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Imaging specificity of MR-optical imaging agents following the masking of surface charge by poly(ethylene glycol).

Abstract：

:The 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 T2-weighted MR imaging. In vivo T2-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.

journal_name

Biomaterials

journal_title

Biomaterials

authors

Wu SC,Lin KL,Wang TP,Tzou SC,Singh G,Chen MH,Cheng TL,Chen CY,Liu GC,Lee TW,Hu SH,Wang YM

doi

10.1016/j.biomaterials.2013.02.025

subject

Has Abstract

pub_date

2013-05-01 00:00:00

pages

4118-4127

issue

16

eissn

0142-9612

issn

1878-5905

pii

S0142-9612(13)00194-4

journal_volume

34

pub_type

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