NGPPEVs significantly reduced atherosclerotic plaque area and improved plaque stability with superior therapeutic efficacy compared to free niraparib in ApoE-deficient mice fed a high-fat high-cholesterol diet.
Does targeted delivery of niraparib using platelet-rich plasma-derived extracellular vesicles (NGPPEVs) reduce atherosclerotic plaque area in ApoE-/- mice?
A biomimetic nanoplatform delivering the PARP inhibitor niraparib via platelet-derived extracellular vesicles successfully reduced atherosclerotic plaque burden and inflammation in a preclinical mouse model.
Abstract Macrophage-driven oxidative stress and chronic inflammation play pivotal roles in the progression of atherosclerosis. Given the overactivation of poly (ADP-ribose) polymerase (PARP) in atherosclerosis, PARP inhibitors have potential therapeutic potential, but their efficacy is limited due to poor in vivo targeting. Platelet-rich plasma-derived extracellular vesicles (PEVs), which inherently target inflammatory sites and mitigate oxidative stress, offer a promising delivery platform. Here, we developed NGPPEVs, a nanoplatform that employs PEVs to deliver niraparib, a PARP inhibitor, followed by encapsulation of Ca(HCO₃)₂ to generate gas within cells, thereby combining targeted therapy with ultrasound imaging capabilities. In vitro, NGPPEVs significantly scavenged intracellular reactive oxygen species (ROS) and suppressed pathways related to oxidative stress and cholesterol metabolism. Mechanistically, NGPPEVs suppressed foam cell formation by inhibiting the PARP1–IL-6–CD36 axis, leading to significant downregulation of the key scavenger receptor CD36. In apolipoprotein E-deficient mice fed a high-fat high-cholesterol diet, NGPPEVs demonstrated superior therapeutic efficacy, effectively reducing atherosclerotic plaque area and enhancing plaque stability. Collectively, NGPPEVs have great potential in the precise diagnosis and treatment of atherosclerosis. Graphical Abstract
Fang et al. (Fri,) conducted a other in Apolipoprotein E-deficient mice (6 weeks old, male) fed a high-fat high-cholesterol diet for 12 weeks to model atherosclerosis. NGPPEVs (nanoplatform using platelet-rich plasma-derived extracellular vesicles delivering niraparib co-loaded with Ca(HCO3)2) vs. Free niraparib and GPPEVs without niraparib was evaluated on Atherosclerotic plaque area and plaque stability in aortic tissue of ApoE-/- mice. NGPPEVs significantly reduced atherosclerotic plaque area and improved plaque stability with superior therapeutic efficacy compared to free niraparib in ApoE-deficient mice fed a high-fat high-cholesterol diet.