College of Biological, Chemical Sciences and Engineering, Jiaxing University, Jiaxing 314001, China.
School of Life Sciences, Huzhou University, Huzhou, 313000, China.
J Colloid Interface Sci. 2022 Dec;627:705-715. doi: 10.1016/j.jcis.2022.07.095. Epub 2022 Jul 19.
Endoplasmic reticulum (ER) is the largest organelle in eukaryotic cells and plays a variety of functions in living cells include protein folding, calcium homeostasis, and lipid biosynthesis. Normal function of ER is crucial for cell survival, while disequilibrium of ER can cause misfolding of proteins and ER stress, leading to many serious diseases. It has been documented that ER stress is closely related to the metabolism of Cu, as ER is the main intracellular accumulation space of Cu and toxic reactive oxygen species can be generated by Cu via Fenton and Haber-Weiss reactions. In this context, developing a powerful tool capable of selective and sensitive monitoring of Cu in ER and investigating its role in physiological and pathological processes is of great importance. Herein, we report the first ER targeted near infrared (NIR) nanosensor, polymer dots encapsulated with NIR hydrophobic carbon nanodots, for detecting Cu in biosystems. This nanosensor with stable fluorescence showed a fast response toward Cu (120 s) and can be used for the quantification of Cu in a linear range covering from 0.25 to 9.0 μM with a detection limit of 13 nM. In addition, the fluorescence variations of the nanosensor are remarkably specific to Cu in comparison with the other metal ions and amino acids. Moreover, the developed nanosensor exhibited low cytotoxicity, good biocompatibility, and ER targeting ability. Because of these excellent spectroscopic features, the nanosensor was successfully utilized for visualizing Cu fluctuations at the living cell, zebrafish and mouse levels, which further proved its potential application in biological systems.
内质网（ER）是真核细胞中最大的细胞器，在活细胞中发挥多种功能，包括蛋白质折叠、钙稳态和脂质生物合成。ER 的正常功能对细胞存活至关重要，而 ER 的失衡会导致蛋白质错误折叠和 ER 应激，从而导致许多严重的疾病。有文献记载，ER 应激与 Cu 的代谢密切相关，因为 ER 是 Cu 的主要细胞内蓄积空间，Cu 可以通过 Fenton 和 Haber-Weiss 反应产生有毒的活性氧。在这种情况下，开发一种能够选择性和灵敏地监测 ER 中 Cu 并研究其在生理和病理过程中的作用的强大工具非常重要。在此，我们报告了第一个用于检测生物体系中 Cu 的内质网靶向近红外（NIR）纳米传感器，该传感器由包裹 NIR 疏水性碳纳米点的聚合物点组成。这种具有稳定荧光的纳米传感器对 Cu 具有快速响应（120s），可以用于线性范围为 0.25 至 9.0 μM 的 Cu 定量，检测限为 13 nM。此外，与其他金属离子和氨基酸相比，该纳米传感器的荧光变化对 Cu 的特异性非常显著。此外，所开发的纳米传感器具有低细胞毒性、良好的生物相容性和内质网靶向能力。由于这些出色的光谱特性，该纳米传感器成功地用于可视化活细胞、斑马鱼和小鼠水平的 Cu 波动，进一步证明了其在生物系统中的潜在应用。
