TY - JOUR
T1 - Design and Modular Construction of a Polymeric Nanoparticle for Targeted Atherosclerosis Positron Emission Tomography Imaging
T2 - A Story of 25% 64Cu-CANF-Comb
AU - Woodard, Pamela K.
AU - Liu, Yongjian
AU - Pressly, Eric D.
AU - Luehmann, Hannah P.
AU - Detering, Lisa
AU - Sultan, Deborah E.
AU - Laforest, Richard
AU - McGrath, Alaina J.
AU - Gropler, Robert J.
AU - Hawker, Craig J.
N1 - Funding Information:
This work is supported by the National Heart, Lung and Blood Institute of the National Institutes of Health as a Program of Excellence in Nanotechnology (HHSN268201000046C). The characterization of nanoparticles was performed in the Central Facilities of the UCSB Materials Research Laboratory supported by the MRSEC Program of the National Science Foundation under award no. DMR1121053. No other potential conflict of interest relevant to this article was reported.
Publisher Copyright:
© 2016, Springer Science+Business Media New York.
PY - 2016/10/1
Y1 - 2016/10/1
N2 - Purpose: To assess the physicochemical properties, pharmacokinetic profiles, and in vivo positron emission tomography (PET) imaging of natriuretic peptide clearance receptors (NPRC) expressed on atherosclerotic plaque of a series of targeted, polymeric nanoparticles. Methods: To control their structure, non-targeted and targeted polymeric (comb) nanoparticles, conjugated with various amounts of c-atrial natriuretic peptide (CANF, 0, 5, 10 and 25%), were synthesized by controlled and modular chemistry. In vivo pharmacokinetic evaluation of these nanoparticles was performed in wildtype (WT) C57BL/6 mice after 64Cu radiolabeling. PET imaging was performed on an apolipoprotein E–deficient (ApoE−/−) mouse atherosclerosis model to assess the NPRC targeting efficiency. For comparison, an in vivo blood metabolism study was carried out in WT mice. Results: All three 64Cu-CANF-comb nanoparticles showed improved biodistribution profiles, including significantly reduced accumulation in both liver and spleen, compared to the non-targeted 64Cu-comb. Of the three nanoparticles, the 25% 64Cu-CANF-comb demonstrated the best NPRC targeting specificity and sensitivity in ApoE−/− mice. Metabolism studies showed that the radiolabeled CANF-comb was stable in blood up to 9 days. Histopathological analyses confirmed the up-regulation of NPRC along the progression of atherosclerosis. Conclusion: The 25% 64Cu-CANF-comb demonstrated its potential as a PET imaging agent to detect atherosclerosis progression and status.
AB - Purpose: To assess the physicochemical properties, pharmacokinetic profiles, and in vivo positron emission tomography (PET) imaging of natriuretic peptide clearance receptors (NPRC) expressed on atherosclerotic plaque of a series of targeted, polymeric nanoparticles. Methods: To control their structure, non-targeted and targeted polymeric (comb) nanoparticles, conjugated with various amounts of c-atrial natriuretic peptide (CANF, 0, 5, 10 and 25%), were synthesized by controlled and modular chemistry. In vivo pharmacokinetic evaluation of these nanoparticles was performed in wildtype (WT) C57BL/6 mice after 64Cu radiolabeling. PET imaging was performed on an apolipoprotein E–deficient (ApoE−/−) mouse atherosclerosis model to assess the NPRC targeting efficiency. For comparison, an in vivo blood metabolism study was carried out in WT mice. Results: All three 64Cu-CANF-comb nanoparticles showed improved biodistribution profiles, including significantly reduced accumulation in both liver and spleen, compared to the non-targeted 64Cu-comb. Of the three nanoparticles, the 25% 64Cu-CANF-comb demonstrated the best NPRC targeting specificity and sensitivity in ApoE−/− mice. Metabolism studies showed that the radiolabeled CANF-comb was stable in blood up to 9 days. Histopathological analyses confirmed the up-regulation of NPRC along the progression of atherosclerosis. Conclusion: The 25% 64Cu-CANF-comb demonstrated its potential as a PET imaging agent to detect atherosclerosis progression and status.
KW - atherosclerosis
KW - nanoparticle
KW - natriuretic peptide clearance receptor
KW - polymer synthesis
KW - positron emission tomography
UR - http://www.scopus.com/inward/record.url?scp=84973601106&partnerID=8YFLogxK
U2 - 10.1007/s11095-016-1963-8
DO - 10.1007/s11095-016-1963-8
M3 - Article
C2 - 27286872
AN - SCOPUS:84973601106
SN - 0724-8741
VL - 33
SP - 2400
EP - 2410
JO - Pharmaceutical Research
JF - Pharmaceutical Research
IS - 10
ER -