Body Distribution of Inhaled FluorescentMagnetic Nanoparticles in the Mice: Jung-Taek KWON, et al. Laboratory of Toxicology, College of Veterinary Medicine, Seoul National University, Korea-Reducing the particle size of materials is an efficient and reliable tool for improving the bioavailability of a gene or drug delivery system. In fact, nanotechnology helps in overcoming the limitations of size and can change the outlook of the world regarding science. However, a potential harmful effect of nanomaterial on workers manufacturing nanoparticles is expected in the workplace and the lack of information regarding body distribution of inhaled nanoparticles may pose serious problem. In this study, we addressed this question by studying the body distribution of inhaled nanoparticles in mice using approximately 50-nm fluorescent magnetic nanoparticles (FMNPs) as a model of nanoparticles through nose-only exposure chamber system developed by our group. Scanning mobility particle sizer (SMPS) analysis revealed that the mice were exposed to FMNPs with a total particle number of 4.89 × 10 5 ± 2.37 × 10 4 /cm 3 (low concentration) and 9.34 × 10 5 ± 5.11 × 10 4 /cm 3 (high concentration) for 4 wk (4 h/d, 5 d/wk). The body distribution of FMNPs was examined by magnetic resonance imaging (MRI) and Confocal Laser Scanning Microscope (CLSM) analysis. FMNPs were distributed in various organs, including the liver, testis, spleen, lung and brain. T2-weighted spin-echo MR images showed that FMNPs could penetrate the blood-brain-barrier (BBB). Application of nanotechnologies should not produce adverse effects on human health and the Rapid Communicationenvironment. To predict and prevent the potential toxicity of nanomaterials, therefore, extensive studies should be performed under different routes of exposure with different sizes and shapes of nanomaterials. (J Occup Health 2008; 50: 1-6)
Achievement of long-term survival of patients with lung cancer treated with conventional chemotherapy is still difficult for treatment of metastatic and advanced tumors. Despite recent progress in investigational therapies, survival rates are still disappointingly low and novel adjuvant and systemic therapies are urgently needed. A recently elucidated secretory pathway is attracting considerable interest as a promising anticancer target. The cis-Golgi matrix protein, GOLGA2/GM130, plays an important role in glycosylation and transport of protein in the secretory pathway. In this study, the effects of short hairpin RNA (shRNA) constructs targeting GOLGA2/GM130 (shGOLGA2) on autophagy and lung cancer growth were evaluated in vitro and in vivo. Downregulation of GOLGA2/GM130 led to induction of autophagy and inhibition of glycosylation in A549 cells and in the lungs of K-ras(LA1) mice. Furthermore, downregulation of GOLGA2/GM130 decreased angiogenesis and cancer cell invasion in vitro and suppressed tumorigenesis in lung cancer mice model. The tumor specificity of sequence targeting GOLGA2/GM130 was also demonstrated. Taken together, these results suggest that induction of autophagy by shGOLGA2 may induce cell death rather than cell survival. Therefore, downregulation of GOLGA2/GM130 may be a potential therapeutic option for lung cancer.
Carbon nanotubes (CNT) are known to have widespread industrial applications; however, several reports indicated that these compounds may be associated with adverse effects in humans. In this study, multiwalled carbon nanotubes were administered to murine lungs intratracheally to determine whether acute and chronic pulmonary toxicity occurred. In particular, pristine multiwalled carbon nanotubes (PMWCNT) and acid-treated multiwalled carbon nanotubes (TMWCNT) were used in this study. In broncheoalveolar lavage fluid (BALF) cell analysis, PMWCNT induced more severe acute inflammatory cell recruitment than TMWCNT. Histopathologically, both PMWCNT and TMWCNT induced multifocal inflammatory granulomas in a dose-dependent manner. The observed granulomas were reversible, with TMWCNT-induced granulomas diminishing faster than PMWCNT-induced granulomas. Although the area of granuloma reduced with time, hyperplasia and dysplastic characteristics such as mitotic figures, anisokaryosis, and anisocytosis were still observed. These findings demonstrate that MWCNT induces granulomatous inflammation, and the duration and pattern of inflammation seem to vary depending upon the types of MWCNT to which mice are exposed. Therefore, toxicity studies on various types of CNT are needed as the responsiveness to these compounds differs.
Immunoassays using nanomaterials have been rapidly developed for the analysis of multiple biomolecules. Highly sensitive and biocompatible surface enhanced Raman spectroscopy-active nanomaterials have been used for biomolecule analysis by many research groups in order to overcome intrinsic problems of conventional immunoassays. We used fluorescent surface-enhanced Raman spectroscopic dots (F-SERS dots) to detect biomolecules in this study. The F-SERS dots are composed of silver nanoparticle-embedded silica nanospheres, organic Raman tagging materials, and fluorescent dyes. The F-SERS dots demonstrated highly sensitive, selective, and multifunctional characteristics for multiplex targeting, tracking, and imaging of cellular and molecular events in the living organism. We successfully applied F-SERS dots for the detection of three cellular proteins, including CD34, Sca-1, and SP-C. These proteins are simultaneously expressed in bronchioalveolar stem cells (BASCs) in the murine lung. We analyzed the relative expression ratios of each protein in BASCs since external standards were used to evaluate SERS intensity in tissue. Quantitative comparisons of multiple protein expression in tissue were first attempted using SERS-encoded nanoprobes. Our results suggested that immunoassays using F-SERS dots offered significant increases in sensitivity and selectivity. Such immunoassays may serve as the primary next-generation labeling technologies for the simultaneous analysis of multiple biomolecules.
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