{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Detering L"],"funding":["NIDDK NIH HHS","National Heart, Lung, and Blood Institute","NHLBI NIH HHS","National Science Foundation"],"pagination":["1386-1396"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC8737066"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["18(3)"],"pubmed_abstract":["Chemokines and chemokine receptors play an important role in the initiation and progression of atherosclerosis by mediating the trafficking of inflammatory cells. Chemokine receptor 5 (CCR5) has major implications in promoting the development of plaques to advanced stage and related vulnerability. CCR5 antagonist has demonstrated the effective inhibition of atherosclerotic progression in mice, making it a potential biomarker for atherosclerosis management. To accurately determine CCR5 <i>in vivo</i>, we synthesized CCR5 targeted Comb nanoparticles through a modular design and construction strategy with control over the physiochemical properties and functionalization of CCR5 targeting peptide d-Ala-peptide T-amide (DAPTA-Comb). <i>In vivo</i> pharmacokinetic evaluation through <sup>64</sup>Cu radiolabeling showed extended blood circulation of <sup>64</sup>Cu-DAPTA-Combs conjugated with 10%, 25%, and 40% DAPTA. The different organ distribution profiles of the three nanoparticles demonstrated the effect of DAPTA on not only physicochemical properties but also targeting efficiency. <i>In vivo</i> positron emission tomography/computed tomography (PET/CT) imaging in an apolipoprotein E knockout mouse atherosclerosis model (ApoE<sup>-/-</sup>) showed that the three <sup>64</sup>Cu-DAPTA-Combs could sensitively and specifically detect CCR5 along the progression of atherosclerotic lesions. In an ApoE-encoding adenoviral vector (AAV) induced plaque regression ApoE<sup>-/-</sup> mouse model, decreased monocyte recruitment, CD68+ macrophages, CCR5 expression, and plaque size were all associated with reduced PET signals, which not only further confirmed the targeting efficiency of <sup>64</sup>Cu-DAPTA-Combs but also highlighted the potential of these targeted nanoparticles for atherosclerosis imaging. Moreover, the up-regulation of CCR5 and colocalization with CD68+ macrophages in the necrotic core of <i>ex vivo</i> human plaque specimens warrant further investigation for atherosclerosis prognosis."],"journal":["Molecular pharmaceutics"],"pubmed_title":["CC Chemokine Receptor 5 Targeted Nanoparticles Imaging the Progression and Regression of Atherosclerosis Using Positron Emission Tomography/Computed Tomography."],"pmcid":["PMC8737066"],"funding_grant_id":["DMR-1720256","1R35HL145212","R01 HL125655","R00 HL138163","R01HL138163","R35 HL145212","P30 DK056341"],"pubmed_authors":["Williams JW","Randolph GJ","Heo GS","Gropler RJ","Elvington A","Detering L","Sultan D","Abdilla A","Liu Y","Luehmann HP","Woodard PK","Hawker CJ","Huang LH"],"additional_accession":[]},"is_claimable":false,"name":"CC Chemokine Receptor 5 Targeted Nanoparticles Imaging the Progression and Regression of Atherosclerosis Using Positron Emission Tomography/Computed Tomography.","description":"Chemokines and chemokine receptors play an important role in the initiation and progression of atherosclerosis by mediating the trafficking of inflammatory cells. Chemokine receptor 5 (CCR5) has major implications in promoting the development of plaques to advanced stage and related vulnerability. CCR5 antagonist has demonstrated the effective inhibition of atherosclerotic progression in mice, making it a potential biomarker for atherosclerosis management. To accurately determine CCR5 <i>in vivo</i>, we synthesized CCR5 targeted Comb nanoparticles through a modular design and construction strategy with control over the physiochemical properties and functionalization of CCR5 targeting peptide d-Ala-peptide T-amide (DAPTA-Comb). <i>In vivo</i> pharmacokinetic evaluation through <sup>64</sup>Cu radiolabeling showed extended blood circulation of <sup>64</sup>Cu-DAPTA-Combs conjugated with 10%, 25%, and 40% DAPTA. The different organ distribution profiles of the three nanoparticles demonstrated the effect of DAPTA on not only physicochemical properties but also targeting efficiency. <i>In vivo</i> positron emission tomography/computed tomography (PET/CT) imaging in an apolipoprotein E knockout mouse atherosclerosis model (ApoE<sup>-/-</sup>) showed that the three <sup>64</sup>Cu-DAPTA-Combs could sensitively and specifically detect CCR5 along the progression of atherosclerotic lesions. In an ApoE-encoding adenoviral vector (AAV) induced plaque regression ApoE<sup>-/-</sup> mouse model, decreased monocyte recruitment, CD68+ macrophages, CCR5 expression, and plaque size were all associated with reduced PET signals, which not only further confirmed the targeting efficiency of <sup>64</sup>Cu-DAPTA-Combs but also highlighted the potential of these targeted nanoparticles for atherosclerosis imaging. Moreover, the up-regulation of CCR5 and colocalization with CD68+ macrophages in the necrotic core of <i>ex vivo</i> human plaque specimens warrant further investigation for atherosclerosis prognosis.","dates":{"release":"2021-01-01T00:00:00Z","publication":"2021 Mar","modification":"2025-04-04T08:41:22.687Z","creation":"2025-04-04T08:41:22.687Z"},"accession":"S-EPMC8737066","cross_references":{"pubmed":["33591187"],"doi":["10.1021/acs.molpharmaceut.0c01183"]}}