用等离子体荧光纳米探针监测热疗细胞凋亡过程中核仁形态和 ATP 含量变化的应激反应差异,Analytical Chemistry

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用等离子体荧光纳米探针监测热疗细胞凋亡过程中核仁形态和 ATP 含量变化的应激反应差异
Analytical Chemistry ( IF 6.7 ) Pub Date : 2022-09-29 , DOI: 10.1021/acs.analchem.2c02464
Xin Guan ₁ , Bo Wang ₂ , Ying Zhang _{2,

3} , Guohua Qi ₂ , Limei Chen ₁ , Yongdong Jin _{2,

3}

Affiliation

核仁作为主要的“细胞应激受体”，是应激反应驱动癌症发展的中枢，在细胞器靶向光热治疗领域具有重要的研究价值。然而，很少有研究专注于监测核仁应激反应并揭示光热治疗期间细胞的能量代谢如何调节核仁应激反应。在此，通过设计基于金纳米棒 (AuNRs) 和荧光碳量子点 (CDs) 的核仁靶向和 ATP 和光热响应等离子体荧光纳米探针 (AuNRs-CDs)，我们实现了核形态的实时荧光成像，同时在亚细胞水平监测 ATP 含量的变化。我们发现绿色荧光在光热治疗 5 分钟后减弱，并且癌变HepG2细胞中的核仁形态开始缩小并变小。相反，正常HL-7702细胞的核仁区绿色荧光没有明显变化。ATP 含量监测也显示出类似的结果。显然，与正常细胞相比，在高温诱导的细胞凋亡下，与正常细胞相比，癌细胞在光热刺激下产生更多的ATP（能量），并且核仁形态和状态发生明显变化。开发的 AuNRs-CDs 作为核仁成像纳米探针和有效的光热剂在核仁应力研究和靶向光热治疗方面具有广阔的应用前景。ATP 含量监测也显示出类似的结果。显然，与正常细胞相比，在高温诱导的细胞凋亡下，与正常细胞相比，癌细胞在光热刺激下产生更多的ATP（能量），并且核仁形态和状态发生明显变化。开发的 AuNRs-CDs 作为核仁成像纳米探针和有效的光热剂在核仁应力研究和靶向光热治疗方面具有广阔的应用前景。ATP 含量监测也显示出类似的结果。显然，与正常细胞相比，在高温诱导的细胞凋亡下，与正常细胞相比，癌细胞在光热刺激下产生更多的ATP（能量），并且核仁形态和状态发生明显变化。开发的 AuNRs-CDs 作为核仁成像纳米探针和有效的光热剂在核仁应力研究和靶向光热治疗方面具有广阔的应用前景。

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Monitoring Stress Response Difference in Nucleolus Morphology and ATP Content Changes during Hyperthermia Cell Apoptosis with Plasmonic Fluorescent Nanoprobes

The nucleolus, as a main “cellular stress receptor”, is the hub of the stress response driving cancer development and has great research value in the field of organelle-targeting photothermal therapy. However, there are few studies focused on monitoring nucleolar stress response and revealing how the energy metabolism of cells regulates the nucleolar stress response during photothermal therapy. Herein, by designing a nucleolus-targeting and ATP- and photothermal-responsive plasmonic fluorescent nanoprobe (AuNRs-CDs) based on gold nanorods (AuNRs) and fluorescent carbon quantum dots (CDs), we achieved real-time fluorescence imaging of nucleus morphology while monitoring changes of ATP content at the subcellular level. We found that the green fluorescence diminished at 5 min of photothermal therapy, and the nucleolus morphology began to shrink and became smaller in cancerous HepG2 cells. In contrast, there is no significant change of green fluorescence in the nucleolar region of normal HL-7702 cells. ATP content monitoring also showed similar results. Apparently, in response to photothermal stimuli, cancerous cells produce more ATP (energy) along with obvious change in nucleolus morphology and state compared to normal cells under the hyperthermia-induced cell apoptosis. The developed AuNRs-CDs as a nucleolus imaging nanoprobe and effective photothermal agent present promising applications for nucleolar stress studies and targeted photothermal therapy.

更新日期：2022-09-29

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