Hippocampal sclerosis,characterized by significant hippocampal neuronal loss,oxidative stress,glial cell proliferation,and inflammatory responses,constitutes a pivotal component in the pathogenesis of temporal lobe ep...Hippocampal sclerosis,characterized by significant hippocampal neuronal loss,oxidative stress,glial cell proliferation,and inflammatory responses,constitutes a pivotal component in the pathogenesis of temporal lobe epilepsy(TLE).Traditional treatment strategies,mainly involving anti-epileptic drugs,face challenges including ineffectiveness,drug tolerance,and adverse reactions,complicating management of the condition.Herein,we design and engineer ultrasmall potassium calcium hexacyanoferrate(III)nanoparticles,designated as KCaHNPs,which feature a broad spectrum of enzymatic activities analogous to superoxide dismutase,catalase,peroxidase,and glutathione peroxidase.KCaHNPs efficiently neutralize excessive reactive oxygen species,mitigate mitochondrial dysfunction,maintain neuronal integrity,and prevent apoptosis.Importantly,KCaHNPs significantly reduce neuronal damage,apoptosis,ferroptosis,and glial cells activation in TLE-afflicted rats,thereby improving spatial and short-term memory,and diminishing epileptic hyperexcitability.Prophylactic deployment of KCaHNPs markedly decreases the frequency and duration of seizures,extends the latency period before the onset of initial seizures,and enhances neural functions within the hippocampal CA3 area.Collectively,these findings underscore the potent therapeutic and prophylactic efficacy of KCa HNPs in mitigating TLE by bolstering cellular defense mechanisms against oxidative stress and inflammation.This innovative approach holds promise as a comprehensive and efficacious strategy for managing temporal lobe epilepsy and potentially other complex neurological disorders.展开更多
Hepatic carcinoma(HC)is the sixth most frequently occurring malignancies and the third leading cause of cancer death worldwide.Sepantronium bromide(YM155)is a small molecule inhibitor of survivin,which has broad-spect...Hepatic carcinoma(HC)is the sixth most frequently occurring malignancies and the third leading cause of cancer death worldwide.Sepantronium bromide(YM155)is a small molecule inhibitor of survivin,which has broad-spectrum anticancer therapeutic effects in various xenograft models.However,several-day continuous infusion is required to achieve greater antitumor efficacy because of rapid elimination from the blood circulation.Herein,a SMMC-7721 cancerous cyto-membrane-cloaked drug delivery system(DDS)(named as iM7721@GQD-YM),was developed for co-encapsulation of YM155 and graphene quantum dots(GQDs).Cytomembrane coating endowed iM7721@GQD-YM with effective targeting for homologous HC cells,excellent biocompatibility and favorable immunocompatibility for in vivo application.Surface decoration of iRGD peptide further enhanced its tumor targeting activity by iRGD-integrin recognition.In addition,under the irradiation of near-infrared ray(NIR),GQDs can directly kill tumors through photothermal effect and cause cell membrane rupture,accurately releasing YM155 at tumor sites.The physicochemical properties,in vivo and ex vivo anti-tumor efficacy,and mechanisms of iM7721@GQD-YM nanoparticles(NPs)were systematically investigated in this work.The experimental results clearly indicate that the versatile biomimetic DDS holds great potential for the treatment of HC,which merits further investigation in both pre-clinical and clinical studies.展开更多
基金supported by the National Natural Science Foundation of China(52002239,52272279,and 52072393)International Collaboration Project of Chinese Academy of Sciences(GJHZ2072)+4 种基金Shanghai Shuguang Program(21SG39)Shanghai Science and Technology Committee Rising-Star Program(21QA1403100)Shanghai Science and Technology Committee Biomedical Program(23S11900900)Shanghai Sailing Program(22YF1413000)Wenzhou Basic Scientific Research Project(Y20220138)。
文摘Hippocampal sclerosis,characterized by significant hippocampal neuronal loss,oxidative stress,glial cell proliferation,and inflammatory responses,constitutes a pivotal component in the pathogenesis of temporal lobe epilepsy(TLE).Traditional treatment strategies,mainly involving anti-epileptic drugs,face challenges including ineffectiveness,drug tolerance,and adverse reactions,complicating management of the condition.Herein,we design and engineer ultrasmall potassium calcium hexacyanoferrate(III)nanoparticles,designated as KCaHNPs,which feature a broad spectrum of enzymatic activities analogous to superoxide dismutase,catalase,peroxidase,and glutathione peroxidase.KCaHNPs efficiently neutralize excessive reactive oxygen species,mitigate mitochondrial dysfunction,maintain neuronal integrity,and prevent apoptosis.Importantly,KCaHNPs significantly reduce neuronal damage,apoptosis,ferroptosis,and glial cells activation in TLE-afflicted rats,thereby improving spatial and short-term memory,and diminishing epileptic hyperexcitability.Prophylactic deployment of KCaHNPs markedly decreases the frequency and duration of seizures,extends the latency period before the onset of initial seizures,and enhances neural functions within the hippocampal CA3 area.Collectively,these findings underscore the potent therapeutic and prophylactic efficacy of KCa HNPs in mitigating TLE by bolstering cellular defense mechanisms against oxidative stress and inflammation.This innovative approach holds promise as a comprehensive and efficacious strategy for managing temporal lobe epilepsy and potentially other complex neurological disorders.
基金“One Belt One Road”International Cooperation Project of Shanghai Municipal Committee of Science and Technology(No.19410740900)the National Natural Science Foundation of China(No.52002239)+1 种基金the International Science and Technology Cooperation Programme of Ministry of Science and Technology of China(No.2019YFE0116800)Natural Science Foundation of Shanghai(No.21ZR1422800).
文摘Hepatic carcinoma(HC)is the sixth most frequently occurring malignancies and the third leading cause of cancer death worldwide.Sepantronium bromide(YM155)is a small molecule inhibitor of survivin,which has broad-spectrum anticancer therapeutic effects in various xenograft models.However,several-day continuous infusion is required to achieve greater antitumor efficacy because of rapid elimination from the blood circulation.Herein,a SMMC-7721 cancerous cyto-membrane-cloaked drug delivery system(DDS)(named as iM7721@GQD-YM),was developed for co-encapsulation of YM155 and graphene quantum dots(GQDs).Cytomembrane coating endowed iM7721@GQD-YM with effective targeting for homologous HC cells,excellent biocompatibility and favorable immunocompatibility for in vivo application.Surface decoration of iRGD peptide further enhanced its tumor targeting activity by iRGD-integrin recognition.In addition,under the irradiation of near-infrared ray(NIR),GQDs can directly kill tumors through photothermal effect and cause cell membrane rupture,accurately releasing YM155 at tumor sites.The physicochemical properties,in vivo and ex vivo anti-tumor efficacy,and mechanisms of iM7721@GQD-YM nanoparticles(NPs)were systematically investigated in this work.The experimental results clearly indicate that the versatile biomimetic DDS holds great potential for the treatment of HC,which merits further investigation in both pre-clinical and clinical studies.
