Abstract
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 Tb3+-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.
Highlights
Nanosized hydroxyapatite (HA), which possesses a high surface-to-volume ratio, high reactivity, and biomimetic morphology, has been proposed for a variety of biomedical applications, including drug delivery, gene transaction, cellular imaging, and biosensing [1,2,3,4]
If HA particles can migrate through the cell linings at the absorption site, how fast do they move through the body? Does the distribution of HA particles vary with the route of exposure? Are HA particles distributed evenly among all organs and tissues? These questions have great theoretical and clinical relevance for the safe and efficient application of HAs in biomedical applications
No peaks of impurity phases were identified in the X-ray diffraction (XRD) pattern of the HA-Tb nanorods, implying that the doped Tb3+ ions were incorporated into the HA lattice
Summary
Nanosized hydroxyapatite (HA), which possesses a high surface-to-volume ratio, high reactivity, and biomimetic morphology, has been proposed for a variety of biomedical applications, including drug delivery, gene transaction, cellular imaging, and biosensing [1,2,3,4]. Due to the interest in HA and HA-based nanomaterials for biomedical applications, their effects on biological systems have become a great concern. Buma et al reported wear particles originating from HA-coated hip prosthesis in the macrophages of the intertrabecular medullary space [9,10]. Tamaki et al found that wear particles originating from hip prosthesis enhanced the osteolytic potential of macrophages from bone marrow [11]. These findings support the hypothesis that HA is generally able to migrate away from the implantation site. These questions have great theoretical and clinical relevance for the safe and efficient application of HAs in biomedical applications If HA particles can migrate through the cell linings at the absorption site, how fast do they move through the body? Does the distribution of HA particles vary with the route of exposure? Are HA particles distributed evenly among all organs and tissues? These questions have great theoretical and clinical relevance for the safe and efficient application of HAs in biomedical applications
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