Hyperbranched polysiloxane-based probe with enhanced lipophilicity for visualizing ONOO- fluctuations in endoplasmic reticulum

The endoplasmic reticulum, a cellular signaling regulator, participates in the synthesis and secretion of many proteins, glycogen, lipids and cholesterol substances. Peroxynitrite (ONOO-) is a highly oxidative and nucleo-philic agent. Abnormal fluctuations of ONOO- induce oxidative stress in the endoplasmic reticulum, further disrupting the normal function of protein folding and transport and glycosylation modification, ultimately leading to neurodegenerative diseases, cancer and Alzheimer's disease. Up to now, most probes have tended to achieve targeting functions by introducing specific targeting groups. However, this approach increased the difficulty of the construction process. Therefore, a simple and efficient construction strategy for fluorescent probes with excellent specificity targeting the endoplasmic reticulum is lacking. To overcome this difficulty and put forward an efficient design strategy for the endoplasmic reticulum targeted probes, in this paper, we con-structed alternating rigid and flexible polysiloxane-based hyperbranched polymeric probes (Si-Er-ONOO) by bonding perylenetetracarboxylic anhydride and silicon-based dendrimers for the first time. Efficient and specific targeting of the endoplasmic reticulum was successfully achieved by the excellent lipid solubility of Si-Er-ONOO. Furthermore, we observed different effects of metformin and rotenone on the changes of ONOO- volatility in the cellular and zebrafish internal environment by Si-Er-ONOO. We believe that Si-Er-ONOO will expand the application of organosilicon hyperbranched polymeric materials in bioimaging and provide an excellent indicator of reactive oxygen species fluctuations in biological systems.

Automated summary

The endoplasmic reticulum, a cellular signaling regulator, plays an important role in the synthesis and secretion of various substances. Abnormal fluctuations of peroxynitrite (ONOO-) in the endoplasmic reticulum can lead to oxidative stress and disrupt normal cellular functions, potentially causing neurodegenerative diseases, cancer, and Alzheimer's disease. In this study, researchers developed a fluorescent probe (Si-Er-ONOO) that targets the endoplasmic reticulum, using a construction strategy based on polysiloxane-based hyperbranched polymers. The probe exhibited excellent lipid solubility and allowed for efficient and specific targeting of the endoplasmic reticulum. The researchers also used Si-Er-ONOO to study the effects of certain drugs on ONOO- fluctuations in cellular and zebrafish environments.