金纳米笼探针用于线粒体成像和光热损伤细胞★
收稿日期: 2023-05-12
网络出版日期: 2023-07-21
基金资助
国家自然科学基金(22276102); 泰山学者工程(tsqn202211212); 山东省自然科学基金(ZR2023JQ004); 山东省自然科学基金(ZR2022MB024); 济南市引进创新团队(202228027); 山东省高等学校青创科技计划创新团队(2020KJC003); 齐鲁工业大学(山东省科学院)科教产融合试点工程项目(2023PYI002)
Au Nanocages Probes for Mitochondrial Imaging and Photothermal Damage Cells★
Received date: 2023-05-12
Online published: 2023-07-21
Supported by
National Natural Science Foundation of China(22276102); Young Taishan Scholar Program of Shandong Province of China(tsqn202211212); Shandong Provincial Natural Science Foundation(ZR2023JQ004); Shandong Provincial Natural Science Foundation(ZR2022MB024); University Institute Innovation Team of Jinan(202228027); Development Plan of Youth Innovation Team in Colleges and Universities of Shandong Province(2020KJC003); Science, Education and Industry Integration Pilot Project Plan of Qilu University of Technology (Shandong Academy of Sciences)(2023PYI002)
线粒体是许多细胞行为的关键调节细胞器, 线粒体膜电位降低被认为是细胞凋亡所发生的最早事件之一, 因此线粒体成像及其膜电位的检测分析, 对疾病的检测与治疗有重要的科学意义. 采用金纳米笼(Au nanocages, AuNCs)介导的光热损伤与温度敏感的药物释放相结合, 开发了一种线粒体靶向的荧光纳米探针AuNCs/PLEL/JC/KLA. 引入一种线粒体靶向肽(KLAKLAKKLAKLAK, KLA), 作为纳米探针的“指向标”, 指引着探针特异地靶向到细胞线粒体部位, 随后在近红外光的照射下, AuNCs吸收光能转化为热量, 实现光热介导的细胞损伤. 同时, 高温促使外层温敏水凝胶发生凝胶-溶胶转变, 实现荧光染料(JC-10)的释放. 所释放的JC-10荧光染料可根据线粒体的活力表现出两种荧光信号, 用于监测线粒体膜电位的变化. 总之, 该荧光纳米探针不仅实现了线粒体靶向的荧光成像与损伤细胞, 同时还可以监测线粒体膜电位的变化.
孙丽 , 王亚静 , 李涛 , 郭英姝 , 张书圣 . 金纳米笼探针用于线粒体成像和光热损伤细胞★[J]. 化学学报, 2023 , 81(10) : 1301 -1310 . DOI: 10.6023/A23050222
Mitochondria are the key regulatory organelles of many cell behaviors, and the reduction of mitochondrial membrane potential is considered to be one of the earliest events of cell apoptosis. Therefore, mitochondrial imaging and the detection and analysis of mitochondrial membrane potential are of great scientific significance for the detection and treatment of diseases. In this work, AuNCs/PLEL/JC/KLA, a mitochondrial targeted fluorescent nanoprobe, was developed using Au nanocages (AuNCs) mediated photothermal damage combined with temperature-sensitive drug release. At the same time, the temperature-sensitive hydrogel poly(d,l-lactide)-poly(ethylene glycol)-poly(d,l-lactide) (PDLLA-PEG-PDLLA, PLEL) is used as the outer structure to control the release. A mitochondrial targeting peptide (KLAKLAKKLAKLAK, KLA) was introduced as the "pointer" of the nanoprobe to specifically target the mitochondria. The colocalization experiment showed that the nanoprobe was highly colocalized with mitochondria, indicating that the nanoprobe was selectively enriched in mitochondria. It is worth noting that the nanoprobe has excellent photothermal properties, and its photothermal conversion efficiency can be as high as 39.11%. Therefore, under the irradiation of near infrared light, the probe can absorb light energy into heat. Subsequently, the results of Cell Counting Kit 8 (CCK-8) confirmed that the nanoprobes could achieve local photothermal damage at mitochondrial sites, triggering high temperature mediated mitochondrial dysfunction and inducing apoptosis of cancer cells. Meanwhile, rheological analysis and fluorescence curve showed that high temperature promotes the gel-sol transformation of PLEL thermosensitive hydrogel and realizes the release of fluorescent dye (JC-10). The confocal images of the cells showed that the released JC-10 fluorescent dye can display red and green fluorescence signals based on mitochondrial activity. In conclusion, the fluorescence nanoprobe can not only achieve mitochondrial targeted fluorescence imaging and damage cells, but also monitor the changes of mitochondrial membrane potential.
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