Abstract
Oxidized phosphatidylcholines (oxPCs) enriched on the oxidized LDL (oxLDL) surface are responsible ligands for binding oxLDL to the CD36 receptor of intimal macrophages in atherosclerotic lesions. We synthesized liposome-like nanoparticles (NPs) using soy phosphatidylcholine and incorporated 1-palmitoyl-2-(4-keto-dodec-3-enedioyl) phosphatidylcholine, a type of oxPCs, on their surface to make ligand-NP (L-NPs). The objectives of this study were to measure and compare their binding affinity to and uptake by primary mouse and THP-1 derived macrophages, and to determine their target specificity to intimal macrophages in aortic lesions in LDL receptor null (LDLr-/-) mice. All in vitro data demonstrate that L-NPs had a high binding affinity to macrophage CD36 receptor. L-NPs had 1.4-fold higher accumulation in aortic lesion areas than NPs. L-NPs co-localized with intimal macrophages and CD36 receptors in the aortic lesions. This target delivery approach may portend a breakthrough in molecular imaging and targeted treatment of atherosclerosis.