NaYbF ₄ :Er,Ce@NaYF ₄ Core–Shell Nanoparticles for Ex Vivo NIR-II Fluorescence Molecular Imaging of Atherosclerosis

Atherosclerosis (AS) is a highly prevalent and life-threatening cardiovascular disease that underlies major clinical events such as myocardial infarction and stroke. Yet, precise identification of different pathological stages of AS remains a major challenge for early diagnosis and therapeutic intervention. Here, we report the rational design and synthesis of second near-infrared (NIR-II, 1000–1700 nm) emitting NaYbF4:2%Er,2%Ce@NaYF4 core–shell nanoparticles (NPs) for different stage-specific AS imaging. By varying the precursor feed ratio, NaYF4 inert shells with thicknesses of 5 and 7 nm were epitaxially grown, further increasing photoluminescence (PL) intensity and extending fluorescence lifetimes to 6.8 and 8.8 ms, respectively. The NPs were functionalized with cLABL peptide and osteopontin (OPN) antibody to target intercellular adhesion molecule-1 (ICAM-1) on activated endothelial cells and OPN on foam cells, achieving excellent targeting specificity with a 6-fold increase in cellular uptake for foam cells by using NaYbF4:2%Er@NaYF4@OPN. Ex vivo NIR-II fluorescence imaging of aorta tissues further supported the probe’s high specificity for AS lesions under the tested conditions. This study demonstrates a preliminary NIR-II nanoplatform that shows potential for targeting molecules associated with different stages of AS in vitro and ex vivo, providing an initial basis for future imaging research on the prevention and diagnosis of cardiovascular disease.