title: Detection of atherosclerotic lesions and intimal macrophages using CD36-targeted nanovesicles.
abstract: Current approaches to the diagnosis and therapy of atherosclerosis cannot target lesion-determinant cells in the artery wall. Intimal macrophage infiltration promotes atherosclerotic lesion development by facilitating the accumulation of oxidized low-density lipoproteins (oxLDL) and increasing inflammatory responses. The presence of these cells is positively associated with lesion progression, severity and destabilization. Hence, they are an important diagnostic and therapeutic target. The objective of this study was to noninvasively assess the distribution and accumulation of intimal macrophages using CD36-targeted nanovesicles. Soy phosphatidylcholine was used to synthesize liposome-like nanovesicles. 1-(Palmitoyl)-2-(5-keto-6-octene-dioyl) phosphatidylcholine was incorporated on their surface to target the CD36 receptor. All in vitro data demonstrate that these targeted nanovesicles had a high binding affinity for the oxLDL binding site of the CD36 receptor and participated in CD36-mediated recognition and uptake of nanovesicles by macrophages. Intravenous administration into LDL receptor null mice of targeted compared to non-targeted nanovesicles resulted in higher uptake in aortic lesions. The nanovesicles co-localized with macrophages and their CD36 receptors in aortic lesions. This molecular target approach may facilitate the in vivo noninvasive imaging of atherosclerotic lesions in terms of intimal macrophage accumulation and distribution and disclose lesion features related to inflammation and possibly vulnerability thereby facilitate early lesion detection and targeted delivery of therapeutic compounds to intimal macrophages.
authors.affiliation: Department of Nutritional Sciences, Texas Tech University, Lubbock, TX 79409, USA.
authors.forename: Shufang
authors.initials: S
authors.lastname: Nie
authors.affiliation: Department of Nutritional Sciences, Texas Tech University, Lubbock, TX 79409, USA.
authors.forename: Jia
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Cell Physiology and Molecular Biophysics, Texas Tech University Health Sciences Center, Lubbock, TX 79416, USA.
authors.forename: Raul
authors.initials: R
authors.lastname: Martinez-Zaguilan
authors.affiliation: Department of Cell Physiology and Molecular Biophysics, Texas Tech University Health Sciences Center, Lubbock, TX 79416, USA.
authors.forename: Souad
authors.initials: S
authors.lastname: Sennoune
authors.affiliation: Department of Nutritional Sciences, Texas Tech University, Lubbock, TX 79409, USA.
authors.forename: Md Nazir
authors.initials: MN
authors.lastname: Hossen
authors.affiliation: Cardiovascular Nutrition Laboratory, Jean Mayer Human Nutrition Research Center on Aging, Tufts University, Boston, MA 02111, USA.
authors.forename: Alice H
authors.initials: AH
authors.lastname: Lichtenstein
authors.affiliation: Department of Nutritional Sciences, Texas Tech University, Lubbock, TX 79409, USA; State Key Laboratory of Food Science and Technology, Nanchang University, Nanchang 330047, Jiangxi, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Cao
authors.affiliation: Division of Cardiology, Department of Internal Medicine, Texas Tech University Health Sciences Center, Lubbock, TX 79430, USA.
authors.forename: Gary E
authors.initials: GE
authors.lastname: Meyerrose
authors.affiliation: Department of Surgery, Texas Tech University Health Sciences Center, Lubbock, TX 79430, USA.
authors.forename: Ralph
authors.initials: R
authors.lastname: Paone
authors.affiliation: Division of Cardiology, Department of Internal Medicine, Texas Tech University Health Sciences Center, Lubbock, TX 79430, USA.
authors.forename: Suthipong
authors.initials: S
authors.lastname: Soontrapa
authors.affiliation: Department of Electrical and Computer Engineering and Nano Tech Center, Texas Tech University, Lubbock, TX 79409, USA.
authors.forename: Zhaoyang
authors.initials: Z
authors.lastname: Fan
authors.affiliation: Department of Nutritional Sciences, Texas Tech University, Lubbock, TX 79409, USA. Electronic address: shu.wang@ttu.edu.
authors.forename: Shu
authors.initials: S
authors.lastname: Wang
mesh_terms: D000818:Animals; D050197:Atherosclerosis / Q000175:diagnosis*; D018955:CD36 Antigens / Q000378:metabolism*; D002478:Cells, Cultured; D006801:Humans; D008077:Lipoproteins, LDL / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D053758:Nanoparticles / Q000737:chemistry*; D011973:Receptors, LDL / Q000502:physiology
chemical_list: D018955:CD36 Antigens; D008077:Lipoproteins, LDL; D011973:Receptors, LDL; C099252:oxidized low density lipoprotein
keywords: Atherosclerosis; CD36; Macrophages; Nanovesicles; Oxidized lipids; Targeted delivery