Macrophage membrane functionalized biomimetic nanoparticles for targeted anti-atherosclerosis applications.

Atherosclerosis (AS), the underlying cause of most cardiovascular events, is one of the most common causes of human morbidity and mortality worldwide due to the lack of an efficient strategy for targeted therapy. In this work, we aimed to develop an ideal biomimetic nanoparticle for targeted AS therapy. Methods: Based on macrophage "homing" into atherosclerotic lesions and cell membrane coating nanotechnology, biomimetic nanoparticles (MM/RAPNPs) were fabricated with a macrophage membrane (MM) coating on the surface of rapamycin-loaded poly (lactic-co-glycolic acid) copolymer (PLGA) nanoparticles (RAPNPs). Subsequently, the physical properties of the MM/RAPNPs were characterized. The biocompatibility and biological functions of MM/RAPNPs were determined in vitro. Finally, in AS mouse models, the targeting characteristics, therapeutic efficacy and safety of the MM/RAPNPs were examined. Results: The advanced MM/RAPNPs demonstrated good biocompatibility. Due to the MM coating, the nanoparticles effectively inhibited the phagocytosis by macrophages and targeted activated endothelial cells in vitro. In addition, MM-coated nanoparticles effectively targeted and accumulated in atherosclerotic lesions in vivo. After a 4-week treatment program, MM/RAPNPs were shown to significantly delay the progression of AS. Furthermore, MM/RAPNPs displayed favorable safety performance after long-term administration. Conclusion: These results demonstrate that MM/RAPNPs could efficiently and safely inhibit the progression of AS. These biomimetic nanoparticles may be potential drug delivery systems for safe and effective anti-AS applications.

Wang Y ，Zhang K ，Li T ，Maruf A ，Qin X ，Luo L ，Zhong Y ，Qiu J ，McGinty S ，Pontrelli G ，Liao X ，Wu W ，Wang G ... -  《Theranostics》

Targeted delivery of berberine using bionic nanomaterials for Atherosclerosis therapy.

Atherosclerosis (AS) is a prevalent chronic vascular inflammatory disease globally, initiated by injury to vascular endothelial cells (VECs). Macrophages play a pivotal role in disease pathogenesis, involving lipid metabolism and inflammation. The application of nanomaterials has been hindered by their rapid clearance by the immune system. Utilizing macrophage cell membranes can mitigate abnormal immune responses and induce a "homing" effect. Here, M2 macrophage cell membranes (M2) were coated onto berberine polylactic-hydroxylase-polylactide (PLGA) nanoparticles (BBR NPs), employing M2 macrophage immune escape, "homing" ability, and membrane coating nanotechnology, and loaded with mannose (Man) to create bionic nanoparticles (BBR NPs@Man/M2). Subsequently, the physical properties of BBR NPs@Man/M2 were characterized. The biocompatibility and biological function of BBR NPs@Man/M2 were assessed in vitro. Finally, the targeting, therapeutic efficacy, and safety of BBR NPs@M2 were investigated in an AS mouse model. The newly developed BBR NPs@Man/M2 exhibited good biocompatibility. Owing to their M2 coating, the nanoparticles effectively targeted macrophages in vitro, inducing a shift from a pro-inflammatory to an anti-inflammatory state. This transition reduced inflammation in endothelial cells and facilitated the repair of damaged endothelial cells. Moreover, M2-coated nanoparticles efficiently targeted and accumulated in atherosclerotic lesions in vivo. Following four weeks of treatment, BBR NPs@Man/M2 significantly delayed AS progression. Furthermore, BBR NPs@Man/M2 demonstrated a good safety profile after long-term administration. In conclusion, BBR NPs@Man/M2 effectively and safely inhibited AS progression. Biomimetic nanoparticles represent a promising approach for the safe and effective delivery of anti-AS drugs.

Wu H ，Zhang L ，Dong X ，Yang J ，Zheng L ，Li L ，Liu X ，Jin M ，Zhang P ... -  《-》

Biomimetic nanoparticles loaded lutein functionalized by macrophage membrane for targeted amelioration pressure overload-induced cardiac fibrosis.

Guo T ，Chen L ，Li F ，Cao Y ，Li D ，Xiong Q ，Ling Z ... -  《-》

Plaque-hyaluronidase-responsive high-density-lipoprotein-mimetic nanoparticles for multistage intimal-macrophage-targeted drug delivery and enhanced anti-atherosclerotic therapy.

Zhang M ，He J ，Jiang C ，Zhang W ，Yang Y ，Wang Z ，Liu J ... -  《International Journal of Nanomedicine》

Pioglitazone-Incorporated Nanoparticles Prevent Plaque Destabilization and Rupture by Regulating Monocyte/Macrophage Differentiation in ApoE-/- Mice.

Inflammatory monocytes/macrophages produce various proteinases, including matrix metalloproteinases, and degradation of the extracellular matrix by these activated proteinases weakens the mechanical strength of atherosclerotic plaques, which results in a rupture of the plaque. Peroxisome proliferator-activated receptor-γ induces a polarity shift of monocytes/macrophages toward less inflammatory phenotypes and has the potential to prevent atherosclerotic plaque ruptures. Therefore, we hypothesized that nanoparticle-mediated targeted delivery of the peroxisome proliferator-activated receptor-γ agonist pioglitazone into circulating monocytes could effectively inhibit plaque ruptures in a mouse model. We prepared bioabsorbable poly(lactic-co-glycolic-acid) nanoparticles containing pioglitazone (pioglitazone-NPs). Intravenously administered poly(lactic-co-glycolic-acid) nanoparticles incorporated with fluorescein isothiocyanate were found in circulating monocytes and aortic macrophages by flow cytometric analysis. Weekly intravenous administration of pioglitazone-NPs (7 mg/kg per week) for 4 weeks decreased buried fibrous caps, a surrogate marker of plaque rupture, in the brachiocephalic arteries of ApoE(-/-) mice fed a high-fat diet and infused with angiotensin II. In contrast, administration of control-NPs or an equivalent dose of oral pioglitazone treatment produced no effects. Pioglitazone-NPs inhibited the activity of matrix metalloproteinases and cathepsins in the brachiocephalic arteries. Pioglitazone-NPs regulated inflammatory cytokine expression and also suppressed the expression of extracellular matrix metalloproteinase inducer in bone marrow-derived macrophages. Nanoparticle-mediated delivery of pioglitazone inhibited macrophage activation and atherosclerotic plaque ruptures in hyperlipidemic ApoE(-/-) mice. These results demonstrate a promising strategy with a favorable safety profile to prevent atherosclerotic plaque ruptures.

Nakashiro S ，Matoba T ，Umezu R ，Koga J ，Tokutome M ，Katsuki S ，Nakano K ，Sunagawa K ，Egashira K ... -  《-》