Journal
ACS APPLIED MATERIALS & INTERFACES
Volume 11, Issue 17, Pages 15316-15321Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acsami.9b02750
Keywords
nanoparticle; NPRC; atherosclerosis; positron emission tomography; translation
Funding
- Program of Excellence in Nanotechnology from the National Heart, Lung, and Blood Institute of the National Institutes of Health [HHSN268201000046C]
- MRSEC Program of the National Science Foundation [DMR-1720256]
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Nanoparticles have been assessed in preclinical models of atherosclerosis for detection of plaque complexity and treatment. However, their successful clinical translation has been hampered by less than satisfactory plaque detection and lack of a general strategy for assessing the translational potential of nanoparticles. Herein, nanoparticles based on comb-co-polymer assemblies were synthesized through a modular construction approach with precise control over the conjugation of multiple functional building blocks for in vivo evaluation. This high level of design control also allows physicochemical properties to be varied in a controllable fashion. Through conjugation of c-atrial natriuretic factor (CANE) peptide and radiolabeling with Cu-64, the Cu-64-CANF-comb nanoparticle was assessed for plaque imaging by targeting natriuretic peptide clearance receptor (NPRC) in a double-injury atherosclerosis model in rabbits. The prolonged blood circulation and enhanced binding capacity of Cu-64-CANF-comb nanoparticles provided sensitive and specific imaging of NPRC overexpressed in atherosclerotic lesions by positron emission tomography at intervals during the progression of the disease. Ex vivo tissue validation using autoradiography and immunostaining on human carotid endarterectomy specimens demonstrated specific binding of Cu-64-CANF-comb to human NPRC receptors. Taken together, this study not only shows the potential of NPRC-targeted Cu-64-CANF-comb nanoparticles for increased sensitivity to an epitope that increases during atherosclerosis plaque development but also provides a useful strategy for the general design and assessment of the translational potential of nanoparticles in cardiovascular imaging.
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