FMN-coated fluorescent iron oxide nanoparticles for RCP-mediated targeting and labeling of metabolically active cancer and endothelial cells
FMN-coated fluorescent iron oxide nanoparticles for RCP-mediated targeting and labeling of metabolically active cancer and endothelial cells
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DOI：
10.1016/j.biomaterials.2011.04.056
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发表时间：
2011-09-01
期刊：
影响因子：
14
通讯作者：
Gaetjens, Jessica
中科院分区：
文献类型：
--
作者：
Jayapaul, Jabadurai;Hodenius, Michael;Gaetjens, Jessica
核黄素是细胞代谢的必需维生素，在代谢活性细胞中高度上调。因此，靶向核黄素载体蛋白（RCP）可能是一个有前途的策略标记癌症和活化的内皮细胞。因此，超小型超顺磁性氧化铁纳米颗粒（USPIO）吸附性地涂覆有内源性RCP配体黄素单核苷酸（FMN），这使得它们具有靶向特异性和荧光性。使用各种物理化学表征技术（TEM、DLS、MRI和荧光光谱）评价所得FMN涂层USPIO（FLUSPIO）的芯直径、表面形态和表面覆盖率。使用三种不同的细胞活力试验（台盼蓝染色、7-AAD染色和TUNEL）证实了FLUSPIO的生物相容性。使用MRI和荧光显微镜对FLUSPIO进行的体外评价表明，癌细胞（PC-3、DU-145、LnCap）和活化内皮细胞（HUVEC）的标记效率较高。使用10倍和100倍过量游离FMN的竞争实验（使用MRI和ICP-MS）证实了PC-3细胞和HUVEC对FLUSPIO的RCP特异性摄取。因此，通过FMN的RCP靶向可能是使纳米颗粒荧光并增加癌症和活化内皮细胞的标记功效的优雅方式。FLUSPIO显示了这一点，由于其高T（2）-弛豫率，非常适合MR细胞跟踪实验和体内癌症检测。(C)2011爱思唯尔有限公司保留所有权利。
Riboflavin is an essential vitamin for cellular metabolism and is highly upregulated in metabolically active cells. Consequently, targeting the riboflavin carrier protein (RCP) may be a promising strategy for labeling cancer and activated endothelial cells. Therefore, Ultrasmall SuperParamagnetic Iron Oxide nanoparticles (USPIO) were adsorptively coated with the endogenous RCP ligand flavin mononucleotide (FMN), which renders them target-specific and fluorescent. The core diameter, surface morphology and surface coverage of the resulting FMN-coated USPIO (FLUSPIO) were evaluated using a variety of physicochemical characterization techniques (TEM, DLS, MRI and fluorescence spectroscopy). The biocompatibility of FLUSPIO was confirmed using three different cell viability assays (Trypan blue staining, 7-AAD staining and TUNEL). In vitro evaluation of FLUSPIO using MRI and fluorescence microscopy demonstrated high labeling efficiency of cancer cells (PC-3, DU-145, LnCap) and activated endothelial cells (HUVEC). Competition experiments (using MRI and ICP-MS) with a 10- and 100-fold excess of free FMN confirmed RCP-specific uptake of the FLUSPIO by PC-3 cells and HUVEC. Hence, RCP-targeting via FMN may be an elegant way to render nanoparticles fluorescent and to increase the labeling efficacy of cancer and activated endothelial cells. This was shown for FLUSPIO, which due to their high T(2)-relaxivity, are favorably suited for MR cell tracking experiments and cancer detection in vivo. (C) 2011 Elsevier Ltd. All rights reserved.