DC Field | Value | Language |
---|---|---|
dc.contributor.author | Yu, M. | ko |
dc.contributor.author | Ortega, C.A. | ko |
dc.contributor.author | Si, K. | ko |
dc.contributor.author | Molinaro, R. | ko |
dc.contributor.author | Schoen, F.J. | ko |
dc.contributor.author | Leitao, R.F.C. | ko |
dc.contributor.author | Xu, X. | ko |
dc.contributor.author | Mahmoudi, M. | ko |
dc.contributor.author | Ahn, S. | ko |
dc.contributor.author | Liu, J. | ko |
dc.contributor.author | Saw, P.E. | ko |
dc.contributor.author | Lee, I.-H. | ko |
dc.contributor.author | Brayner, M.M.B. | ko |
dc.contributor.author | Lotfi, A. | ko |
dc.contributor.author | Shi, J. | ko |
dc.contributor.author | Libby, P. | ko |
dc.contributor.author | Jon, Sangyong | ko |
dc.contributor.author | Farokhzad, O.C. | ko |
dc.date.accessioned | 2018-12-20T08:01:43Z | - |
dc.date.available | 2018-12-20T08:01:43Z | - |
dc.date.created | 2018-12-14 | - |
dc.date.created | 2018-12-14 | - |
dc.date.created | 2018-12-14 | - |
dc.date.issued | 2018-11 | - |
dc.identifier.citation | THERANOSTICS, v.8, no.21, pp.6008 - 6024 | - |
dc.identifier.issn | 1838-7640 | - |
dc.identifier.uri | http://hdl.handle.net/10203/248684 | - |
dc.description.abstract | Extra domain B of fibronectin (FN-EDB) is upregulated in the extracellular matrix during tissue remodeling and has been postulated as a potential biomarker for atherosclerosis, yet no systematic test for FN-EDB in plaques has been reported. We hypothesized that FN-EDB expression would intensify in advanced plaques. Furthermore, engineering of FN-EDB-targeted nanoparticles (NPs) could enable imaging/diagnosis and local delivery of payloads to plaques. Methods: The amount of FN-EDB in human atherosclerotic and normal arteries (ages: 40 to 85 years) was assessed by histological staining and quantification using an FN-EDB-specific aptide (APTFN-EDB). FN-EDB-specific NPs that could serve as MRI beacons were constructed by immobilizing APTFN-EDB on the NP surface containing DTPA[Gd]. MRI visualized APTFN-EDB-[Gd]NPs administered to atherosclerotic apolipoprotein E-deficient mice in the brachiocephalic arteries. Analysis of the ascending-to-descending thoracic aortas and the aortic roots of the mice permitted quantitation of Gd, FN-EDB, and APTFN-EDB-[Gd]NPs. Cyanine, a model small molecule drug, was used to study the biodistribution and pharmacokinetics of APTFN-EDB-NPs to evaluate their utility for drug delivery. Results: Atherosclerotic tissues had significantly greater FN-EDB-positive areas than normal arteries (P < 0.001). This signal pertained particularly to Type III (P < 0.01), IV (P < 0.01), and V lesions (P < 0.001) rather than Type I and II lesions (AHA classification). FN-EDB expression was positively correlated with macrophage accumulation and neoangiogenesis. Quantitative analysis of T1-weighted images of atherosclerotic mice revealed substantial APTFN-EDB-[Gd]NPs accumulation in plaques compared to control NPs, conventional MRI contrast agent (Gd-DTPA) or accumulation in wild-type C57BL/6J mice. Additionally, the APTFN-EDB-NPs significantly prolonged the blood-circulation time (t1/2: ~ 6 h) of a model drug and increased its accumulation in plaques (6.9-fold higher accumulation vs. free drug). Conclusions: Our findings demonstrate augmented FN-EDB expression in Type III, IV, and V atheromata and that APTFN-EDB-NPs could serve as a platform for identifying and/or delivering agents locally to a subset of atherosclerotic plaques. © Ivyspring International Publisher. | - |
dc.language | English | - |
dc.publisher | IVYSPRING INT PUBL | - |
dc.title | Nanoparticles targeting extra domain b of fibronectin− specific to the atherosclerotic lesion types III, IV, and v−enhance plaque detection and cargo delivery | - |
dc.type | Article | - |
dc.identifier.wosid | 000451946500016 | - |
dc.identifier.scopusid | 2-s2.0-85057156336 | - |
dc.type.rims | ART | - |
dc.citation.volume | 8 | - |
dc.citation.issue | 21 | - |
dc.citation.beginningpage | 6008 | - |
dc.citation.endingpage | 6024 | - |
dc.citation.publicationname | THERANOSTICS | - |
dc.identifier.doi | 10.7150/thno.24365 | - |
dc.contributor.localauthor | Jon, Sangyong | - |
dc.contributor.nonIdAuthor | Yu, M. | - |
dc.contributor.nonIdAuthor | Ortega, C.A. | - |
dc.contributor.nonIdAuthor | Si, K. | - |
dc.contributor.nonIdAuthor | Molinaro, R. | - |
dc.contributor.nonIdAuthor | Schoen, F.J. | - |
dc.contributor.nonIdAuthor | Leitao, R.F.C. | - |
dc.contributor.nonIdAuthor | Xu, X. | - |
dc.contributor.nonIdAuthor | Mahmoudi, M. | - |
dc.contributor.nonIdAuthor | Ahn, S. | - |
dc.contributor.nonIdAuthor | Liu, J. | - |
dc.contributor.nonIdAuthor | Saw, P.E. | - |
dc.contributor.nonIdAuthor | Lee, I.-H. | - |
dc.contributor.nonIdAuthor | Brayner, M.M.B. | - |
dc.contributor.nonIdAuthor | Lotfi, A. | - |
dc.contributor.nonIdAuthor | Shi, J. | - |
dc.contributor.nonIdAuthor | Libby, P. | - |
dc.contributor.nonIdAuthor | Farokhzad, O.C. | - |
dc.description.isOpenAccess | N | - |
dc.type.journalArticle | Article | - |
dc.subject.keywordAuthor | Aptides | - |
dc.subject.keywordAuthor | Atherosclerosis | - |
dc.subject.keywordAuthor | Extra domain B of fibronectin | - |
dc.subject.keywordAuthor | Magnetic resonance imaging | - |
dc.subject.keywordAuthor | Nanoparticles | - |
dc.subject.keywordPlus | SIRNA DELIVERY | - |
dc.subject.keywordPlus | HEART-DISEASE | - |
dc.subject.keywordPlus | ED-B | - |
dc.subject.keywordPlus | INFLAMMATION | - |
dc.subject.keywordPlus | MACROPHAGES | - |
dc.subject.keywordPlus | ANTIBODY | - |
dc.subject.keywordPlus | NEOVASCULARIZATION | - |
dc.subject.keywordPlus | NANOMEDICINE | - |
dc.subject.keywordPlus | MECHANISMS | - |
dc.subject.keywordPlus | CONJUGATE | - |
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