Reactive oxygen species(ROS)-mediated oxidative stress exacerbates chronic diseases such as organ damage and neurodegenerative disorders.The Keap1-Nrf2-ARE pathway is a widely distributed endogenous antioxidant system...Reactive oxygen species(ROS)-mediated oxidative stress exacerbates chronic diseases such as organ damage and neurodegenerative disorders.The Keap1-Nrf2-ARE pathway is a widely distributed endogenous antioxidant system.However,ROS under redox homeostasis regulates a wide range of life activities.Therefore,smart scavenging of excess ROS under pathological conditions is essential to treat chronic diseases safely.This study reports a smart antioxidant function enhancement(SAFE)strategy.On-demand release of nucleic acid drugs in a pathological ROS environment smartly activates the endogenous antioxidant system,thereby smartly alleviating oxidative stress in an exogenous antioxidant-independent manner.Through structural modulation and ligand modification,we develop SAFE nanoparticles based on nanohybrid complexes(SAFE-complex)adapted to brain delivery of nucleic acid drugs.SAFE-complex with homogeneous monodisperse structure efficiently treat ROS-related neurodegenerative diseases while protecting the major organ from oxidative stress damage.Moreover,SAFE-complex can stabilize storage in the form of freeze-dried powder.These data indicate that SAFE nanoparticles hold promise for treating ROS-related chronic diseases and comorbidities through rational transformation.展开更多
基金supported by the National Natural Science Foundation of China(Nos.32225029,22205240,52073287,22075289,and 82071552).
文摘Reactive oxygen species(ROS)-mediated oxidative stress exacerbates chronic diseases such as organ damage and neurodegenerative disorders.The Keap1-Nrf2-ARE pathway is a widely distributed endogenous antioxidant system.However,ROS under redox homeostasis regulates a wide range of life activities.Therefore,smart scavenging of excess ROS under pathological conditions is essential to treat chronic diseases safely.This study reports a smart antioxidant function enhancement(SAFE)strategy.On-demand release of nucleic acid drugs in a pathological ROS environment smartly activates the endogenous antioxidant system,thereby smartly alleviating oxidative stress in an exogenous antioxidant-independent manner.Through structural modulation and ligand modification,we develop SAFE nanoparticles based on nanohybrid complexes(SAFE-complex)adapted to brain delivery of nucleic acid drugs.SAFE-complex with homogeneous monodisperse structure efficiently treat ROS-related neurodegenerative diseases while protecting the major organ from oxidative stress damage.Moreover,SAFE-complex can stabilize storage in the form of freeze-dried powder.These data indicate that SAFE nanoparticles hold promise for treating ROS-related chronic diseases and comorbidities through rational transformation.
