Browsing by Author "Hong, Meng-Yeng"

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Control of In Vivo Transport and Toxicity of Nanoparticles by Tea Melanin
(2012)
Chen, Yu-Shiun
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Hung, Yao-Ching
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Hong, Meng-Yeng
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Onischuk, Andrei Aleksandrovich
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Chiou, Jin Chern
"Nanoparticles are unfamiliar to researchers in toxicology. Toxicity may be generated simply due to the reduction in size. Compounds that prevent or cure toxic materials may not work on nanoparticles. Furthermore, as there are more and more applications of nanoparticles in drug delivery and in vivo imaging, controlling the transport and toxicity will be primary concerns for medical application of nanoparticles. Gold nanoparticles (GNPs) if injected intraperitoneally into mice can enter hippocampus and induce cognitive impairment. GNPs caused a global imbalance of monoamine levels, specifically affecting the dopaminergic and serotonergic neurons. Pretreatment of tea melanin significantly prevented the deposition of GNPs in mouse brains, especially in the hippocampus. Pretreatment of melanin completely alleviated GNP-induced impairment of cognition. Pre-administration of melanin stably maintained monoamines at normal profiles. Melanin completely prevented the invasion of GNPs into the Cornu Ammonis region of the hippocampus shown by coherent anti-Stoke Raman scattering microscopy. Here we show that the administration of tea melanin prevented the accumulation of Au in brain, the imbalance of monoamines, and the impairment of cognition in mice. The current study provides a therapeutic approach to toxicity of nanoparticles and a novel strategy to control the transport of GNP in mouse brain."
Gold nanoparticles caused learning impairment in mice
(2009)
Chen, Yu-Shiun
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Hung, Yao-Ching
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Liau, Ian
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Lin, Li-Wei
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Hong, Meng-Yeng
Aims : To investigate the toxic effect of gold nanoparticles (GNPs) to the learning and memory of mice. Main methods: Naked GNPs of 17 nm and 37 nm were synthesized, purified, and injected intraperitoneally into BALB/C mice at a dose of 8 mg/kg/week. Passive avoidance test was performed to detect the possible leaning impairment. Biochemical analysis to examine levels of monoamine and acetylcholine in mouse brain was also performed. ICP-MS was performed to examine the presence of GNP in brain. Localization of GNP at hippocampus was surveyed by ex vivo Coherent anti-Stoke Raman scattering (CARS) microscopy. Transmission electron microscopy (TEM) was also performed to verify the cellular location of GNPs at hippocampus. Key findings: Both 17 nm and 37 nm GNPs induced severe sickness in rnice. However, only 17 rim GNP impaired the learning and memory of mice. GNP treatment elevated levels of dopamine from 114.5 ng/mouse brain to 143.6 ng/mouse brain for 17 nm (p<0.01) and to 138.2 for 37 nm GNP (p<0.05). Serotinin was significantly reduced by 17 nm GNP treatment from 57.2 ng/mouse brain to 44.3 ng/mouse brain (p<0.05). ICP-MS indicated the presence of GNPs in every part of the brain. CARS microscopy showed that 17 nm GNP was located at the Cornu Amonis regions of hippocampus where neuronal cells clustered, while 37 nm GNP was excluded from the cell clustered region. TEM and EDAX verified the presence of 17 nm GNP in the cytoplasm and in the dendrite of pyramidal cell, while 37 rim GNP was found in the extracellular region of neuronal cells. TEM image also indicated that both endocytosis and free diffusion coexisted for the invasion of 17 nm GNP. Significance: The current study provided evidence that nanoparticles were capable of entering into brain and affecting normal brain function. The size-dependent invading ability of GNPs provides an extra dimension for drug delivery.
Size-dependent impairment of cognition in mice caused by the injection of gold nanoparticles
(2010-12-03)
Chen, Yu-Shiun
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Hung, Yao-Ching
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Lin, Li-Wei
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Liau, Ian
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Hong, Meng-Yeng
We explored the size-dependent impairment of cognition in mice caused by the injection of gold nanoparticles (GNPs). GNPs of 17 and 37 nm in diameter were injected intraperitoneally into BALB/c mice at doses ranging from 0.5 to 14.6 mg kg(-1). ICP-MS was performed on brain tissue collected 1, 14 and 21 days after the injection. A passive-avoidance test was performed on day 21. Monoamine levels were determined on day 21. The microscopic distribution of GNPs in the hippocampus was examined using coherent anti-Stokes Raman scattering (CARS) microscopy and transmission electron microscopy (TEM). The results indicated that 17 nm GNPs passed through the blood-brain barrier more rapidly than 37 nm GNPs. Treatment with 17 nm GNPs decreased the latency time, which was comparable to the effect of scopolamine treatment, while 37 nm GNPs showed no significant effect. Dopamine levels and serotonin levels in the brain were significantly altered by the injection of 17 and 37 nm GNPs. GNPs affected dopaminergic and serotonergic neurons. CARS microscopy indicated that 17 nm GNPs entered the Cornu Ammonis (CA) region of the hippocampus, while 37 nm GNPs were excluded from the CA region. TEM verified the presence of 17 nm GNPs in the cytoplasm of pyramidal cells. In this study, we showed that the ability of GNPs to damage cognition in mice was size-dependent and associated with the ability of the particles to invade the hippocampus. The dosage and duration of the treatment should be taken into account if GNPs are used in the future as vehicles to carry therapeutic agents into the brain.