Lipid nanoparticles encapsulating curcumin for imaging and stabilization of vulnerable atherosclerotic plaques via phagocytic "eat-me" signals.

Curcumin potentiates the stabilization of atherosclerotic plaques by polarizing macrophages, but its non-specific targeting hinders its clinical application. We aim to harness multifunctional lipid nanoparticles (MLNPs) to facilitate the imaging and targeted delivery of curcumin specifically to inflammatory macrophages, counteracting vulnerable plaques and mitigating the risk of ischemic events. Cholesteryl-9-carboxynonanoate-(I‑iron oxide nanoparticle/Curcumin)-lipid-coated nanoparticles [9-CCN-(I-ION/Cur)-LNPs], namely MLNPs, are designed to carry hybrid imaging agents. These agents combine I-ION with lipids containing phagocytic 'eat-me' signals, inducing macrophages to engulf the MLNPs. Our research demonstrates that the designed MLNPs accurately accumulate at unstable plaques and are precisely visualized and highlighted by both SPECT and MRI. Furthermore, MLNPs achieve high efficiency in delivering I-ION and curcumin to macrophages, ultimately leading to significant M1-to-M2 macrophage polarization. These real-time imaging and polarization capabilities of plaques have immediate clinical applicability and may pave the way for novel therapies to stabilize unstable atherosclerotic plaques.