TY - JOUR
T1 - Nanoparticles target intimal macrophages in atherosclerotic lesions
AU - Dhanasekara, Chathurika S.
AU - Zhang, Jia
AU - Nie, Shufang
AU - Li, Guigen
AU - Fan, Zhaoyang
AU - Wang, Shu
N1 - Funding Information:
Funding: This work was supported by the National Institutes of Health ( 1R15AT007013 and 1R15AT010395 ). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
Publisher Copyright:
© 2020 Elsevier Inc.
PY - 2021/2
Y1 - 2021/2
N2 - 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.
AB - 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.
KW - 1-Palmitoyl-2-(4-keto-dodec-3-enedioyl) phosphatidylcholine
KW - Atherosclerosis
KW - CD36 receptors
KW - Macrophages
KW - Nanoparticles
KW - Targeted delivery
UR - http://www.scopus.com/inward/record.url?scp=85098126024&partnerID=8YFLogxK
U2 - 10.1016/j.nano.2020.102346
DO - 10.1016/j.nano.2020.102346
M3 - Article
C2 - 33259961
AN - SCOPUS:85098126024
VL - 32
JO - Nanomedicine: Nanotechnology, Biology, and Medicine
JF - Nanomedicine: Nanotechnology, Biology, and Medicine
SN - 1549-9634
M1 - 102346
ER -