Detection of atherosclerotic lesions and intimal macrophages using CD36-targeted nanovesicles

Shufang Nie, Jia Zhang, Raul Martinez-Zaguilan, Souad Sennoune, Md Nazir Hossen, Alice H. Lichtenstein, Jun Cao, Gary E. Meyerrose, Ralph Paone, Suthipong Soontrapa, Zhaoyang Fan, Shu Wang

Research output: Contribution to journalArticle

20 Scopus citations

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.

Original languageEnglish
Pages (from-to)61-70
Number of pages10
JournalJournal of Controlled Release
Volume220
DOIs
StatePublished - Dec 28 2015

Keywords

  • Atherosclerosis
  • CD36
  • Macrophages
  • Nanovesicles
  • Oxidized lipids
  • Targeted delivery

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    Nie, S., Zhang, J., Martinez-Zaguilan, R., Sennoune, S., Hossen, M. N., 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, 61-70. https://doi.org/10.1016/j.jconrel.2015.10.004