Platelet-rich plasma-derived extracellular vesicles delivered niraparib for ultrasound imaging and atherosclerosis treatment

TL;DR

A new nanoplatform using platelet-derived vesicles delivers a drug to treat atherosclerosis while enabling ultrasound imaging.

Contribution

Developed a targeted delivery system combining PARP inhibition and ultrasound imaging for atherosclerosis treatment.

Findings

NGPPEVs reduced oxidative stress and cholesterol metabolism pathways in vitro.

NGPPEVs inhibited foam cell formation by suppressing the PARP1–IL-6–CD36 axis.

NGPPEVs reduced plaque area and improved stability in a mouse model of atherosclerosis.

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.

The online version contains supplementary material available at 10.1186/s12951-026-04076-z.

Figures