Detection of atherosclerotic lesions and intimal macrophages using CD36-targeted nanovesicles
| Autor: | Jia Zhang, Gary Meyerrose, Souad R. Sennoune, Raul Martinez-Zaguilan, Zhaoyang Fan, Suthipong Soontrapa, Ralph Paone, Jun Cao, Shu-Fang Nie, Nazir Hossen, Shu Wang, Alice H. Lichtenstein |
|---|---|
| Rok vydání: | 2015 |
| Předmět: |
CD36 Antigens
Male Pathology medicine.medical_specialty CD36 Pharmaceutical Science Inflammation Article Lesion Mice In vivo medicine Macrophage Animals Humans Receptor Cells Cultured biology business.industry Macrophages Atherosclerosis In vitro Lipoproteins LDL Mice Inbred C57BL Receptors LDL LDL receptor biology.protein Nanoparticles medicine.symptom business |
| Zdroj: | Journal of controlled release : official journal of the Controlled Release Society. 220 |
| ISSN: | 1873-4995 |
| Popis: | 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 macrophages 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. |
| Databáze: | OpenAIRE |
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