Potential Clinical Risk of Inflammation and Toxicity from Rare-Earth Nanoparticles in Mice.

BACKGROUND: Nanotechnology is emerging as a promising tool to perform noninvasive therapy and optical imaging. However, nanomedicine may pose a potential risk of toxicity during in vivo applications. In this study, we aimed to investigate the potential toxicity of rare-earth nanoparticles (RENPs) using mice as models. METHODS: We synthesized RENPs through a typical co-precipitation method. Institute of Cancer Research (ICR) mice were randomly divided into seven groups including a control group and six experimental groups (10 mice per group). ICR mice were intravenously injected with bare RENPs at a daily dose of 0, 0.5, 1.0, and 1.5 mg/kg for 7 days. To evaluate the toxicity of these nanoparticles in mice, magnetic resonance imaging (MRI) was performed to assess their uptake in mice. In addition, hematological and biochemical analyses were conducted to evaluate any impairment in the organ functions of ICR mice. The analysis of variance (ANOVA) followed by a one-way ANOVA test was used in this study. A repeated measures' analysis was used to determine any significant differences in white blood cell (WBC), alanine aminotransferase (ALT), and creatinine (CREA) levels at different evaluation times in each group. RESULTS: We demonstrated the successful synthesis of two different sizes (10 nm and 100 nm) of RENPs. Their physical properties were characterized by transmission electron microscopy and a 980 nm laser diode. Results of MRI study revealed the distribution and circulation of the RENPs in the liver. In addition, the hematological analysis found an increase of WBCs to (8.69 ± 0.85) × 109/L at the 28th day, which is indicative of inflammation in the mouse treated with 1.5 mg/kg NaYbF4:Er nanoparticles. Furthermore, the biochemical analysis indicated increased levels of ALT ([64.20 ± 15.50] U/L) and CREA ([27.80 ± 3.56] µmol/L) at the 28th day, particularly those injected with 1.5 mg/kg NaYbF4:Er nanoparticles. These results suggested the physiological and pathological damage caused by these nanoparticles to the organs and tissues of mice, especially to liver and kidney. CONCLUSION: The use of bare RENPs may cause possible hepatotoxicity and nephritictoxicity in mice.

Rare-earth Nanoparticle-induced Cytotoxicity on Spatial Cognition Memory of Mouse Brain.

BACKGROUND: Luminescent rare-earth-based nanoparticles have been increasingly used in nanomedicine due to their excellent physicochemical properties, such as biomedical imaging agents, drug carriers, and biomarkers. However, biological safety of the rare-earth-based nanomedicine is of great significance for future development in practical applications. In particular, biological effects of rare-earth nanoparticles on human's central nervous system are still unclear. This study aimed to investigate the potential toxicity of rare-earth nanoparticles in nervous system function in the case of continuous exposure. METHODS: Adult ICR mice were randomly divided into seven groups, including control group (receiving 0.9% normal saline) and six experimental groups (10 mice in each group). Luminescent rare-earth-based nanoparticles were synthesized by a reported co-precipitation method. Two different sizes of the nanoparticles were obtained, and then exposed to ICR mice through caudal vein injection at 0.5, 1.0, and 1.5 mg/kg body weight in each day for 7 days. Next, a Morris water maze test was employed to evaluate impaired behaviors of their spatial recognition memory. Finally, histopathological examination was implemented to study how the nanoparticles can affect the brain tissue of the ICR mice. RESULTS: Two different sizes of rare-earth nanoparticles have been successfully obtained, and their physical properties including luminescence spectra and nanoparticle sizes have been characterized. In these experiments, the rare-earth nanoparticles were taken up in the mouse liver using the magnetic resonance imaging characterization. Most importantly, the experimental results of the Morris water maze tests and histopathological analysis clearly showed that rare-earth nanoparticles could induce toxicity on mouse brain and impair the behaviors of spatial recognition memory. Finally, the mechanism of adenosine triphosphate quenching by the rare-earth nanoparticles was provided to illustrate the toxicity on the mouse brain. CONCLUSIONS: This study suggested that long-term exposure of high-dose bare rare-earth nanoparticles caused an obvious damage on the spatial recognition memory in the mice.

[Homing characteristics of graft cells in leukemia mice after allogenic bone marrow transplantation with different conditioning regimens].

The aim of this study was to investigate the homing characteristics of bone marrow cells in leukemia mice after allogenic bone marrow transplantation with different conditioning regimens on the basis of a leukemia mouse model. Allogenic bone marrow transplantation was performed after three different kinds of conditioning regimen, including nonmyeloablative conditioning regimen (5 Gy (60)Co γ ray total body irradiation, A group), radiotherapeutic myeloablative conditioning regimen (9 Gy (60)Co γ ray total body irradiation, B group) and chemotherapeutic myeloablative conditioning regimen (large dose chemotherapy, C group). In the recipient mice, the nucleated cell number in peripheral blood, bone marrow and spleen was counted, the percentage of positive cells capable of connecting with FITC labeled anti-mouse H-2K(b) antibody was detected by flow cytometry and the homing ratio in bone marrow and spleen was calculated at 24, 48, 72, 96 h after bone marrow transplantation. The results showed that donor myeloid cells displayed homing and then mobilization (going out of home) in group A; homing, mobilization, and rehoming in group B and C, and there was a little delay of homing in the spleen in group C. In bone marrow, the homing efficiency of A group was the highest in early period and the lowest [(0.90 ± 0.09)%] in the fourth day with the mobilization of myeloid cells (P < 0.05), and the homing efficiency of B and C groups was lower in the early period and the highest [(2.17 ± 0.26)%, B group] in the fourth day with the rehoming of myeloid cells (P < 0.05). In spleen, the homing efficiency was similar to that in bone marrow and there still was a little delay in C group. It is concluded that the homing ratio is high in the early period and decrease obviously in 72 h after bone marrow of leukemia mice treated with nonmyeloablative conditioning regimen. The homing ratio is low in the early period and increases obviously in 72 h after bone marrow of leukemia mice treated with radio-or chemotherapeutic myeloablative conditioning regimens. The homing ratio does not obviously change between the early period and 72 h after bone marrow of leukemia mice treated with chemotherapeutic myeloablative conditioning regimen, and lies between group A and B.