2有效地产生了I型和II型反应性氧物种 (ROS),而铁化途径消耗了GSH并产生了O2,缓解了瘤缺氧.

结论:

通过有效利用TME,Ir-Fc展示了协同瘤治疗的新策略.
该药物能够诱导铁和PDT,同时抵消TME诱导的耐药性,这为癌症治疗提供了一个有前途的新方案.

关键词:

芬顿反应是芬顿反应的一个反应.铁烯酸铁烯酸铁烯酸铁烯酸是什么铁性化 (ferroptosis) 是一种 (III) 复合物 (III) 复合物光动力学疗法是一种光动力学疗法.

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