Nanoparticles target intimal macrophages in atherosclerotic lesions

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. Illustration of structure and composition of ligand-coated nanoparticle (L-NP). The ligand is 1-palmitoyl-2-(4-keto-dodec-3-enedioyl) phosphatidylcholine. L-NP target atherosclerotic lesions through binding to the CD36 receptor of intimal macrophages in LDL receptor null mice. Arrows denote aortas; black arrowheads denote hearts; and red arrowheads denote lesions. [Display omitted]