Flexman Jennifer A, Cross Donna J, Lewellen Barbara L, Miyoshi Sosuke, Kim Yongmin, Minoshima Satoshi
Department of Bioengineering, University of Washington, Seattle, WA 98195-5061, USA.
IEEE Trans Nanobioscience. 2008 Sep;7(3):223-32. doi: 10.1109/TNB.2008.2002288.
Gene and drug therapy for organ-specific diseases in part depends on the efficient delivery to a particular region of the body. We examined the biodistribution of a viral envelope commonly used as a nanoscale gene delivery vehicle using positron emission tomography (PET) and investigated the magnetic alteration of its biodistribution. Iron oxide nanoparticles and (18)F-fluoride were encapsulated by hemagglutinating virus of Japan envelopes (HVJ-Es). HVJ-Es were then injected intravenously in the rat and imaged dynamically using high-resolution PET. Control subjects received injections of encapsulated materials alone. For magnetic targeting, permanent magnets were fixed on the head during the scan. Based on the quantitative analysis of PET images, HVJ-Es accumulated in the liver and spleen and activity remained higher than control subjects for 2 h. Histological sections of the liver confirmed imaging findings. Pixel-wise activity patterns on coregistered PET images of the head showed a significantly different pattern for the subjects receiving magnetic targeting as compared to all control groups. Imaging demonstrated the initial biodistribution of a viral envelope within the rodent by providing quantitative behavior over time and in specific anatomical regions. Magnetic force altered the biodistribution of the viral envelope to a target structure, and could enable region-specific delivery of therapeutic vehicles noninvasively.
针对器官特异性疾病的基因和药物治疗部分取决于能否有效地将其递送至身体的特定区域。我们使用正电子发射断层扫描(PET)研究了一种常用作纳米级基因递送载体的病毒包膜的生物分布,并研究了其生物分布的磁学改变。日本血凝病毒包膜(HVJ-Es)包裹了氧化铁纳米颗粒和(18)F-氟化物。然后将HVJ-Es静脉注射到大鼠体内,并使用高分辨率PET进行动态成像。对照受试者仅接受包裹材料的注射。为了进行磁靶向,在扫描过程中将永久磁铁固定在头部。基于PET图像的定量分析,HVJ-Es在肝脏和脾脏中蓄积,并且其活性在2小时内一直高于对照受试者。肝脏组织学切片证实了成像结果。与所有对照组相比,接受磁靶向的受试者在头部配准PET图像上的逐像素活性模式显示出明显不同的模式。成像通过提供随时间和在特定解剖区域的定量行为,展示了病毒包膜在啮齿动物体内的初始生物分布。磁力改变了病毒包膜向靶结构的生物分布,并能够无创地实现治疗载体的区域特异性递送。