Myocardial ischemia-reperfusion (MI/R) injury is common in patients who undergo revascularization therapy for myocardial infarction, often leading to cardiac dysfunction. Carbon monoxide (CO) has emerged as a therapeu...Myocardial ischemia-reperfusion (MI/R) injury is common in patients who undergo revascularization therapy for myocardial infarction, often leading to cardiac dysfunction. Carbon monoxide (CO) has emerged as a therapeutic molecule due to its beneficial properties such as anti-inflammatory, anti-apoptotic, and mitochondrial biogenesis-promoting properties. However, its clinical application is limited due to uncontrolled release, potential toxicity, and poor targeting efficiency. To address these limitations, a peroxynitrite (ONOO )-triggered CO donor (PCOD585) is utilized to generate a poly (lactic-co-glycolic acid) (PLGA)-based, biomimetic CO nanogenerator (M/PCOD@PLGA) that is coated with the macrophage membrane, which could target to the ischemic area and neutralize proinflammatory cytokines. In the ischemic area, local produced ONOO triggers the continuous release of CO from M/PCOD@PLGA, which efficiently ameliorates MI/R injury by clearing harmful ONOO , attenuating the inflammatory response, inhibiting cardiomyocyte apoptosis, and promoting mitochondrial biogenesis. This study provides a novel insight into the safe therapeutic use of CO for MI/R injury by utilizing a novel CO donor combined with biomimetic technology. The M/PCOD@PLGA nanogenerator offers targeted delivery of CO to the ischemic area, minimizing potential toxicity and enhancing therapeutic efficacy.展开更多
Fluorescence-guided surgery calls for development of near-infrared fluorophores.Despite the wide-spread application and a safe clinical record of Indocyanine Green(ICG),its maximal absorption wavelength at780 nm is ra...Fluorescence-guided surgery calls for development of near-infrared fluorophores.Despite the wide-spread application and a safe clinical record of Indocyanine Green(ICG),its maximal absorption wavelength at780 nm is rather short and longer-wavelength dyes are desired to exploit such benefits as low phototoxicity and deep penetration depth.Here,we report ECY,a stable deep near-infrared(NIR)fluorochromic scaffold absorbing/emitting at 836/871 nm with a fluorescence quantum yield of 16%in CH_(2)Cl_(2).ECY was further rationally engineered for biological distribution specificity.Analogous bearing different numbers of sulfonate group or a polyethylene glycol chain were synthesized.By screening this focused library upon intravenous injection to BALB/c mice,ECYS2 was identified to be a suitable candidate for bioimaging of organs involved in hepatobiliary excretion,and ECYPEG was found to be a superior candidate for vasculature imaging.They have potentials in intraoperative imaging.展开更多
基金support by the National Natural Science Foundation of China(81900353,82270264,T2288101,82130010,21908065,22078098,22278138)the National Science Fund for Distinguished Young Scholars(817200010)+1 种基金the Basic research projects of Shanghai Science and Technology Commission(22JC1400500)the Innovation Program of Shanghai Municipal Education Commission.
文摘Myocardial ischemia-reperfusion (MI/R) injury is common in patients who undergo revascularization therapy for myocardial infarction, often leading to cardiac dysfunction. Carbon monoxide (CO) has emerged as a therapeutic molecule due to its beneficial properties such as anti-inflammatory, anti-apoptotic, and mitochondrial biogenesis-promoting properties. However, its clinical application is limited due to uncontrolled release, potential toxicity, and poor targeting efficiency. To address these limitations, a peroxynitrite (ONOO )-triggered CO donor (PCOD585) is utilized to generate a poly (lactic-co-glycolic acid) (PLGA)-based, biomimetic CO nanogenerator (M/PCOD@PLGA) that is coated with the macrophage membrane, which could target to the ischemic area and neutralize proinflammatory cytokines. In the ischemic area, local produced ONOO triggers the continuous release of CO from M/PCOD@PLGA, which efficiently ameliorates MI/R injury by clearing harmful ONOO , attenuating the inflammatory response, inhibiting cardiomyocyte apoptosis, and promoting mitochondrial biogenesis. This study provides a novel insight into the safe therapeutic use of CO for MI/R injury by utilizing a novel CO donor combined with biomimetic technology. The M/PCOD@PLGA nanogenerator offers targeted delivery of CO to the ischemic area, minimizing potential toxicity and enhancing therapeutic efficacy.
基金supported by the National Natural Science Foundation of China(Nos.21908065,22078098,and 22278138)the Shanghai Academic Technology Research Leader(No.22XD1421000)+1 种基金the Research Funds of Happiness Flower ECNU(No.2020JK2103)the Open Funding Project of the State Key Laboratory of Bioreactor Engineering。
文摘Fluorescence-guided surgery calls for development of near-infrared fluorophores.Despite the wide-spread application and a safe clinical record of Indocyanine Green(ICG),its maximal absorption wavelength at780 nm is rather short and longer-wavelength dyes are desired to exploit such benefits as low phototoxicity and deep penetration depth.Here,we report ECY,a stable deep near-infrared(NIR)fluorochromic scaffold absorbing/emitting at 836/871 nm with a fluorescence quantum yield of 16%in CH_(2)Cl_(2).ECY was further rationally engineered for biological distribution specificity.Analogous bearing different numbers of sulfonate group or a polyethylene glycol chain were synthesized.By screening this focused library upon intravenous injection to BALB/c mice,ECYS2 was identified to be a suitable candidate for bioimaging of organs involved in hepatobiliary excretion,and ECYPEG was found to be a superior candidate for vasculature imaging.They have potentials in intraoperative imaging.
