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<p>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.</p> Graphical Abstract <p></p>

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

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年2月6日

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  • Weimin Fang,
  • Wei Zeng,
  • Yalan Huang,
  • Anqi Chen,
  • Yanbin Guo,
  • Guanxi Wen,
  • Jiayu Ye,
  • Jinfeng Xu,
  • Yingying Liu

摘要

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