Physicochemical characterization of ferumoxytol, heparin and protamine nanocomplexes for improved magnetic labeling of stem cells.
Physicochemical characterization of ferumoxytol, heparin and protamine nanocomplexes for improved magnetic labeling of stem cells.
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DOI：
10.1016/j.nano.2016.07.011
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发表时间：
2017-02
期刊：
影响因子：
--
通讯作者：
Frank JA
中科院分区：
文献类型：
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作者：
Bryant LH Jr;Kim SJ;Hobson M;Milo B;Kovacs ZI;Jikaria N;Lewis BK;Aronova MA;Sousa AA;Zhang G;Leapman RD;Frank JA
基于干细胞的疗法已成为再生医学和治疗疾病的主要焦点。一种简单的方法，将三种药物肝素（H）、鱼精蛋白（P）和ferumoxytol（F）以纳米复合物（NC）的形式组合，有效地标记干细胞用于细胞MRI。我们报告的物理化学特性优化的H，P，和F组分在不同的比例，和混合序列，产生不同的流体动力学大小的NC。NC大小取决于药物在介质中混合的顺序。HPF或FHP的电子显微镜显示F位于球形HP复合物的表面。与具有相同浓度的F的HPF NC相比，与FHP NC孵育的人干细胞导致每个细胞的铁浓度显著更高。这些结果表明，FHP可能是有用的标记干细胞在临床上的翻译研究。通过将肝素（H）、鱼精蛋白（P）和ferumoxytol（F）或FHP以适当的浓度组合在一起，产生硬-软纳米复合物，其中HP（青色）在中心，F（橙子）涂覆在球状体的外部。从透射电子显微镜断层扫描倾斜系列获得的3D重建。比例尺= 250 nm。
Stem cell-based therapies have become a major focus in regenerative medicine and to treat diseases. A straightforward approach combining three drugs, heparin (H), protamine (P) with ferumoxytol (F) in the form of nanocomplexes (NCs) effectively labeled stem cells for cellular MRI. We report on the physicochemical characteristics for optimizing the H, P, and F components in different ratios, and mixing sequences, producing NCs that varied in hydrodynamic size. NC size depended on the order in which drugs were mixed in media. Electron microscopy of HPF or FHP showed that F was located on the surface of spheroidal shaped HP complexes. Human stem cells incubated with FHP NCs resulted in a significantly greater iron concentration per cell compared to that found in HPF NCs with the same concentration of F. These results indicate that FHP could be useful for labeling stem cells in translational studies in the clinic. By combining heparin (H), protamine (P) and ferumoxytol (F) or FHP together in appropriate concentrations results in hard-soft nanocomplexes in which HP (cyan) are in the center and F (orange) coats the outside of the spheroid. 3D reconstructions obtained from transmission electron microscopy tomographic tilt series. Scale bar =250nm.