Liu Li, Hitchens T Kevin, Ye Qing, Wu Yijen, Barbe Brent, Prior Devin E, Li Wendy F, Yeh Fang-Cheng, Foley Lesley M, Bain Daniel J, Ho Chien
Department of Biological Sciences, Carnegie Mellon University, Pittsburgh, PA, USA.
Biochim Biophys Acta. 2013 Jun;1830(6):3447-53. doi: 10.1016/j.bbagen.2013.01.021. Epub 2013 Feb 8.
Superparamagnetic iron-oxide nanoparticles are useful as contrast agents for anatomical, functional and cellular MRI, drug delivery agents, and diagnostic biosensors. Nanoparticles are generally cleared by the reticuloendothelial system (RES), in particular taken up by Kupffer cells in the liver, limiting particle bioavailability and in-vivo applications. Strategies that decrease the RES clearance and prolong the circulation residence time of particles can improve the in-vivo targeting efficiency.
Intralipid 20.0%, an FDA approved nutritional supplement, was intravenously administered in rats at the clinical dose (2g/kg) 1h before intravenous injection of ultra-small superparamagnetic iron-oxide (USPIO) or micron-sized paramagnetic iron-oxide (MPIO) particles. Blood half-life, monocyte labeling efficiency, and particle biodistribution were assessed by magnetic resonance relaxometry, flow cytometry, inductively-coupled plasma MS, and histology.
Pre-treatment with Intralipid resulted in a 3.1-fold increase in USPIO blood half-life and a 2-fold increase in USPIO-labeled monocytes. A 2.5-fold increase in MPIO blood half-life and a 5-fold increase in MPIO-labeled monocytes were observed following Intralipid pre-treatment, with a 3.2-fold increase in mean iron content up to 2.60pg Fe/monocyte. With Intralipid, there was a 49.2% and 45.1% reduction in liver uptake vs. untreated controls at 48h for USPIO and MPIO, respectively.
Intralipid pre-treatment significantly decreases initial RES uptake and increases in-vivo circulation and blood monocyte labeling efficiency for nano- and micron-sized superparamagnetic iron-oxide particles.
Our findings can have broad applications for imaging and drug delivery applications, increasing the bioavailability of nano- and micron-sized particles for target sites other than the liver.
超顺磁性氧化铁纳米颗粒可用作解剖学、功能和细胞磁共振成像的造影剂、药物递送剂及诊断生物传感器。纳米颗粒通常由网状内皮系统（RES）清除，特别是被肝脏中的库普弗细胞摄取，这限制了颗粒的生物利用度及体内应用。降低RES清除率并延长颗粒循环驻留时间的策略可提高体内靶向效率。
在静脉注射超小超顺磁性氧化铁（USPIO）或微米级顺磁性氧化铁（MPIO）颗粒前1小时，以临床剂量（2g/kg）给大鼠静脉注射FDA批准的营养补充剂20.0%脂肪乳剂。通过磁共振弛豫测量法、流式细胞术、电感耦合等离子体质谱和组织学评估血液半衰期、单核细胞标记效率及颗粒生物分布。
脂肪乳剂预处理使USPIO血液半衰期增加3.1倍，USPIO标记的单核细胞增加2倍。脂肪乳剂预处理后，MPIO血液半衰期增加2.5倍，MPIO标记的单核细胞增加5倍，平均铁含量增加3.2倍，达到2.60pg铁/单核细胞。使用脂肪乳剂时，48小时时USPIO和MPIO的肝脏摄取量分别比未处理的对照组降低49.2%和45.1%。
脂肪乳剂预处理可显著降低RES的初始摄取，并提高纳米级和微米级超顺磁性氧化铁颗粒的体内循环及血液单核细胞标记效率。
我们的研究结果在成像和药物递送应用方面具有广泛的应用前景，可提高纳米级和微米级颗粒对肝脏以外靶部位的生物利用度。
