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Detection of Intimal Macrophages in Atherosclerotic Lesions Using a CD36‐Targeted Ligand Containing Nanoparticle
Author(s) -
Dhanasekara Chathurika,
Zhang Jia,
Nie Shufang,
Wang Shu
Publication year - 2015
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.29.1_supplement.606.12
Subject(s) - cd36 , in vivo , fluorescence microscope , scavenger receptor , chemistry , in vitro , fluorescence , macrophage , pathology , ligand (biochemistry) , foam cell , receptor , microbiology and biotechnology , medicine , biochemistry , biology , cholesterol , lipoprotein , physics , quantum mechanics
Objective Atherosclerotic cardiovascular disease is the leading cause of death in the United States. Macrophages and lipid‐laden macrophages (foam cells) are the predominant immune cells in the lesions. We have synthesized biocompatible and biodegradable nanoparticles (NP), and we incorporated CD36‐targeting ligands on the surface of NP to make ligand‐NP (L‐NP). Our objective was to compare the target specificity of NP and L‐NP to macrophages in vitro and in LDL receptor null (LDL r‐/‐) mice. Methods: THP‐1 derived macrophages were incubated with florescence‐dye labeled NP and L‐NP and target specificity was measured using an EVOS ® Fluorescence Microscope. Six male 6 week old LDL r‐/‐ mice developed atherosclerotic lesions after feeding an atherogenic diet for 22 weeks. Fluorescence‐dye labeled NP or L‐NP were injected via tail veins. After 20 hours, fluorescence signals in aortic lesions were imaged in‐situ and in isolated aortas using an IVIS ® Lumina XR imaging system. Then dissected aortas were embedded in O.C.T. compound and serially sectioned. Fluorescence signals in cross‐sections of aortas were taken using an EVOS ® Fluorescence Microscope. Total Cy7 signal intensity in the cross‐sections of aortic lesions was analyzed using a NIH Image J software. Results: L‐NP as compared to NP had higher binding affinity to THP‐1 derived macrophagesIn‐vivo data showed that L‐NP had 1.4‐fold higher target specificity to aortic lesions than NP (p<0.001)Conclusion Our novel L‐NP has the potential for the prevention and treatment of atherosclerosis through targeting the macrophages in atherosclerotic lesions. Grant Funding Source: NIH 1R15AT007013‐01