Oxidative stress and inflammation are central pathophysiological processes in a traumatic spinal cord injury(SCI).Antioxidant therapies that reduce the reactive oxygen and nitrogen species(RONS)overgeneration and infl...Oxidative stress and inflammation are central pathophysiological processes in a traumatic spinal cord injury(SCI).Antioxidant therapies that reduce the reactive oxygen and nitrogen species(RONS)overgeneration and inflammation are proved promising for improving the outcomes.However,efficient and long-lasting antioxidant therapy to eliminate multiple RONS with effective neuroprotection remains challenging.Here,a single-atom cobalt nanozyme(Co-SAzyme)with a hollow structure was reported to reduce the RONS and inflammation in the secondary injury of SCI.Among SAzymes featuring different single metal-N sites(e.g.,Mn,Fe,Co,Ni,and Cu),this Co-SAzyme showed a versatile property to eliminate hydrogen peroxide(H_(2)O_(2)),superoxide anion(O_(2)·^(-)),hydroxyl radical(·OH),nitric oxide(·NO),and peroxynitrite(ONOO^(-))that overexpressed in the early stage of SCI.The porous hollow structure also allowed the encapsulation and sustained release of minocycline for neuroprotection in synergy.In vitro results showed that the Co-SAzyme reduced the apoptosis and pro-inflammatory cytokine levels of microglial cells under oxidative stress.In addition,the Co-SAzyme combined with minocycline achieved remarkable improved functional recovery and neural repairs in the SCI-rat model.展开更多
Atherosclerosis is an inflammatory disease that may cause severe heart disease and stroke.Current pharmacotherapy for atherosclerosis shows limited benefits.In the progression of atherosclerosis,monocyte adhesions and...Atherosclerosis is an inflammatory disease that may cause severe heart disease and stroke.Current pharmacotherapy for atherosclerosis shows limited benefits.In the progression of atherosclerosis,monocyte adhesions and inflammatory macrophages play vital roles.However,precise regulations of inflammatory immune microenvironments in pathological tissues remain challenging.Here,we report an atherosclerotic plaque-targeted selenopeptide nanomedicine for inhibiting atherosclerosis progression by reducing monocyte adhesions and inflammation of macrophages.The targeted nanomedicine has 2.2-fold enhancement in atherosclerotic lesion accumulation.The oxidation-responsibility of selenopeptide enables eliminations of reactive oxygen species and specific release of anti-inflammatory drugs,thereby reducing inflammation responses of macrophages.Notably,we find the oxidative metabolite of selenopeptide,octadecyl selenite,can bind to P-selectin in a high affinity with a dissociation constant of 1.5μM.This in situ generated active seleno-species further inhibit monocyte adhesions for anti-inflammation in synergy.With local regulations of monocyte adhesions and inflammations,the selenopeptide nanomedicine achieves 2.6-fold improvement in atherosclerotic plaque inhibition compared with simvastatin in the atherosclerosis mouse model.Meanwhile,the selenopeptide nanomedicine also displays excellent biological safety in both mice and rhesus monkeys.This study provides a safe and effective platform for regulating inflammatory immune microenvironments for inflammatory diseases such as atherosclerosis.展开更多
基金This research was financially supported by the National Natural Science Foundation of China(Nos.22175048,22005027,and 51890892)Tianjin Health Commission(No.ZC20175).
文摘Oxidative stress and inflammation are central pathophysiological processes in a traumatic spinal cord injury(SCI).Antioxidant therapies that reduce the reactive oxygen and nitrogen species(RONS)overgeneration and inflammation are proved promising for improving the outcomes.However,efficient and long-lasting antioxidant therapy to eliminate multiple RONS with effective neuroprotection remains challenging.Here,a single-atom cobalt nanozyme(Co-SAzyme)with a hollow structure was reported to reduce the RONS and inflammation in the secondary injury of SCI.Among SAzymes featuring different single metal-N sites(e.g.,Mn,Fe,Co,Ni,and Cu),this Co-SAzyme showed a versatile property to eliminate hydrogen peroxide(H_(2)O_(2)),superoxide anion(O_(2)·^(-)),hydroxyl radical(·OH),nitric oxide(·NO),and peroxynitrite(ONOO^(-))that overexpressed in the early stage of SCI.The porous hollow structure also allowed the encapsulation and sustained release of minocycline for neuroprotection in synergy.In vitro results showed that the Co-SAzyme reduced the apoptosis and pro-inflammatory cytokine levels of microglial cells under oxidative stress.In addition,the Co-SAzyme combined with minocycline achieved remarkable improved functional recovery and neural repairs in the SCI-rat model.
基金financially supported by the National Natural Science Foundation of China(Nos.51890892,22175048,22007024,and 21805058)National Key R&D Program of China(No.2018YFE0205400)Beijing Natural Science Foundation(No.2232072).
文摘Atherosclerosis is an inflammatory disease that may cause severe heart disease and stroke.Current pharmacotherapy for atherosclerosis shows limited benefits.In the progression of atherosclerosis,monocyte adhesions and inflammatory macrophages play vital roles.However,precise regulations of inflammatory immune microenvironments in pathological tissues remain challenging.Here,we report an atherosclerotic plaque-targeted selenopeptide nanomedicine for inhibiting atherosclerosis progression by reducing monocyte adhesions and inflammation of macrophages.The targeted nanomedicine has 2.2-fold enhancement in atherosclerotic lesion accumulation.The oxidation-responsibility of selenopeptide enables eliminations of reactive oxygen species and specific release of anti-inflammatory drugs,thereby reducing inflammation responses of macrophages.Notably,we find the oxidative metabolite of selenopeptide,octadecyl selenite,can bind to P-selectin in a high affinity with a dissociation constant of 1.5μM.This in situ generated active seleno-species further inhibit monocyte adhesions for anti-inflammation in synergy.With local regulations of monocyte adhesions and inflammations,the selenopeptide nanomedicine achieves 2.6-fold improvement in atherosclerotic plaque inhibition compared with simvastatin in the atherosclerosis mouse model.Meanwhile,the selenopeptide nanomedicine also displays excellent biological safety in both mice and rhesus monkeys.This study provides a safe and effective platform for regulating inflammatory immune microenvironments for inflammatory diseases such as atherosclerosis.