Ischemic stroke remains a leading global cause of mortality and long-term disability,with current therapeutic strategies limited to mechanical thrombectomy and intravenous tissue plasminogen activator(tPA)administrati...Ischemic stroke remains a leading global cause of mortality and long-term disability,with current therapeutic strategies limited to mechanical thrombectomy and intravenous tissue plasminogen activator(tPA)administration.Although tPA improves clinical outcomes via timely reperfusion,its clinical utility is limited by life-threatening complications such as cerebral hemorrhage and edema.This review critically examines the limitations of conventional tPA therapy and proposes nanoparticle-based delivery systems as transformative strategies to enhance thrombolytic precision and safety.Engineered nanoparticles address key challenges by(1)stabilizing tPA against rapid degradation,extending its plasma half-life;(2)enabling thrombus-targeted delivery through surface modifications(e.g.,arginine-glycine-aspartic acid(RGD)peptides),thereby reducing systemic bleeding risks;and(3)conferring neuroprotection via reactive oxygen species(ROS)scavenging and inflammation modulation.Emerging platforms—including PEGylated liposomes,gold nanoparticles,platelet-mimetic carriers,and ultrasound-responsive systems—demonstrate enhanced thrombolytic efficacy when combined with tPA.Notably,ultrasound-triggered nanoparticle activation synergistically improves clot penetration while mitigating ischemia-reperfusion injury.Consequently,these multifunctional nanoplatforms represent a paradigm shift in stroke management,offering safer and more effective strategies to optimize thrombolytic therapy.展开更多
Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)is still rapidly spreading worldwide.Many drugs and vaccines have been approved for clinical use show efficacy in the treatment and prevention of SARS-CoV-2 i...Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)is still rapidly spreading worldwide.Many drugs and vaccines have been approved for clinical use show efficacy in the treatment and prevention of SARS-CoV-2 infections.However,the emergence of SARS-CoV-2 variants of concern(VOCs),such as Delta(B.1.617.2)and the recently emerged Omicron(B.1.1.529),has seriously challenged the application of current therapeutics.Therefore,there is still a pressing need for identification of new broad-spectrum antivirals.Here,we further characterized a human antibody(58G6),which we previously isolated from a patient,with a broadly authentic virus-neutralizing activity that inhibits the Delta and Omicron variants with half-maximal inhibitory concentrations(ICso)of 1.69 ng/ml and 54.31 ng/ml,respectively.58G6 shows prophylactic and therapeutic effcacy in hamsters challenged with the Delta and Omicron variants through nasal delivery.Notably,a very low dosage(2 mg/kg daily)of 58G6 efficiently prevented Omicron variant replication in the lungs.These advantages may overcome the efficacy limitation of currently approved neutralizing antibodies that can be administered only by intravenous injection.In general,58G6 is a promising prophylactic and therapeutic candidate against current circulating VOCs and even future emerging mutants.To the best of our knowledge,58G6 is one of the most potent neutralizing antibodies against Omicron,with a broader spectrum than those approved for clinical use.58G6 could be developed as a nebulized therapy,which would be more cost effective and user friendly and enhance the clinical outcome comparedto thatobtainedwithdirect nasaldelivery.展开更多
基金supported by the National Key R&D Program of China(Grant Nos.2022YFA1206500,2021YFB3800900)the National Natural Science Foundation of China(Grant Nos.U22A20161,52073236,52473324,52495011,52033007,32401180)+1 种基金Sichuan Science and Technology Program(Grant No.2024NSFTD0002)the Fundamental Research Funds for the Central Universities(Grant Nos.2682023ZTPY083,2682025CX069)。
文摘Ischemic stroke remains a leading global cause of mortality and long-term disability,with current therapeutic strategies limited to mechanical thrombectomy and intravenous tissue plasminogen activator(tPA)administration.Although tPA improves clinical outcomes via timely reperfusion,its clinical utility is limited by life-threatening complications such as cerebral hemorrhage and edema.This review critically examines the limitations of conventional tPA therapy and proposes nanoparticle-based delivery systems as transformative strategies to enhance thrombolytic precision and safety.Engineered nanoparticles address key challenges by(1)stabilizing tPA against rapid degradation,extending its plasma half-life;(2)enabling thrombus-targeted delivery through surface modifications(e.g.,arginine-glycine-aspartic acid(RGD)peptides),thereby reducing systemic bleeding risks;and(3)conferring neuroprotection via reactive oxygen species(ROS)scavenging and inflammation modulation.Emerging platforms—including PEGylated liposomes,gold nanoparticles,platelet-mimetic carriers,and ultrasound-responsive systems—demonstrate enhanced thrombolytic efficacy when combined with tPA.Notably,ultrasound-triggered nanoparticle activation synergistically improves clot penetration while mitigating ischemia-reperfusion injury.Consequently,these multifunctional nanoplatforms represent a paradigm shift in stroke management,offering safer and more effective strategies to optimize thrombolytic therapy.
基金This work was jointly supported by the Natural Science Foundation of Hubei Province of China(2019CFA076)the National Natural Science Foundation of China(32170949).
文摘Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)is still rapidly spreading worldwide.Many drugs and vaccines have been approved for clinical use show efficacy in the treatment and prevention of SARS-CoV-2 infections.However,the emergence of SARS-CoV-2 variants of concern(VOCs),such as Delta(B.1.617.2)and the recently emerged Omicron(B.1.1.529),has seriously challenged the application of current therapeutics.Therefore,there is still a pressing need for identification of new broad-spectrum antivirals.Here,we further characterized a human antibody(58G6),which we previously isolated from a patient,with a broadly authentic virus-neutralizing activity that inhibits the Delta and Omicron variants with half-maximal inhibitory concentrations(ICso)of 1.69 ng/ml and 54.31 ng/ml,respectively.58G6 shows prophylactic and therapeutic effcacy in hamsters challenged with the Delta and Omicron variants through nasal delivery.Notably,a very low dosage(2 mg/kg daily)of 58G6 efficiently prevented Omicron variant replication in the lungs.These advantages may overcome the efficacy limitation of currently approved neutralizing antibodies that can be administered only by intravenous injection.In general,58G6 is a promising prophylactic and therapeutic candidate against current circulating VOCs and even future emerging mutants.To the best of our knowledge,58G6 is one of the most potent neutralizing antibodies against Omicron,with a broader spectrum than those approved for clinical use.58G6 could be developed as a nebulized therapy,which would be more cost effective and user friendly and enhance the clinical outcome comparedto thatobtainedwithdirect nasaldelivery.
