State Key Laboratory of Analytical Chemistry for Life Science, Chemistry and Biomedicine Innovation Center (ChemBIC), School of Chemistry and Chemical Engineering, Nanjing University, Nanjing 210023, Jiangsu, China.
Institute of Analytical Chemistry, Department of Chemistry, Zhejiang University, Hangzhou 310058, Zhejiang, China.
J Am Chem Soc. 2023 Oct 18;145(41):22433-22441. doi: 10.1021/jacs.3c06085. Epub 2023 Oct 9.
Accurate temperature measurement in one living cell is of great significance for understanding biological functions and regulation. Here, a nanopipet electric thermometer (NET) is established for real-time intracellular temperature measurement. Based on the temperature-controlled ion migration, the temperature change in solution results in altered ion mobilities and ion distributions, which can be converted to the thermoelectric responses of NET in a galvanostatic configuration. The exponential relationship between the voltage and the temperature promises highly sensitive thermoelectric responses up to 11.1 mV K, which is over an order of magnitude higher than previous thermoelectric thermometry. Moreover, the NET exhibits superior thermal resolution of 25 mK and spatiotemporal resolution of 100 nm and 0.9 ms as well as excellent stability and reproducibility. Benefiting from these unique features, both thermal fluctuations in steady-state cells and heat generation and dissipation upon drug administration can be successfully monitored, which are hardly achieved by current methods. By using NET, thermal heterogeneities of single cancer cells during immunotherapy were reported first in this work, in which the increased intracellular temperature was demonstrated to be associated with the survival benefit and resistance of cancer cells in immunotherapy. This work not only provides a reliable method for microscopic temperature monitoring but also gains new insights to elucidate the mechanism of immune evasion and therapeutic resistance.
在单个活细胞中进行准确的温度测量对于理解生物功能和调控具有重要意义。在这里，我们建立了一种纳米管电温度计（NET），用于实时细胞内温度测量。基于温度控制的离子迁移，溶液中的温度变化会导致离子迁移率和离子分布的改变，这些改变可以通过恒电流配置转换为 NET 的热电响应。电压与温度之间的指数关系保证了高达 11.1 mV/K 的高灵敏度热电响应，比以前的热电测温方法高出一个数量级。此外，NET 还具有出色的热分辨率（25 mK）、时空分辨率（100nm 和 0.9ms）以及优异的稳定性和重现性。得益于这些独特的特性，NET 可以成功监测药物作用下细胞的热波动、产热和散热，而这些是目前的方法难以实现的。通过使用 NET，我们首次报道了免疫治疗过程中单癌细胞的热异质性，其中增加的细胞内温度与癌症免疫治疗中细胞的生存获益和耐药性有关。这项工作不仅为微观温度监测提供了一种可靠的方法，也为阐明免疫逃逸和治疗耐药的机制提供了新的见解。
