Cytotoxic effects of upconversion nanoparticles in primary hippocampal cultures

Vedunova, Maria; Mishchenko, Tatiana A.; Митрошина, Е.В.; Ponomareva, Natalia; Yudintsev, Andrey; Generalova, Alla N.; Deyev, Sergey M.; Мухина, И.В.; Semyanov, Alexey; Zvyagin, Andrei V.

doi:10.1039/c6ra01272h

Cited by 20 publications

(23 citation statements)

References 41 publications

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“…Although ligand-free lanthanide-doped nanoparticles are known to induce a decreased cell viability due to intracellular ATP deprivation in the live cells, little study is reported to investigate the neurotoxicity effects of the bare nanoparticles in vitro . [ 8 9 ] However, almost these studies used silica-coated rare-earth nanoparticles to study their biological toxicity in a short-term period. This could not reveal their toxicity in the practical applications.…”

Section: Discussionmentioning

confidence: 99%

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

Lin

Liu

Chen

et al. 2017

Chinese Medical Journal

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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.

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Section: Discussionmentioning

confidence: 99%

“…[ 8 ] Furthermore, Vedunova et al . [ 9 ] found that bare rare-earth nanoparticles are toxic to hippocampal cells in vitro . It is well known that ATP is the most important neurotransmitter in the mouse brain.…”

Section: Introductionmentioning

confidence: 99%

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

Lin

Liu

Chen

et al. 2017

Chinese Medical Journal

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“…[ 16 ] In addition, Maria et al . [ 17 ] found that bare rare-earth nanoparticles (RENPs) are toxic to hippocampal cells in vitro . So far, most reported studies have focused on the in vitro toxicity assays; however, the fate of RENPs circulating in the blood vessels and tissues in vivo is much more complicated.…”

Section: Introductionmentioning

confidence: 99%

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

Chen

Shi²,

Liu

et al. 2018

Chinese Medical Journal

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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.

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“…However, despite a wide range of existing nanomaterials, few of them meet the above criteria. Recent studies reveled that some types of NPs provide cytotoxic effects to the human organism, especially to the nervous system [5]. Therefore, it is so important to evaluate biosafety of the emerging NPs for brain cells and tissues.…”

Section: Introductionmentioning

confidence: 99%

Biocompatibility of Bare Nanoparticles Based on Silicon and Gold for Nervous Cells

Mishchenko¹,

Lewkina²,

Shishkina³

et al. 2018

KEn

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This work aimed to investigate the biocompatibility of bare (ligand-free) lasersynthesized nanoparticles (NPs) based on silicon (Si) and gold (Au) with primary hippocampal cultures. 1%, 5% and 7% of culture medium were replaced by 0.1 mg/mL NP solution on day 14 of culture development in vitro. Our studies revealed that the NPs caused a dose-dependent cytotoxic effect, which was manifested by an increase the number of dead cells and a decrease of the spontaneous functional calcium activity of neural networks. Au NPs revealed less pronounced cytotoxic effect than Si ones and it can be explained by larger size and better solubility of Si NPs.

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Cytotoxic effects of upconversion nanoparticles in primary hippocampal cultures

Abstract: The research demonstrated that upconversion nanoparticles (UCNPs) are toxic to nervous cells. The cytotoxic severity depends on surface modification of UCNPs.

Cited by 20 publications

References 41 publications

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

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

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

Biocompatibility of Bare Nanoparticles Based on Silicon and Gold for Nervous Cells

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