Department of Geriatric Dentistry, National Engineering Laboratory for Digital and Material Technology of Stomatology, Beijing Laboratory of Biomedical Materials, Peking University School and Hospital of Stomatology, Peking University, Beijing 100081, China.
Department of Biomedical Engineering, College of Engineering, Peking University, 5 Yiheyuan Road, Haidian District, 100871 Beijing, China.
Molecules. 2017 Jun 23;22(7):1043. doi: 10.3390/molecules22071043.
With the increasing interest in hydroxyapatite (HA) nanostructures for use in biomedicine, the systematic evaluation of their potential effects on biological systems is becoming critically important. In this work, we report the in vitro cellular uptake, in vivo tissue distributions and toxicity of Tb-doped HA (HA-Tb) after short-, intermediate-, and long-term exposure. Transmission electron microscopy analysis indicated that HA-Tb was taken up by cells via vesicle endocytosis. Cell proliferation and cytotoxicity assay, combined with confocal laser scanning microscopy, indicated excellent cell viability with no changes in cell morphology at the examined doses. Three HA-Tb delivery methods (intraperitoneal, intragastric, and intravenous) resulted in similar time-dependent tissue distributions, while intraperitoneal injection produced the highest bioavailability. HA-Tb initially accumulated in livers and intestines of rats (4 h to one day after administration), then became increasingly distributed in the kidney and bladder (seven days), and finally decreased in all tissues after 30 to 90 days. No histopathological abnormalities or lesions related to treatment with HA-Tb were observed. These results suggest that HA-Tb has minimal in vitro and in vivo toxicity, regardless of the delivery mode, time, and dose. The findings provide a foundation for the design and development of HA for biological applications.
随着人们对羟基磷灰石（HA）纳米结构在生物医学中应用的兴趣日益增加，对其对生物系统潜在影响的系统评估变得至关重要。在这项工作中，我们报告了 Tb 掺杂 HA（HA-Tb）在短期、中期和长期暴露后的体外细胞摄取、体内组织分布和毒性。透射电子显微镜分析表明，HA-Tb 通过囊泡内吞作用被细胞摄取。细胞增殖和细胞毒性测定，结合共聚焦激光扫描显微镜，表明在研究剂量下细胞活力良好，细胞形态无变化。三种 HA-Tb 给药方式（腹腔内、胃内和静脉内）导致相似的时间依赖性组织分布，而腹腔内注射产生最高的生物利用度。HA-Tb 最初在大鼠的肝脏和肠道中积累（给药后 4 小时至一天），然后在肾脏和膀胱中分布越来越多（七天），最后在 30 至 90 天后在所有组织中减少。未观察到与 HA-Tb 治疗相关的组织病理学异常或病变。这些结果表明，HA-Tb 无论给药方式、时间和剂量如何，都具有最小的体外和体内毒性。这些发现为生物应用中 HA 的设计和开发提供了基础。
