| The physiological microenvironment of cells is characterised by parameters such as polarity,viscosity,p H,oxygen and temperature,which together determine its physical and chemical properties.As two important parameters in the microenvironment,viscosity/polarity play a vital role in maintaining the environmental homeostasis of organisms,such as cellular characterisation and functional regulation,and abnormal changes in viscosity/polarity can cause a variety of disorders or physiological dysfunctions.Therefore,the detection of changes in polarity/viscosity in cells or organisms is important for revealing the pathological processes of diseases.Fluorescence probe technology has the advantages of high sensitivity,excellent selectivity and operation.Fluorescence imaging is widely used to track changes in subcellular behavior and intracellular signaling factors and monitor of the microenvironment through the change of fluorescence signal,and is suitable for in situ tracking and detecting the changes of temperature,polarity,p H and viscosity in the microenvironment.However,these probes lack specificity and are unable to target polarity and viscosity changes at the level of specific suborganelles.More importantly,such polarity/viscosity detection at the shallow cellular level cannot provide effective support for the early diagnosis of diseases in clinical medicine or related pathologic studies.Therefore,in combination with the current research status of targeting suborganelles,three new polarity/viscosity fluorescence probes have been successfully constructed in this paper,which will help people to deeply understand the changes in the polarity and viscosity of suborganelles during the process of iron death.The details are as follows:Firstly,we designed and synthesized an endoplasmic reticulum targeting fluorescent viscosity probe(PV1)to image the viscosity fluctuations of changes in ER during ferroptosis.PV1 uses a rotatable C-C bond to connect two rigid π-systems and responds to viscosity by modulating the coplanarity of these two planes.PV1 exhibits good sensitivity and selectivity to viscosity.Bioimaging results showed that PV1 was predominantly distributed in the endoplasmic reticulum of living cells and that endoplasmic reticulum viscosity increased significantly during erastin-induced iron death.No significant change in ER viscosity was observed after incubation of cells with erastin,Fer-1 or VE,indicating that erastin-induced ferroptosis could be inhibited by Fer-1 and VE.Thus,the probe PV1 will hopefully provide effective assessment and guidance for biological and pathological studies of ferroptosis-related diseases.Secondly,a Golgi-targeted polarity-responsive near-infrared fluorescent probe(GolgiDCA)was designed to observe changes in Golgi polarity during ferroptosis.The probe exhibited a good solvation response to polarity due to the good donor-π-acceptor(D-π-A)properties of the dicyanomethyl dye in the probe.Bioimaging showed that the probe(GolgiDCA)was predominantly distributed in the Golgi apparatus of living cells and that it provided an increase in specific fluorescence intensity reflecting changes in polarity during erastininduced ferroptosis.After incubation of cells with erastin,Fer-1 or VE or DFO or DHLA simultaneously,the change of Golgi polarity has no obvious change in fluorescence intensity,indicating that erastin-induced ferroptosis could be inhibited by Fer-1 and VE.Thus,the probe(Golgi-DCA)will hopefully provide a feasible and rapid method for in-depth studies and drug design in ferroptosis-related diseases.Thirdly,A polarity-responsive endoplasmic reticulum-targeted fluorescent probe(BNS)was designed to detect changes in ER polarity during.The probe has a D-π-A-π-D dual ICT structure and exhibits high sensitivity to polarity.Bioimaging shows that the probe(BNS)is predominantly distributed in the endoplasmic reticulum of living cells,and during erastininduced ferroptosis,the probe provides an increase in specific fluorescence intensity reflecting changes in polarity.After incubation of cells with erastin,Fer-1,VE or DFO or DHLA simultaneously,there was no significant change in the specific fluorescence intensity of endoplasmic reticulum polarity changes,indicating that erastin-induced ferroptosis could be effectively inhibited by Fer-1,DHLA,DFO and VE.Thus,the probe(BNS)will hopefully become a powerful tool to monitor the process of ferroptosis in biological systems. |
