Acute myocardial infarction(AMI)induces a sterile inflammatory response,leading to cardiomyocyte damage and adverse cardiac remodeling.Interleukin-5(IL-5)plays an essential role in developing eosinophils(EOS),which ar...Acute myocardial infarction(AMI)induces a sterile inflammatory response,leading to cardiomyocyte damage and adverse cardiac remodeling.Interleukin-5(IL-5)plays an essential role in developing eosinophils(EOS),which are beneficial for the resolution of inflammation.Furthermore,the proangiogenic properties of IL-5 also contribute to tissue healing following injury.Therefore,targeted delivery of IL-5 is an innovative therapeutic approach for treating AMI.It has been shown that conventional IL-5 delivery can result in undesirable adverse effects and potential drug overdose.In this study,we successfully synthesized a biomimetic IL-5 nanoparticle by camouflaging the IL-5 nanoparticle in a neutrophilic membrane.The administration of neutrophil membrane-camouflaged nanoparticles(NM-NPIL-5)in the in vivo model showed that these nanoparticles promoted EOS accumulation and angiogenesis in the infarcted myocardium,thereby limiting adverse cardiac remodeling after AMI.Our results also demonstrated that the NM-NPIL-5 could serve as neutrophil“decoys”to adsorb and neutralize the elevated neutrophil-related cytokines in the injured heart by inheriting multiple receptors from their“parent”neutrophils.Finally,the targeted delivery of NM-NPIL-5 protected the cardiomyocytes from excessive inflammatory-induced apoptosis and maintained cardiac function.Our findings provided a promising cardiac detoxification agent for acute cardiac injury.展开更多
Liver fibrosis, resulting from chronic liver damage and characterized by the accumulation of extracellular matrix (ECM) proteins, is a characteristic of most types of chronic liver diseases. The activation of hepatic ...Liver fibrosis, resulting from chronic liver damage and characterized by the accumulation of extracellular matrix (ECM) proteins, is a characteristic of most types of chronic liver diseases. The activation of hepatic stellate cells (HSC) is considered an essential pathological hallmark in liver fibrosis. Although nitric oxide (NO) can effectively induce HSC apoptosis, the systemic administration of NO is ineffective and may cause severe complications such as hypotension. To overcome this limitation, nanoparticles were designed to target HSCs and release NO locally under the exposure of near infrared light (NIR). To achieve this, upconversion nanoparticle (UCNP) cores were enveloped in mesoporous silica shells (UCNP@mSiO2), which were modified with hyaluronic acid (HA-UCNP@mSiO2) and Roussin’s black salt (RBS). HA molecules recognize and bind to CD44 proteins, which are overexpressed on activated HSCs. Under exposure to a 980-nm NIR laser, the UCNP cores convert the 980-nm wavelength into ultraviolet (UV) light, which then energizes the RBS (NO donors), resulting in an efficient release of NO inside of the HSCs. Once released, NO triggers HSC apoptosis and reverses the liver fibrosis. This targeted and controlled release method provides the theoretical and experimental basis for novel therapeutic approaches to treat hepatic fibrosis.展开更多
基金This work was financially supported by the National Science Foundation of China(Grant Nos.81873493 and 82170271 to DL.S.)Henan Thousand Talents Program(Grant Nos.204200510017to DL.S.).Thanks for the help of the research and innovation team project of the First Affiliated Hospital of Zhengzhou University。
文摘Acute myocardial infarction(AMI)induces a sterile inflammatory response,leading to cardiomyocyte damage and adverse cardiac remodeling.Interleukin-5(IL-5)plays an essential role in developing eosinophils(EOS),which are beneficial for the resolution of inflammation.Furthermore,the proangiogenic properties of IL-5 also contribute to tissue healing following injury.Therefore,targeted delivery of IL-5 is an innovative therapeutic approach for treating AMI.It has been shown that conventional IL-5 delivery can result in undesirable adverse effects and potential drug overdose.In this study,we successfully synthesized a biomimetic IL-5 nanoparticle by camouflaging the IL-5 nanoparticle in a neutrophilic membrane.The administration of neutrophil membrane-camouflaged nanoparticles(NM-NPIL-5)in the in vivo model showed that these nanoparticles promoted EOS accumulation and angiogenesis in the infarcted myocardium,thereby limiting adverse cardiac remodeling after AMI.Our results also demonstrated that the NM-NPIL-5 could serve as neutrophil“decoys”to adsorb and neutralize the elevated neutrophil-related cytokines in the injured heart by inheriting multiple receptors from their“parent”neutrophils.Finally,the targeted delivery of NM-NPIL-5 protected the cardiomyocytes from excessive inflammatory-induced apoptosis and maintained cardiac function.Our findings provided a promising cardiac detoxification agent for acute cardiac injury.
基金This work was supported by the American Heart Association(Nos.18TPA34230092 and 19EIA34660286 to K.C.)the National Natural Science Foundation of China(No.U1904149 to H.X.L.)+1 种基金National S&T Major Project of China(No.2018ZX10301201-008 to Z.G.R.)the High Technology Research and Development Program of Henan Province(No.20A320055 to H.X.L.).
文摘Liver fibrosis, resulting from chronic liver damage and characterized by the accumulation of extracellular matrix (ECM) proteins, is a characteristic of most types of chronic liver diseases. The activation of hepatic stellate cells (HSC) is considered an essential pathological hallmark in liver fibrosis. Although nitric oxide (NO) can effectively induce HSC apoptosis, the systemic administration of NO is ineffective and may cause severe complications such as hypotension. To overcome this limitation, nanoparticles were designed to target HSCs and release NO locally under the exposure of near infrared light (NIR). To achieve this, upconversion nanoparticle (UCNP) cores were enveloped in mesoporous silica shells (UCNP@mSiO2), which were modified with hyaluronic acid (HA-UCNP@mSiO2) and Roussin’s black salt (RBS). HA molecules recognize and bind to CD44 proteins, which are overexpressed on activated HSCs. Under exposure to a 980-nm NIR laser, the UCNP cores convert the 980-nm wavelength into ultraviolet (UV) light, which then energizes the RBS (NO donors), resulting in an efficient release of NO inside of the HSCs. Once released, NO triggers HSC apoptosis and reverses the liver fibrosis. This targeted and controlled release method provides the theoretical and experimental basis for novel therapeutic approaches to treat hepatic fibrosis.