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The Toxicologist - Society of Toxicology

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2051 EFFECTS OF COPPER DOPED TITANIUM DIOXIDE<br />

NANOPARTICLES IN VIVO: ROLE OF SOLUBLE METAL.<br />

B. L. Serke 1 , N. Corson 1 , P. Mercer 1 , R. Gelein 1 , M. Sahu 2 , P. Biswas 2 , G.<br />

Oberdörster 1 and A. Elder 1 . 1 Environmental Medicine, University <strong>of</strong> Rochester,<br />

Rochester, NY and 2 Energy, Environmental and Chemical Engineering, Washington<br />

University, St. Louis, St. Louis, MO.<br />

<strong>The</strong> production and use <strong>of</strong> nanoparticles (NPs; 90% fluorescent cells within 1 hr for both -45mV silica particles<br />

and carboxy- quantum dots), but confocal microscopy showed that nanoparticles<br />

were bound to the plasma membrane and not taken up by the cells. <strong>The</strong> fluorescent<br />

and flow cytometry results were similar for differentiated THP-1 cells<br />

(>90% fluorescent cells within 1 hr for both -45mV silica particles and carboxyquantum<br />

dots); however, confocal microscopy demonstrated that nanoparticles<br />

were in fact taken up by the cells. This study provides an example <strong>of</strong> a situation in<br />

which plasma membrane binding <strong>of</strong> nanoparticles did not lead to uptake (in the<br />

monocytes). Methods that do not effectively distinguish between plasma membrane<br />

bound nanoparticles and particles internalized within the cell can potentially<br />

provide misleading results regarding nanoparticle uptake. [Supported in part by the<br />

Center for NanoBio Sensors, University <strong>of</strong> Florida]<br />

2054 THE TOXIC EFFECTS OF MESOPOROUS SILICA<br />

NANOPARTICLES IN MACROPHAGES.<br />

S. Lee 1 , H. Yun 2 and S. Kim 1 . 1 Pharmacology, Kyungpook National University,<br />

Daegu, Republic <strong>of</strong> Korea and 2 Engineering Ceramics Research Group, Functional<br />

Materials Division, Korea Institute <strong>of</strong> Materials Science (KIMS), changwon, Republic<br />

<strong>of</strong> Korea.<br />

Studies on nanoparticles designed for application in biology have grown significantly<br />

over the last few decades. However, due to their small size, many nanoparticles<br />

can enter cell organelles and disrupt normal cell functions. Thus, there are general<br />

concerns regarding potential toxic effects <strong>of</strong> nanoparticles after administration.<br />

Especially, mesoporous silica (MPS) nanoparticles <strong>of</strong>fer advantage in drug delivery<br />

systems, tissue engineering, labeling and bioseparation material technologies, and<br />

transfection devices. We investigated the toxicity <strong>of</strong> MPS and underlying mechanism<br />

<strong>of</strong> actions in murine macrophages. MPS significantly lowered cytotoxicity for<br />

1 or 3 days as compared with colloidal silica nanoparticles using MTT assay. We<br />

found that apoptotic cell death was reduced on MPS treatment than colloidal silica<br />

due to reduction <strong>of</strong> p38, c-Jun N-terminal kinase (JNK), and caspase 3 activations<br />

on MPS. In addition, inflammatory response such as IL-1β, TNF-α, and IL-6 cytokines<br />

were also reduced by MPS through inhibition <strong>of</strong> NF-κB in peritoneal<br />

macrophages. <strong>The</strong>se results suggested that MPS nanoparticles has lower toxicity<br />

and inflammatory response than colloidal silica by inhibition <strong>of</strong> p38, c-Jun N-terminal<br />

kinase (JNK), caspase 3, and NF-κB.<br />

2055 ZNO NANOPARTICLE NEUROTOXICITY REQUIRES<br />

CELLULAR INFLUX OF PARTICLES.<br />

A. M. Klim 1 , B. V. Madhukar 2 and P. Cobbett 1 . 1 Pharmacology and <strong>Toxicology</strong>,<br />

Michigan State University, East Lansing, MI and 2 Pediatrics and Human<br />

Development, Michigan State University, East Lansing, MI.<br />

Recent increase in the use <strong>of</strong> nanoparticles in pharmaceutical and other industries<br />

has raised concerns <strong>of</strong> their potential impact on human health. To assess the potential<br />

neurotoxicity <strong>of</strong> engineered ZnO nanoparticles, their effect was tested on a neuroblastoma<br />

(N1E-115) cell line. Toxicity was evaluated using the MTT assay which<br />

measures activity <strong>of</strong> mitochondrial reductase enzymes and is used to measure cell<br />

viability. Initial experiments demonstrated significant cell death following cell exposure<br />

(24 hours) to ZnO nanoparticle at concentrations greater than 100nM.<br />

Similar loss <strong>of</strong> cell viability was produced following cell exposure to ZnO nanoparticles<br />

at 250nM for two hours. In later experiments, it was observed that ZnO

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