Table 4.

Detection and treatment of atherosclerosis using targeted nanoparticles via proteolysis, apoptosis and thrombosis processes

Molecular/ functional target	Nanoparticles	Imaging platforms	Animal model, dose and administration route	Results	Year and reference
Activated platelets	Versatile ultrasmall super paramagnetic iron oxide (VUSPIO) nanoparticles with recombinant human IgG4 antibody	MRI	In vitro human platelets; ex vivo human aorta samples; ApoE −/− mice; 10 µg/mL of antibody; I.V.	Nanoparticles bound to activated platelets.	2015136
Fibrin	Fibrin-binding peptides conjugated iron oxide nanoparticle–micelles (FibPep-ION- Micelles)	Magnetic particle imaging (MPI)	Human clots incubated with FibPep-ION- Micelles in vitro	Nanoparticles bound to the blood clot and gave a high signal.	2013134
Collapse of mitochondria l membrane potential during apoptosis	Synthetic biodegradable HDL- nanoparticles quantum dots	Optical imaging- fluorescence microscopy	RAW 264.7 macrophages, Male Sprague– Dawley rats; I.V.	Both in vivo and in vitro data revealed the increased detection of apoptotic cells. Synthetic biodegradable HDL- nanoparticles quantum dots targeted the collapse of mitochondrial membrane potential during apoptosis.	2013129
Activated platelets	Versatile ultrasmall superparamagnetic iron oxide (VUSPIO) particles, coupled to an anti-human P- selectin antibody (VH10)	MRI	Human platelets and endothelial cells; ApoE−/− mice. I.V.	VH10 bound to human activated platelets and endothelial cells.	2011135
Phosphatidyl serine on apoptotic cells and macrophages	Annexin A5- conjugated micellar nanoparticles carrying multiple Gd- labeled lipids and fluorescent lipids	MRI Fluorescence imaging	In vitro T- lymphoma cell line (Jurkat cells) at a concentration of 1 mM total lipid of nanoparticles; ApoE−/− mice, 2.5 µmol lipids per mouse; I.V.	Annexin A5-conjugated micellar nanoparticles targeted to apoptotic cells, and they detected PS-presenting cells in atherosclerotic lesions in apoE−/− mice.	2010128
Fibrin	Clot-binding peptide cysteine-arginine- glutamic acid-lysine- alanine (CREKA) bound micelles loaded with an anticoagulant drug hirulog	Fluorescence imaging	ApoE−/− mice; 100 µL of 1 mM micelles; I.V.	Micelles bound to unstable lesions in apoE−/− mice; Hirulog-loaded micelles had high hirulog concentrations and anti- thrombin activity in lesions.	2009133
Protease	Polymeric nanoparticles containing a protease sensor	Fluorescence molecular tomography (FMT) and CT	ApoE−/− mice; 5 nmol of protease sensor; I.V.	High signal intensity of nanoparticles was detected in the artery wall.	2009123
Phosphatidyl serine on apoptotic cells	Annexin V conjugated superparmagnetic iron oxide particles (SPIONs)	MRI	Watanabe heritable hyperlipidemic rabbits; SPIONs containing 0.05 mg of iron, I.V.	Annexin V conjugated SPIONs targeted to atherosclerotic lesions, but not healthy blood vessels.	2007127
Fibrin	Fibrin targeted (via anti-fibrin antibodies) Gd-DTPA-PE nanoparticles	MRI	Blood clots incubation	Gd-DTPA-PE nanoparticles modified with anti-fibrin antibodies had a high binding affinity to thrombi.	2003131

Notes:

ApoE−/−, apolipoprotein E null

CD44, cell surface adhesion molecule

Cy5.5, near-infrared (IR) fluorescence dye

CT, computed tomography

DTPA, diethylene-triamine-pentaacetic acid

Fe, iron

Gd, gadolinium

HDL, high-density lipoprotein

I.V., intravenous injection

MBq, megabecquerel as unit of radioactivity

MRI, magnetic resonance imaging

PE, phosphatidylethanolamine

PEG, polyethylene glycol

SPIONs , superparmagnetic iron oxide particles