线粒体硫化蛋白向的共价不动化促进高效的铜(II) 耗尽用于增强癌症治疗
Zhongsheng Zhao1, Yuqi Zhang1, Yurong Fan2
1State Key Laboratory of Radiation Medicine and Protection, School for Radiological and Interdisciplinary Sciences (RAD-X) and Collaborative Innovation Center of Radiation Medicine of Jiangsu Higher Education Institutions, Soochow University, Suzhou 215123, P. R. China.
ACS applied materials & interfaces
|September 18, 2024
概括
研究人员开发了一种新型探针d-IR-DPA,用于在三阴性乳腺癌 (TNBC) 中可视化和耗尽线粒体铜. 这种方法针对铜 (II) 诱导氧化应激并抑制TNBC瘤生长 in vivo.
科学领域:
- 生物医学工程 生物医学工程
- 癌症研究 癌症研究
- 分子成像学分子成像学
背景情况:
- 铜对于细胞代谢和氧化应激至关重要.
- 线粒体铜失调与三阴性乳腺癌 (TNBC) 有关.
- 同时可视化和线粒体铜的耗尽是TNBC诊断和治疗的挑战.
研究的目的:
- 开发和评估一种新的线粒体可 anchorable 探头,d-IR-DPA,用于同时可视化和耗尽线粒体铜.
- 评估探针对内铜的定量光声学成像和体内抗TNBC治疗的潜力.
主要方法:
- 设计和合成了d-IR-DPA,这是一种具有共价固定能力的线粒体向探针.
- 使用比度光声成像 (PA680 nm/PA800 nm) 来定量检测瘤中的Cu2+水平.
- 研究了探针对TNBC细胞和体内模型中氧化应激,线粒体损伤,亡和代谢途径的影响.
主要成果:
- d-IR-DPA通过光声学成像实现了内Cu2+的定量可视化.
- 该探测器有效地清除了线粒体Cu2 +,诱导了氧化应激,线粒体损伤和TNBC细胞亡.
- 通过d-IR-DPA消耗Cu2+将细胞代谢从氧化酸化转变为糖解,在体内抑制了TNBC瘤的生长.
结论:
- 新的d-IR-DPA探针提供了一个强大的工具,用于同时对线粒体铜的可视化和消耗在TNBC.
- 这一策略通过诱导代谢重编程和亡,显示出有效的TNBC治疗的巨大潜力.
- 该探针也可能对治疗其他与铜相关的疾病有价值.
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