Targeted neutrophil-mimetic liposomes promote cardiac repair by adsorbing proinflammatory cytokines and regulating the immune microenvironment

Abstract

Acute myocardial infarction (MI) induces a sterile inflammatory response that may result in poor cardiac remodeling and dysfunction. Despite the progress in anti-cytokine biologics, anti-inflammation therapy of MI remains unsatisfactory, due largely to the lack of targeting and the complexity of cytokine interactions. Based on the nature of inflammatory chemotaxis and the cytokine-binding properties of neutrophils, we fabricated biomimetic nanoparticles for targeted and broad-spectrum anti-inflammation therapy of MI. By fusing neutrophil membranes with conventional liposomes, we fabricated biomimetic liposomes (Neu-LPs) that inherited the surface antigens of the source cells, making them ideal decoys of neutrophil-targeted biological molecules. Based on their abundant chemokine and cytokine membrane receptors, Neu-LPs targeted infarcted hearts, neutralized proinflammatory cytokines, and thus suppressed intense inflammation and regulated the immune microenvironment. Consequently, Neu-LPs showed significant therapeutic efficacy by providing cardiac protection and promoting angiogenesis in a mouse model of myocardial ischemia–reperfusion. Therefore, Neu-LPs have high clinical translation potential and could be developed as an anti-inflammatory agent to remove broad-spectrum inflammatory cytokines during MI and other neutrophil-involved diseases. Graphical Abstract

Beyond Extracellular Vesicles: Hybrid Membrane Nanovesicles as Emerging Advanced Tools for Biomedical Applications

“…For example, Chen et al produced anti‐inflammatory HMNVs by fusing the PEG‐modified liposomes with neutrophil membranes with the nature of inflammatory chemotaxis to target the acute myocardial injury sites and eliminate inflammation. [ 41 ] Besides, Deng et al. fused the Celastrol‐loaded PEGylated liposomes with the DC2.4 cell membranes to greatly enhance Celastrol tumor accumulation and efficiently treat KRAS‐mutated pancreatic cancer both in vitro and in vivo.…”

Immune cells drive new immunomodulatory therapies for myocardial infarction: From basic to clinical translation

“…Similarly, in another study, neutrophil-mimetic liposomes (Neu-LPs) were created by fusing neutrophil membranes with liposomes, which inherit neutrophil surface antigens but without neutrophil activity. Neu-LPs target the infarcted heart, neutralize pro-inflammatory cytokines, thereby suppressing intense inflammation and modulating the immune microenvironment ( 82 ). Furthermore, in a mouse MI model, administration of PF-1355 (MPO inhibitor) for 7 days reduced inflammatory cell infiltration and attenuated left ventricular dilation, and MPO inhibition has been shown to improve ischemia-related cardiac remodeling in animal experiments ( 50 ).…”

An ischemia-homing bioengineered nano-scavenger for specifically alleviating multiple pathogeneses in ischemic stroke

“…Particularly, over-activated M1 phenotype microglia cells play an important role in ischemic stroke injury which can trigger neuroinflammation and neuronal dysfunction [ 23 , 25 – 29 ]. On the other hand, the reperfusion initiates overproduction of reactive oxygen species (ROS) in the ischemic site including hydrogen peroxide (H 2 O 2 ), superoxide anion (·O 2 − ), and hydroxyl radical (·OH), which is another well-known crucial pathological cause of ischemic stroke [ 30 – 33 ]. The upregulated ROS can not only directly induce mitochondrial damage and neuron apoptosis but also serve as important signaling regulators to stimulate the activation of resident microglia and infiltrated peripheral leukocytes via the nuclear factor-κB (NF-κB) signaling pathway, thus ultimately aggravating the inflammation [ 20 , 34 – 39 ].…”

“…), and hydroxyl radical (•OH), which is another well-known crucial pathological cause of ischemic stroke [30][31][32][33]. The upregulated ROS can not only directly induce mitochondrial damage and neuron apoptosis but also serve as important signaling regulators to stimulate the activation of resident microglia and infiltrated peripheral leukocytes via the nuclear factor-κB (NF-κB) signaling pathway, thus ultimately aggravating the inflammation [20,[34][35][36][37][38][39].…”