Platelet Biomimetic Nanosystem with In Vitro Dual-Modal Imaging Potential for the Detection and Intervention of Early Atherosclerotic Plaques

Atherosclerosis (AS), a prevalent chronic inflammatory disease of medium and large arteries, poses a severe global burden due to its association with life-threatening cardiovascular events, while early detection of vulnerable plaques and targeted intervention remain clinical challenges. To address this, we developed a platelet biomimetic nanosystem (PM@CeOx-P) integrating in vitro dual-modal imaging potential and targeted therapy: cerium oxide nanozymes (CeOx) conjugated with matrix metalloproteinase-2 (MMP-2)-responsive FITC probes (P-FITC) were encapsulated within platelet membranes (PM), leveraging CeOx’s antioxidant/anti-inflammatory activities, PM’s active targeting to damaged vasculature, and the probe-CeOx combination for fluorescence/CT dual-modal imaging. In vitro experiments demonstrated efficient internalization of PM@CeOx-P by RAW264.7 macrophages and foam cells (with higher affinity for foam cells), concentration-dependent inhibition of foam cell formation, significant scavenging of LPS/IFN-γ-induced reactive oxygen species (ROS), and downregulation of pro-inflammatory cytokines (TNF-α, IL-1β), chemokine (MCP-1), and oxidative damage marker (8-OHDG); imaging assays showed stronger CT signals than lohexol and sustained MMP-2-responsive fluorescence recovery (0.5- 10 h). In vivo studies in ApoE⁻/⁻ mice confirmed that PM@CeOx-P specifically accumulates at atherosclerotic lesions within 12 h post-injection, significantly reduces plaque area and macrophage infiltration after 15 days of treatment, and exhibits excellent biosafety (no hemolysis, abnormal blood indices, or organ damage in C57BL/6 mice). Collectively, PM@CeOx-P offers a promising strategy for the early diagnosis and precise treatment of atherosclerosis, with potential clinical translation.