Neutrophil membrane-camouflaged nanoparticles alleviate inflammation and promote angiogenesis in ischemic myocardial injury

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.

Light-triggered NO-releasing nanoparticles for treating mice with liver fibrosis

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.