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dc.contributor.authorWu, Shou-Chengen_US
dc.contributor.authorLin, Kun-Liangen_US
dc.contributor.authorWang, Tzu-Pinen_US
dc.contributor.authorTzou, Shey-Cherngen_US
dc.contributor.authorSingh, Gyanen_US
dc.contributor.authorChen, Ming-Hungen_US
dc.contributor.authorCheng, Tian-Luen_US
dc.contributor.authorChen, Chiao-Yunen_US
dc.contributor.authorLiu, Gin-Chungen_US
dc.contributor.authorLee, Te-Weien_US
dc.contributor.authorHu, Shao-Hwaen_US
dc.contributor.authorWang, Yun-Mingen_US
dc.date.accessioned2014-12-08T15:30:13Z-
dc.date.available2014-12-08T15:30:13Z-
dc.date.issued2013-05-01en_US
dc.identifier.issn0142-9612en_US
dc.identifier.urihttp://dx.doi.org/10.1016/j.biomaterials.2013.02.025en_US
dc.identifier.urihttp://hdl.handle.net/11536/21655-
dc.description.abstractThe coupling of specific antibodies to imaging agents often improves imaging specificity. However, free amine groups designed for the coupling can cause nonspecific binding of the imaging agents. We report here development of a nanocarrier, MnMEIO-silane-NH2-mPEG nanoparticles (NPs), consisting of a manganese-doped iron oxide nanoparticle core (MnMEIO), a copolymer shell of silane and amine-functionalized poly(ethylene glycol) (silane-EA-mPEG). The key feature in MnMEIO-silane-NH2-mPEG is the flexible PEG, which masks the non-conjugated reactive amine groups (-NH2 <-> -NH3+) and reduces nonspecific binding of MnMEIO-silane-NH2-mPEG to cells. The amine groups on MnMEIO-silane-NH2-mPEG were conjugated with the fluorescent dye, Cy777 or antibodies [Erbitux (Erb)] to form a MR-optical imaging contrast agent (MnMEIO-silane-NH2-(Erb)-mPEG) for EGFR-expressing tumors. Confocal microscopic and flow cytometric analyses showed that MnMEIO-silane-NH2-(Erb)-mPEG displayed low nonspecific binding. Moreover, TEM images showed that MnMEIO-silane-NH2-(Erb)-mPEG were endocytosed by EGFR-expressing cells. In line with their EGFR expression levels, A431, PC-3, and Colo-205 tumors treated with MnMEIO-silane-NH2-(Erb)-mPEG NPs showed -97.1%, -49.7%, and -2.8% contrast enhancement, respectively, in in vitro T-2-weighted MR imaging. In vivo T-2-weighted MR imaging and optical images showed that MnMEIO-silane-NH2-(Erb)mPEG could specifically and effectively target to EGFR-expressing tumors in nude mice; the relative contrast enhancements were 7.94 (at 2 h) and 7.59 (at 24 h) fold higher in A431 tumors as compared to the EGFR-negative Colo-205 tumors. On the contrary, MnMEIO-silane-NH2-(Erb) NPs showed only 1.44 (at 2 h) and 1.52 (at 24 h) fold higher in EGFR-positive tumors as compared to the EGFR-negative tumors. Finally, antibodies can be readily changed to allow imaging of other tumors bearing different antigens. These data indicate that masking surface charges on contrast agents is a useful strategy to improve imaging efficacy. (c) 2013 Elsevier Ltd. All rights reserved.en_US
dc.language.isoen_USen_US
dc.subjectEGFRen_US
dc.subjectErbituxen_US
dc.subjectMnMEIOen_US
dc.subjectMRIen_US
dc.subjectNanocarrieren_US
dc.titleImaging specificity of MR-optical imaging agents following the masking of surface charge by poly(ethylene glycol)en_US
dc.typeArticleen_US
dc.identifier.doi10.1016/j.biomaterials.2013.02.025en_US
dc.identifier.journalBIOMATERIALSen_US
dc.citation.volume34en_US
dc.citation.issue16en_US
dc.citation.spage4118en_US
dc.citation.epage4127en_US
dc.contributor.department生物科技學系zh_TW
dc.contributor.departmentDepartment of Biological Science and Technologyen_US
dc.identifier.wosnumberWOS:000317322600019-
dc.citation.woscount6-
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