Magnetically Actuated Wormlike Nanomotors for Controlled Cargo Release

Magnetically actuated nanomotor, which swims under externally applied magnetic fields, shows great promise for controlled cargo delivery and release in biological fluids. Here, we report an on-demand release of 6-carboxyfluoresceins (FAM), a green fluorescein, from G-quadruplex DNA functionalized magnetically actuated wormlike nanomotors by applying an alternating magnetic field. This field-triggered FAM releasing process can be easily controlled by multiple parameters such as magnetic field, frequency, and exposure time. In addition, the experimental results and the theoretical simulation demonstrate that both a thermal and a nonthermal mechanism are involved in the cargo releasing process

Magnetically Actuated Wormlike Nanomotors for Controlled Cargo Release

Magnetically actuated nanomotor, which swims under externally applied magnetic fields, shows great promise for controlled cargo delivery and release in biological fluids. Here, we report an on-demand release of 6-carboxyfluoresceins (FAM), a green fluorescein, from G-quadruplex DNA functionalized magnetically actuated wormlike nanomotors by applying an alternating magnetic field. This field-triggered FAM releasing process can be easily controlled by multiple parameters such as magnetic field, frequency, and exposure time. In addition, the experimental results and the theoretical simulation demonstrate that both a thermal and a nonthermal mechanism are involved in the cargo releasing process

Magnetically Actuated Wormlike Nanomotors for Controlled Cargo Release

Magnetically actuated nanomotor, which swims under externally applied magnetic fields, shows great promise for controlled cargo delivery and release in biological fluids. Here, we report an on-demand release of 6-carboxyfluoresceins (FAM), a green fluorescein, from G-quadruplex DNA functionalized magnetically actuated wormlike nanomotors by applying an alternating magnetic field. This field-triggered FAM releasing process can be easily controlled by multiple parameters such as magnetic field, frequency, and exposure time. In addition, the experimental results and the theoretical simulation demonstrate that both a thermal and a nonthermal mechanism are involved in the cargo releasing process

Ectopic expression of miR-375 suppresses the migration of AGS cells.

<p>AGS cells transfected with miR-375 precursor (miR-375), negative control (Negative) or neither of the above (Mock) were subjected to Transwell migration assay (A) and scratch-wound healing analysis (C). (A) Representative fields of migrated cells on the underside of membrane which were fixed and stained with DAPI. (B) Total number of migrated cells on the underside of membrane was counted by IPP 6.0 software. (C) The cells migration to the wounded area was photographed by microscopy at 0 h, 12 h, 24 h and 36 h post-wounding. The dotted lines indicate the areas lacking cells. (D) The rate of migration was examined by measuring the distance of cells moved from the wound edge toward the center in 36 h after scratching. The data are presented as mean ± SE of at least three independent experiments. Bars, 50 µm. **<i>P</i><0.01.</p

Snail-Regulated MiR-375 Inhibits Migration and Invasion of Gastric Cancer Cells by Targeting JAK2

<div><p>MicroRNAs (miRNAs) have been reported to play a critical role in cancer invasion and metastasis. Our previous study showed that miR-375 frequently downregulated in gastric cancer suppresses cell proliferation by targeting Janus kinase 2 (JAK2). Here, we further found that the expression level of miR-375 is significantly decreased in metastatic gastric cancer tissues compared with the non-metastasis controls. Ectopic expression of miR-375 inhibits the migration and invasion of gastric cancer cells partially by targeting JAK2. Furthermore, miR-375 expression is negatively regulated by the metastasis associated transcription factor Snail, which directly binds to the putative promoter of miR-375. Moreover, overexpression of Snail can partially reverse the inhibition of gastric cancer cell migration caused by miR-375. Taken together, these data suggest that miR-375 may be negatively regulated by Snail and involved in gastric cancer cell migration and invasion potentially by targeting JAK2.</p></div

MiR-375 is regulated by Snail.

<p>(A) Bioinformatics analysis using the Consite program revealed potential binding sites and found that there were six binding sites of transcription factor Snail in the DNA region which containing the pri-miR-375 gene promoter. (B) The putative promoter region of the miR-375 gene was ligated upstream to the firefly luciferase reporter gene in the promoter-less pGL3-basic vector (pGL3-375pro), resulting in a 20-fold increase in the luciferase activity. (C) Luciferase activity of pGL3-375pro in cells transduced by Snail vector. Luciferase activity was efficiently repressed when pGL3-375pro vector was co-transfected with Snail expression vector. (D) The expression level of miR-375 in cells transduced by Snail overexpressing vector. Snail overexpression could reduce the expression level of miR-375 by 46%. (E) Inverse correlation between miR-375 expression and Snail mRNA level in primary gastric cancer tissues. A statistically significant correlation between miR-375 and Snail was observed by <i>Pearson's</i> method with a correlation coefficient of -0.6. **<i>P</i><0.01.</p

MiR-375 is downregulated in samples from metastasis-positive patients and cells with greater migration and invasion abilities.

<p>The expression of miR-375 was investigated by qRT-PCR. (A) Relative fold changes (Tumor tissue/Normal tissue, T/N) between gastric cancer samples from metastasis-free or –positive patients and their adjacent non-malignant tissues. The expression level of miR-375 was nearly two-fold reduction in tissues from 30 metastasis-positive patients than that from 9 metastasis-free patients, <i>*P</i><0.05. (B) The expression level of miR-375 in three human gastric epithelial cell lines with different migration and invasion abilities. The expression level of miR-375 in AGS cells was lower than that of MGC-803 and GES-1 cells. <i>**P</i><0.01. (C, D) The migration and invasion abilities of the three gastric epithelial cell lines were measured with transwell chambers. Photos are representative fields of migrated (C) or invasive (D) cells on the membrane. Bar graphs represent the average number of cells on the underside of membrane ± SE. **<i>P</i><0.01 as compared with non-malignant gastric epithelial cell line GES-1.</p

Overexpression of Snail reverses miR-375 induced inhibition of gastric cancer cells migration.

<p>The cells transfected with the indicated vectors were subjected with Transwell migration assay. (A) Representative fields of the cells on the bottom chamber at 12 h post migration were shown. Scale bars, 50 µm. (B) The average number of migrated cells from nine randomly chosen fields was counted by IPP 6.0. **<i>P</i><0.01.</p