|Nie, Shufan - Texas Tech University|
|Zhang, Jia - Texas Tech University|
|Martinez-zaguilan, Raul - Texas Tech University|
|Sennoune, Souad - Texas Tech University|
|Hossen, Md Nazir - Texas Tech University|
|Lichtenstein, Alice - Jean Mayer Human Nutrition Research Center On Aging At Tufts University|
|Cao, Jun - Texas Tech University|
|Meyerrose, Gary - Texas Tech University|
|Paone, Ralph - Texas Tech University|
|Soontrapa, Suthipong - Texas Tech University|
|Fan, Zhaoyon - Texas Tech University|
|Wang, Shu - Texas Tech University|
Submitted to: Journal of Controlled Release
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 10/1/2015
Publication Date: 10/9/2015
Citation: Nie, S., Zhang, J., Martinez-Zaguilan, R., Sennoune, S., Hossen, M., Lichtenstein, A.H., Cao, J., Meyerrose, G.E., Paone, R., Soontrapa, S., Fan, Z., Wang, S. 2015. Detection of atherosclerotic lesions and intimal macrophages using CD36-targeted nanovesicles. Journal of Controlled Release. 220(A):61-70. doi: 10.1016/j.jconrel.2015.10.004.
Interpretive Summary: Current approaches to determine the location of atherosclerotic plaque, the primary cause of heart disease, are limited. This limitation impacts on treatment options. One way to improve the ability to determine the location of plaque is to create a particle that when introduced into the blood stream would specifically bind to the affected area. We took advantage of the findings that a certain blood cell type, macrophages, accumulates in atherosclerosis plaque. The presence of these cells is positively associated with lesion progression, severity and destabilization. The objective of this study was to create nanovesicles with specific affinity for atherosclerotic plaque, specifically targeting the CD36 receptor, a scavenger receptor family of cell surface proteins. Soy phosphatidylcholine was used to synthesize the nanovesicles, incorporating 1-(palmitoyl)-2-(5-keto-6-octene-dioyl) phosphatidylcholine on their surface to target the CD36 receptor (termed targeted nanovesicles). The in vitro data demonstrated that these targeted nanovesicles were recognized by macrophages. Mouse in vivo studies demonstrated that these targeted nanovesicles co-localized with macrophages in the atherosclerosis plaque. Hence, these targeted nanovesicles may facilitate the in vivo noninvasive imaging of atherosclerotic lesions in terms of intimal macrophages accumulation and distribution and disclose lesion features related to inflammation and possibly vulnerability, thereby facilitate early lesion detection and treatment.
Technical Abstract: Current approaches to the diagnosis and therapy of atherosclerosis cannot target to 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.