Detection of macrophages via paramagnetic vesicles incorporating oxidatively tailored cholesterol ester: an approach for atherosclerosis imaging.
OBJECTIVE
Macrophages play a key role in the initiation, progression and complications of atherosclerosis. In this article we describe the synthesis of biocompatible, paramagnetic, fluorescent phosphatidylserine vesicles containing cholesterol ester with a free carboxylic acid function and its use for targeted imaging of macrophages.


RESULTS
We synthesized anionic vesicles containing a combination of phosphatidylserine and a novel synthetic oxidized cholesterol ester derivative (cholesterol-9-carboxynonanoate [9-CCN]). In vitro studies to characterize particle size, MRI relaxation times and stability were performed. Vesicles containing 9-CCN demonstrated enhanced ability to bind human low-density lipoprotein and to be internalized by macrophages. Experiments in cultured macrophages with 9-CCN vesicles, alone and in the presence of low-density lipoprotein, indicated uptake of vesicles through scavenger receptor and integrin-dependent pathways. In vivo MRI using 9-CCN vesicles containing gadolinium in a rabbit model of atherosclerosis revealed protracted enhancement of 9-CCN vesicles and colocalization with arterial macrophages not seen with control vesicles. Pharmacokinetic experiments demonstrated prolonged plasma residence time of 9-CCN vesicles, perhaps due to its capacity to bind to low-density lipoprotein.


CONCLUSIONS
Vesicles containing 9-CCN demonstrate prolonged plasma and plaque retention in experimental atherosclerosis. Such a strategy may represent a simple yet clinically relevant approach for macrophage imaging.
Davis Heart & Lung Research Institute, Room 110, 473 W 12th Avenue, Columbus, OH 43210-1252, USA.
Andrei
A
Maiseyeu
Georgeta
G
Mihai
Sashwati
S
Roy
Nisharahmed
N
Kherada
Orlando P
OP
Simonetti
Chandan K
CK
Sen
Qinghua
Q
Sun
Sampath
S
Parthasarathy
Sanjay
S
Rajagopalan
D000818:Animals; D050197:Atherosclerosis / Q000175:diagnosis*; D002478:Cells, Cultured; D002788:Cholesterol Esters / Q000737:chemistry*; D003287:Contrast Media / Q000138:chemical synthesis / Q000737:chemistry*; D006801:Humans; D007150:Immunohistochemistry; D008077:Lipoproteins, LDL / Q000737:chemistry; D008081:Liposomes / Q000138:chemical synthesis / Q000737:chemistry*; D008264:Macrophages / Q000166:cytology* / Q000378:metabolism*; D008279:Magnetic Resonance Imaging / Q000379:methods*; D018613:Microscopy, Confocal; D011817:Rabbits
D002788:Cholesterol Esters; D003287:Contrast Media; D008077:Lipoproteins, LDL; D008081:Liposomes