Multi-modal in cellulo evaluation of NPR-C targeted C-ANF-peptide and C-ANF-comb nanoparticles

Monica Shokeen; Eric Pressly; Luke Connal; Yongjian Liu; Craig J. Hawker; Pamela K. Woodard; Carolyn J. Anderson; Samuel Achilefu; Michael J. Welch

doi:10.1117/12.914991

2 February 2012 Multi-modal in cellulo evaluation of NPR-C targeted C-ANF-peptide and C-ANF-comb nanoparticles

Monica Shokeen, Eric Pressly, Luke Connal, Yongjian Liu, Craig J. Hawker, Pamela K. Woodard, Carolyn J. Anderson, Samuel Achilefu, Michael J. Welch

Author Affiliations +

Proceedings Volume 8233, Reporters, Markers, Dyes, Nanoparticles, and Molecular Probes for Biomedical Applications IV; 82330U (2012) https://doi.org/10.1117/12.914991
Event: SPIE BiOS, 2012, San Francisco, California, United States

Abstract

Natriuretic peptides (NPs) are clinical markers of heart disease that have anti-proliferative and anti-migratory effects on vascular smooth-muscle cells (VSMCs). In atherosclerosis, NPs participate in vascular remodeling, where the expression of NP clearance receptors (NPR-Cs) is upregulated both in the endothelium and in VSMCs[1-3]. In this study, we investigated the enhanced targeting potential of novel multifunctional nanoprobes conjugated with multiple copies of a C-type atrial natriuretic factor (C-ANF) peptide fragment to target NPR-C transfected cells. The cell binding results of the NPR-C targeted nanoprobes were compared with that of the C-ANF peptide fragment alone. The nanoprobe and peptide structures contain the chelator DOTA (1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid) for labeling with the PET tracer, ⁶⁴Cu, for radioactive assays and luminescent Eu (III) for confocal cell imaging. Cell assays performed with the radioactive nanoprobe and peptide demonstrated higher cell binding of the targeted nanoprobe comapred with the peptide alone (8.63±1.67 vs. 1.13±0.06). The targeting specificity of both moieties was tested by using the control cell lines NPR-A and NPR-B, and receptor mediated uptake was demonstrated by reduced uptake in the presence of excess unlabeled respective probes.

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Monica Shokeen, Eric Pressly, Luke Connal, Yongjian Liu, Craig J. Hawker, Pamela K. Woodard, Carolyn J. Anderson, Samuel Achilefu, and Michael J. Welch "Multi-modal in cellulo evaluation of NPR-C targeted C-ANF-peptide and C-ANF-comb nanoparticles", Proc. SPIE 8233, Reporters, Markers, Dyes, Nanoparticles, and Molecular Probes for Biomedical Applications IV, 82330U (2 February 2012); https://doi.org/10.1117/12.914991

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KEYWORDS

Nanoparticles

Nanoprobes

Positron emission tomography

Receptors

Europium

Proteins

Confocal microscopy

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