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Biodistribution and imaging of fluorescently-tagged iron oxide nanoparticles in a breast cancer mouse model

机译:荧光标记的氧化铁纳米粒子在乳腺癌小鼠模型中的生物分布和成像

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Iron oxide nanoparticle (IONP) hyperthermia is an emerging treatment that shows great potential as a cancer therapy both alone and in synergy with conventional modalities. Pre-clinical studies are attempting to elucidate the mechanisms of action and distributions of IONP in various in vitro and in vivo models, however these studies would greatly benefit from real-time imaging of IONP locations both in cellular and in mammalian systems. To this end, fluorescently-tagged IONP (flONP) have been employed for real time tracking and co-registration of IONP with iron content. Starch-coated IONP were fluorescently-tagged, purified and analyzed for fluorescent signal at various concentrations. flONP were incubated with MTGB cells for varying times and cellular uptake analyzed using confocal microscopy, flow cytometry and inductively-coupled plasma mass spectrometry (ICP-MS). flONP were also injected into a bilateral mouse tumor model for radiation modification of tumor tissue and enhanced flONP deposition assessed using a Xenogen IVIS fluorescent imager. Results demonstrated that flONP concentrations in vitro correlated with ICP-MS iron readings. flONP could be tracked in vitro as well as in tissue samples from an in vivo model. Future work will employ whole animal fluorescent imaging to track the biodistribution of flONP over time.
机译:氧化铁纳米粒子(IONP)热疗是一种新兴的治疗方法,无论是单独治疗还是与常规治疗相结合,均显示出巨大的癌症治疗潜力。临床前研究正在试图阐明IONP在各种体外和体内模型中的作用和分布机制,但是这些研究将极大地受益于细胞和哺乳动物系统中IONP位置的实时成像。为此,已经使用荧光标记的IONP(flONP)对IONP和铁含量进行实时跟踪和共配准。将淀粉包被的IONP荧光标记,纯化并分析各种浓度的荧光信号。将flONP与MTGB细胞孵育不同的时间,并使用共聚焦显微镜,流式细胞术和电感耦合等离子体质谱(ICP-MS)分析细胞摄取。将flONP也注射到双侧小鼠肿瘤模型中,以进行肿瘤组织的放射修饰,并使用Xenogen IVIS荧光成像仪评估flONP沉积的增强。结果表明,体外flONP浓度与ICP-MS铁读数相关。 flONP可以在体外以及体内模型的组织样本中进行追踪。未来的工作将采用全动物荧光成像技术来追踪flONP随时间的生物分布。

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