Glutathione(GSH)-activated prodrugs are promising for overcoming the limitations of conventional anti-tumor drugs.However,current GSH-responsive disulfide groups exhibit unregulated reactivity,making it impossible to ...Glutathione(GSH)-activated prodrugs are promising for overcoming the limitations of conventional anti-tumor drugs.However,current GSH-responsive disulfide groups exhibit unregulated reactivity,making it impossible to precisely control the drug release rate.We herein report a series of GSH-responsive prodrugs with a“three-in-one”molecular design by integrating a fluorescence report unit,stimuliresponsive unit and chemodrug into one scaffold with tunable aromatic nucleophilic substitution(SNAr)reactivity.The drug release rate of these prodrugs is tailored by modification of substituent groups with different electron-withdrawing or-donating abilities on the BODIPY core.Furthermore,the prodrugs self-assemble in water to form nanoparticles that serve as photosensitizers to produce reactive oxygen species upon irradiation for photodynamic therapy(PDT).The PDT process also increases the concentration of GSH in cells,further promoting the release of drugs for chemotherapy.This strategy provides a powerful platform for sequential photodynamic and chemotherapy with tunable drug release rates and synergistic therapeutic effects.展开更多
Evaluating the correlation between hypoxia inducible factor 1(HIF-1) and nitric oxide(NO) generated under hypoxia is of great significance. In this work, we developed a fluorescent probe for the monitor of HIF-1 activ...Evaluating the correlation between hypoxia inducible factor 1(HIF-1) and nitric oxide(NO) generated under hypoxia is of great significance. In this work, we developed a fluorescent probe for the monitor of HIF-1 activity influenced by NO under hypoxia in hepatoma cells with dual-targeting for hepatocyte and lipid droplet(LD). The probe shows excellent selectivity to NO and high sensitivity with 6000-fold fluorescence enhancement. Live cell imaging experiments revealed the probe’s capability of imaging exogenous and endogenous NO with specific in LDs of Hep G2 cells. For cells under hypoxia, HIF-1 induced LD level is observed to correlate with NO level. This work provides the in-situ visualization of NO-dependent HIF-1 upregulation through LD accumulation.展开更多
基金support from the National Natural Science Foundation of China(22177014,22231001 and 21971023)the Fundamental Research Funds for the Central Universities and Key Laboratory of Photochemical Conversion and Optoelectronic Materials,TIPC,CAS.
文摘Glutathione(GSH)-activated prodrugs are promising for overcoming the limitations of conventional anti-tumor drugs.However,current GSH-responsive disulfide groups exhibit unregulated reactivity,making it impossible to precisely control the drug release rate.We herein report a series of GSH-responsive prodrugs with a“three-in-one”molecular design by integrating a fluorescence report unit,stimuliresponsive unit and chemodrug into one scaffold with tunable aromatic nucleophilic substitution(SNAr)reactivity.The drug release rate of these prodrugs is tailored by modification of substituent groups with different electron-withdrawing or-donating abilities on the BODIPY core.Furthermore,the prodrugs self-assemble in water to form nanoparticles that serve as photosensitizers to produce reactive oxygen species upon irradiation for photodynamic therapy(PDT).The PDT process also increases the concentration of GSH in cells,further promoting the release of drugs for chemotherapy.This strategy provides a powerful platform for sequential photodynamic and chemotherapy with tunable drug release rates and synergistic therapeutic effects.
基金financially supported by National Natural Science Foundation of China (Nos. 21971023, 22074007 and 21525206)。
文摘Evaluating the correlation between hypoxia inducible factor 1(HIF-1) and nitric oxide(NO) generated under hypoxia is of great significance. In this work, we developed a fluorescent probe for the monitor of HIF-1 activity influenced by NO under hypoxia in hepatoma cells with dual-targeting for hepatocyte and lipid droplet(LD). The probe shows excellent selectivity to NO and high sensitivity with 6000-fold fluorescence enhancement. Live cell imaging experiments revealed the probe’s capability of imaging exogenous and endogenous NO with specific in LDs of Hep G2 cells. For cells under hypoxia, HIF-1 induced LD level is observed to correlate with NO level. This work provides the in-situ visualization of NO-dependent HIF-1 upregulation through LD accumulation.
