Wang Ping, Ross Alana, Yoo Byunghee, Yang Jingsheng, Farrar Christian, Ran Chongzhao, Pantazopoulos Pamela, Medarova Zdravka, Moore Anna
Molecular Imaging Laboratory, MGH/MIT/HMS Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA.
MGH/MIT/HMS Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA.
Diabetes Metab Res Rev. 2017 Jul;33(5). doi: 10.1002/dmrr.2881. Epub 2017 Feb 23.
The absence of reliable drug delivery systems to pancreatic islet cells hampers efficient treatment of type 1 diabetes. Nanoparticle delivery systems equipped with imaging capabilities could enable selective delivery to pancreatic islet cells. Biodistribution of nanoparticles is defined by several factors including the mode of administration, which determines accumulation in various organs.
In this study, we tested whether intrapancreatic ductal injection of magnetic nanoparticles would result in efficient cellular uptake by pancreatic islet cells. Dextran-coated iron oxide nanoparticles labeled with the near infrared fluorescent dye Cy5.5 were injected into the intrapancreatic ducts of streptozotocin-induced diabetic and healthy mice. To monitor the distribution of the nanoparticles, we performed in vivo magnetic resonance imaging followed by optical imaging and histology.
Both imaging modalities demonstrated accumulation of the nanoparticles in the pancreas. However, histology revealed a high accumulation of nanoparticles in the insulin-producing cells in the pancreata of diabetic animals. By contrast, in nondiabetic controls, nanoparticles were mainly restricted to nonendocrine tissues.
Our results demonstrate that pancreatic ductal injection accompanied by image guidance could serve as an alternative pathway for nanoparticle delivery. We expect to utilize this intraductal delivery method for theranostic applications in type 1 diabetes.
缺乏可靠的胰岛细胞药物递送系统阻碍了1型糖尿病的有效治疗。具备成像能力的纳米颗粒递送系统能够实现对胰岛细胞的选择性递送。纳米颗粒的生物分布由多种因素决定,包括给药方式,而给药方式决定了纳米颗粒在各个器官中的蓄积情况。
在本研究中,我们测试了经胰管注射磁性纳米颗粒是否会导致胰岛细胞有效摄取。将用近红外荧光染料Cy5.5标记的葡聚糖包被的氧化铁纳米颗粒注射到链脲佐菌素诱导的糖尿病小鼠和健康小鼠的胰管中。为监测纳米颗粒的分布,我们先进行了体内磁共振成像,随后进行光学成像和组织学检查。
两种成像方式均显示纳米颗粒在胰腺中蓄积。然而,组织学检查发现纳米颗粒在糖尿病动物胰腺的胰岛素生成细胞中高度蓄积。相比之下,在非糖尿病对照组中,纳米颗粒主要局限于非内分泌组织。
我们的结果表明,在图像引导下经胰管注射可作为纳米颗粒递送的一种替代途径。我们期望将这种导管内递送方法用于1型糖尿病的诊疗应用。