MRI of breast tumor initiating cells using the extra domain-B of fibronectin targeting nanoparticles.
MRI of breast tumor initiating cells using the extra domain-B of fibronectin targeting nanoparticles.
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作者：
Sun Y;Kim HS;Park J;Li M;Tian L;Choi Y;Choi BI;Jon S;Moon WK
乳腺肿瘤起始细胞(BTICs)的鉴定对乳腺癌的诊断和治疗具有重要意义。本研究旨在探讨额外的纤维连接蛋白B结构域(EDB-FN)能否作为BTICs的新的生物标志物，以及靶向超顺磁性氧化铁纳米颗粒(SPIONS)的EDB-FN是否可用于体内外BTIC的磁共振成像(MRI)造影剂。而非BTIC(MCF-7、BT-474、SUM-225、MDA-MB-231)则不表达EDB-FN。此外，Cy3.3标记的EDB-FN特异性多肽(APTEDB)显示出与靶细胞Ndy-1的优先结合。为了构建EDB-FN靶向成像探针，将APTEDB共价连接到热交联SPION(TCL-SPION)上，得到APTEDB-TCL-SPION。在细胞模型的体外磁共振成像中，APTEDB-TCL-Spion与NDY-1细胞有明显的选择性结合，而在MCF-7细胞中几乎没有观察到结合。在NDY-1小鼠移植瘤模型中静脉注射APTEDB-TCL-Spion后，在T2加权像上肿瘤内的信号明显减少，而非靶向SPION如APTscurble-TCL-Spion或TCL-Spion的信号仅有轻微变化。综上所述，我们首次报道EDB-FN在BTIC中大量表达，因此可能作为一种新的生物标志物用于识别BTIC。我们的研究还表明APTEDB-TCL-SPION可以作为BTIC成像的MRI造影剂。
The identification of breast tumor initiating cells (BTICs) is important for the diagnosis and therapy of breast cancers. This study was undertaken to evaluate whether the extra domain-B of fibronectin (EDB-FN) could be used as a new biomarker for BTICs and whether EDB-FN targeting superparamagnetic iron oxide nanoparticles (SPIONs) could be used as a magnetic resonance imaging (MRI) contrast agent for BTIC imaging in vitro and in vivo. BTICs (NDY-1) exhibited high EDB-FN expression, whereas non-BTICs (MCF-7, BT-474, SUM-225, MDA-MB-231) did not exhibit EDB-FN expression. Furthermore, Cy3.3-labeled EDB-FN specific peptides (APTEDB) showed preferential binding to the targeted NDY-1 cells. To construct an EDB-FN targeted imaging probe, APTEDB was covalently attached to a thermally cross-linked SPION (TCL-SPION) to yield APTEDB-TCL-SPION. In the in vitro MRI of cell phantoms, selective binding of APTEDB-TCL-SPION to NDY-1 cells was evident, but little binding was observed in MCF-7 cells. After the intravenous injection of APTEDB-TCL-SPION into the NDY-1 mouse tumor xenograft model, a significant decrease in the signal within the tumor was observed in the T2*-weighted images; however, there was only a marginal change in the signal of non-targeting SPIONs such as APTscramble-TCL-SPION or TCL-SPION. Taken together, we report for the first time that EDB-FN was abundantly expressed in BTICs and may therefore be useful as a new biomarker for identifying BTICs. Our study also suggests that APTEDB-TCL-SPION could be used as an MRI contrast agent for BTIC imaging.
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影响因子：
3.7
作者：
Choi Y;Kim HS;Cho KW;Lee KM;Yi YJ;Eun SJ;Kim HJ;Woo J;Choi SH;Whangbo TK;Choi C;Noh DY;Moon WK
通讯作者：
Moon WK
DOI：
10.1073/pnas.1006732107
发表时间：
2010-10-19
影响因子：
11.1
作者：
Liu, Huiping;Patel, Manishkumar R.;Clarke, Michael F.
通讯作者：
Clarke, Michael F.
影响因子：
15
作者：
Lee, Haerim;Yu, Mi Kyung;Jon, Sangyong
通讯作者：
Jon, Sangyong
影响因子：
7.5
作者：
POTTS, JR;CAMPBELL, ID
通讯作者：
CAMPBELL, ID
影响因子：
16.6
作者：
Kim, Sunghyun;Kim, Daejin;Jon, Sangyong
通讯作者：
Jon, Sangyong