Department of Chemistry, The State Key Laboratory of Molecular Engineering of Polymers, Fudan University, 220 Handan Road, Shanghai 200433, China.
Department of Chemistry, The State Key Laboratory of Molecular Engineering of Polymers, Fudan University, 220 Handan Road, Shanghai 200433, China; Department of Biosynthesis, School of Pharmacy, Fudan University, Shanghai 201203, China.
Biomaterials. 2014 Mar;35(10):3348-55. doi: 10.1016/j.biomaterials.2013.12.064. Epub 2014 Jan 15.
Although nanoscale hydroxyapatite [Ca10(PO4)6(OH)2; HA] has been widely investigated as a carrier in the delivery of drugs, genes, or siRNA, the in vivo toxicity of nanoscale HA is not clear and the long-term dynamic distribution in vivo has not hitherto been visualized. In this work, gadolinium-doped HA nanorods (HA:Gd) with an r1 value of 5.49 s(-1) (mm)(-1) have been prepared by a hydrothermal method. Samarium-153 ((153)Sm) was then effectively post-labeled onto the HA:Gd ((153)Sm-HA:Gd) with a labeling rate of ∼100% and a radio-labeling stability in vitro of ∼100% over 48 h. The product could serve as a new dual-modality probe for SPECT and MR imaging in vivo. By means of SPECT and MRI, the HA:Gd nanorods were found to be quickly taken up by the mononuclear phagocyte system, especially the liver and spleen. The nanorods in the liver and lung tended to be eliminated within 24 h, but nanorods in the spleen behaved differently and proved difficult to excrete. In vitro studies by cell transmission electron microscopy (TEM) and methyl thiazolyl tetrazolium (MTT) assay showed good biocompatibility of the HA:Gd nanorods with HeLa cells, even at a high concentration. The indicators of body weight, histology, and serology demonstrated that the HA:Gd nanorods exhibited excellent biocompatibility in vivo for at least 61 days. Therefore, (153)Sm-HA:Gd nanorods with excellent relaxivity, γ-emission, and biosafety offer clear advantages and potential for bioapplications.
尽管纳米级羟基磷灰石 [Ca10(PO4)6(OH)2; HA] 已被广泛研究作为药物、基因或 siRNA 的载体，但纳米级 HA 的体内毒性尚不清楚，其在体内的长期动态分布也尚未被可视化。在这项工作中，通过水热法制备了 r1 值为 5.49 s(-1)（mm）(-1) 的掺钆羟基磷灰石纳米棒（HA:Gd）。然后，通过有效后标记，将钐-153（(153)Sm）（标记率约为 100%，体外放射标记稳定性约为 100%，超过 48 小时）标记到 HA:Gd（(153)Sm-HA:Gd）上。该产物可用作体内 SPECT 和 MR 成像的新的双模态探针。通过 SPECT 和 MRI 发现，HA:Gd 纳米棒很快被单核吞噬细胞系统吸收，特别是肝脏和脾脏。肝脏和肺部的纳米棒在 24 小时内趋于被清除，但脾脏中的纳米棒则不同，难以排出。细胞透射电子显微镜（TEM）和甲基噻唑基四唑（MTT）测定的体外研究表明，即使在高浓度下，HA:Gd 纳米棒与 HeLa 细胞也具有良好的生物相容性。体重、组织学和血清学指标表明，HA:Gd 纳米棒在体内至少 61 天具有优异的生物相容性。因此，具有优异弛豫率、γ发射和生物安全性的 (153)Sm-HA:Gd 纳米棒在生物应用中具有明显的优势和潜力。
