Journal
INTERNATIONAL JOURNAL OF PHARMACEUTICS
Volume 581, Issue -, Pages -Publisher
ELSEVIER
DOI: 10.1016/j.ijpharm.2020.119282
Keywords
Squalene-based nanoparticles; ApoE(-/-) mice; Atherosclerotic plaque detection; Plaque imaging
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Funding
- Agence Nationale de la Recherche, France [ANR-16-ENM2-0005-01]
- la Fondation pour la Recherche Medicale (FRM) France [ECO20160736101]
- Agence Nationale de la Recherche (ANR) [ANR-16-ENM2-0005] Funding Source: Agence Nationale de la Recherche (ANR)
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Native low-density lipoproteins (LDL) naturally accumulate at atherosclerotic lesions and are thought to be among the main drivers of atherosclerosis progression. Numerous nanoparticular systems making use of recombinant lipoproteins have been developed for targeting atherosclerotic plaque. These innovative formulations often require complicated purification and synthesis procedures which limit their eventual translation to the clinics. Recently, squalenoylation has appeared as a simple and efficient technique for targeting agents to endogenous lipoproteins through a bioconjugation approach. In this study, we have developed a fluorescent squalene bioconjugate to evaluate the biodistribution of squalene-based nanoparticles in an ApoE(-/-) model of atherosclerosis. By accumulating in LDL endogenous nanoparticles, the squalene bioconjugation could serve as an efficient targeting platform for atherosclerosis. Indeed, in this proof of concept, we show that our squalene-rhodamine (SQRho) nanoparticles, could accumulate in the aortas of atherosclerotic animals. Histological evaluation confirmed the presence of atherosclerotic lesions and the co-localization of SQRho bioconjugates at the lesion sites.
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