In acute ischemic stroke therapy,potent neuroprotective agents are needed that prevent neural injuries caused by reactive oxygen species(ROS)during ischemic reperfusion.Herein,a novel 2D neuroprotective agent(AFGd-LDH...In acute ischemic stroke therapy,potent neuroprotective agents are needed that prevent neural injuries caused by reactive oxygen species(ROS)during ischemic reperfusion.Herein,a novel 2D neuroprotective agent(AFGd-LDH)is reported,comprising Gd-containing layered double hydroxide nanosheets(Gd-LDH,as a drug nanocarrier/MRI contrast agent),atorvastatin(ATO,as a neuroprotective drug)and the ferritin heavy subunit(FTH,as a blood brain barrier transport agent).Experiments revealed AFGd-LDH to possess outstanding antioxidant activity,neuroprotective properties,blood‒brain barrier transit properties,and biocompatibility.In vitro studies demonstrated the ROS scavenging efficiency of AFGd‒LDH to be~90%,surpassing CeO_(2)(50%,a ROS scavenger)and edaravone(52%,a clinical neuroprotective drug).Ischemia‒reperfusion model studies in mice showed AFGd‒LDH could dramatically decrease apoptosis induced by reperfusion,reducing the infarct area by 67%and lowering the neurological deficit score from 3.2 to 0.9.AFGd-LDH also offered outstanding MRI performance,thus enabling simultaneous imaging and ischemia reperfusion therapy.展开更多
In contrast to reactive oxygen species(ROS),the generation of oxygen-irrelevant free radicals is oxygen-and H2O2-independent in cell,which can offer novel opportunities to maximum the chemodynamic therapy(CDT)efficacy...In contrast to reactive oxygen species(ROS),the generation of oxygen-irrelevant free radicals is oxygen-and H2O2-independent in cell,which can offer novel opportunities to maximum the chemodynamic therapy(CDT)efficacy.Herein,an H2O2-independent“functional reversion”strategy based on tumor microenvironment(TME)-toggled C-free radical generation for CDT is developed by confining astaxanthin(ATX)on the NiFe-layered double hydroxide(LDH)nanosheets(denoted as ATX/LDH).The unique ATX/LDH can demonstrate outstanding TME-responsive C-free radical generation performance by proton coupled electron transfer(PCET),owing to the specific ATX activation by unsaturated Fe sites on the LDH nanosheets formed under TME.Significantly,the Brönsted base sites of LDH hydroxide layers can promote the generation of neutral ATX C-free radicals by capturing the protons generated in the ATX activation process.Conversely,ATX/LDH maintain antioxidant performance to prevent normal tissue cancerization due to the synergy of LDH nanosheets and antioxidative ATX.In addition,C-free radical can compromise the antioxidant defense in cells to the maximum extent,compared with ROS.The free radicals burst under TME can significantly elevate free radical stress and induce cancer cell apoptosis.This strategy can realize TME-toggled C free radical generation and perform free radical stress enhanced CDT.展开更多
基金support from National Natural Science Foundation of China(7172070,81771233,21805293,U20A20254,52072253)the Youth Innovation Promotion Association of Chinese Academy of Sciences(No.2019027)+2 种基金the Director Foundation of the Technical Institute of Physics and Chemistry,Chinese Academy of SciencesBeijing Science and Technology Plan subject:Beijing‒Tianjin‒Hebei collaborative innovation promotion project(No.Z181100009618035)National Key Research and Development Program(2018YFC1311602,2018YFC1312801,2016YF1301500).
文摘In acute ischemic stroke therapy,potent neuroprotective agents are needed that prevent neural injuries caused by reactive oxygen species(ROS)during ischemic reperfusion.Herein,a novel 2D neuroprotective agent(AFGd-LDH)is reported,comprising Gd-containing layered double hydroxide nanosheets(Gd-LDH,as a drug nanocarrier/MRI contrast agent),atorvastatin(ATO,as a neuroprotective drug)and the ferritin heavy subunit(FTH,as a blood brain barrier transport agent).Experiments revealed AFGd-LDH to possess outstanding antioxidant activity,neuroprotective properties,blood‒brain barrier transit properties,and biocompatibility.In vitro studies demonstrated the ROS scavenging efficiency of AFGd‒LDH to be~90%,surpassing CeO_(2)(50%,a ROS scavenger)and edaravone(52%,a clinical neuroprotective drug).Ischemia‒reperfusion model studies in mice showed AFGd‒LDH could dramatically decrease apoptosis induced by reperfusion,reducing the infarct area by 67%and lowering the neurological deficit score from 3.2 to 0.9.AFGd-LDH also offered outstanding MRI performance,thus enabling simultaneous imaging and ischemia reperfusion therapy.
基金the financial support from the National Natural Science Foundation of China(No.21571013,52073023,and 21805293)the National Basic Research Program(No.2014CB932101)+2 种基金the Program for Chang Jiang Scholars,Innovative Research Team in University(No.IRT1205)the Youth Innovation Promotion Association of Chinese Academy of Sciences(No.2019027)the Director Foundation of the Technical Institute of Physics and Chemistry,Chinese Academy of Sciences.
文摘In contrast to reactive oxygen species(ROS),the generation of oxygen-irrelevant free radicals is oxygen-and H2O2-independent in cell,which can offer novel opportunities to maximum the chemodynamic therapy(CDT)efficacy.Herein,an H2O2-independent“functional reversion”strategy based on tumor microenvironment(TME)-toggled C-free radical generation for CDT is developed by confining astaxanthin(ATX)on the NiFe-layered double hydroxide(LDH)nanosheets(denoted as ATX/LDH).The unique ATX/LDH can demonstrate outstanding TME-responsive C-free radical generation performance by proton coupled electron transfer(PCET),owing to the specific ATX activation by unsaturated Fe sites on the LDH nanosheets formed under TME.Significantly,the Brönsted base sites of LDH hydroxide layers can promote the generation of neutral ATX C-free radicals by capturing the protons generated in the ATX activation process.Conversely,ATX/LDH maintain antioxidant performance to prevent normal tissue cancerization due to the synergy of LDH nanosheets and antioxidative ATX.In addition,C-free radical can compromise the antioxidant defense in cells to the maximum extent,compared with ROS.The free radicals burst under TME can significantly elevate free radical stress and induce cancer cell apoptosis.This strategy can realize TME-toggled C free radical generation and perform free radical stress enhanced CDT.