14 research outputs found

    Investigation of Thermally Induced Cellular Ablation and Heat Response Triggered by Planar MoS<sub>2</sub>‑Based Nanocomposite

    No full text
    In comparison to conventional tumor treatment methods, photothermal therapy (PTT) is one of the innovative therapeutic strategies that employs light to produce localized heat for targeted ablation of cancer cells. Among the various kinds of heat generation nanomaterials, transition metal dichalcogenide nanosheets, especially molybdenum disulfide (MoS<sub>2</sub>), have recently been investigated as one of the promising PTT candidates because of their strong absorbance in the near-infrared (NIR) tissue transparency window and excellent photothermal conversion capability. In line with the great potential of MoS<sub>2</sub>-based nanomaterials in biomedical applications, their intrinsic therapeutic performance and corresponding cellular response are required to be continually investigated. In order to further improve MoS<sub>2</sub>-based PTT efficacy and dissect the molecular mechanism during heat stimuli, in this study, we successfully designed a novel and effective PTT platform by integration of MoS<sub>2</sub> nanosheets with peptide-based inhibition molecules to block the function of heat shock proteins (Hsp90), one type of chaperone proteins that play protective roles in living systems against cellular photothermal response. Such a combined nanosystem could effectively induce cell ablation and viability assays indicated approximately 5-fold higher PTT treatment efficacy (8.8% viability) than that of MoS<sub>2</sub> itself (48% viability) upon 808 nm light irradiation. Moreover, different from the case based on MoS<sub>2</sub> alone that could cause tumor ablation through the process of necrosis, the detailed mechanism analysis revealed that the inhibition of Hsp90 could significantly increase the photothermally mediated apoptosis, hence resulting in remarkable enhancement of photothermal treatment. Such promising studies provide the great opportunity to better understand the cellular basis of light-triggered thermal response. Moreover, they can also facilitate the rational design of new generations of PTT platforms toward future theranostics

    Human Transport Protein Carrier for Controlled Photoactivation of Antitumor Prodrug and Real-Time Intracellular Tumor Imaging

    No full text
    Current anticancer chemotherapy often suffers from poor tumor selectivity and serious drug resistance. Proper vectors for targeted delivery and controlled drug release play crucial roles in improving the therapeutic selectivity to tumor areas and also overcoming the resistance of cancer cells. In this work, we developed a novel human serum albumin (HSA) protein-based nanocarrier system, which combines the photoactivatable Pt­(IV) antitumor prodrug for realizing the controlled release and fluorescent light-up probe for evaluations of drug action and efficacy. The constructed Pt­(IV)-probe@HSA platform can be locally activated by light irradiation to release the active Pt species, which results in enhanced cell death at both drug-sensitive A2780 and cisplatin-resistant A2780cis cell lines when compared to the free prodrug molecules. Simultaneously, the cytotoxicity caused by light controlled drug release would further lead to the cellular apoptosis and trigger the activation of caspases 3, one crucial protease enzyme in apoptotic process, which could cleave the recognition peptide moiety (DEVD) with a flanking fluorescent resonance energy transfer (FRET) pair containing near-infrared (NIR) fluorophore Cy5 and quencher Qsy21 on the HSA nanocarrier surface. The turn-on fluorescence in response to caspase-3 could be assessed by fluorescence microscopy and flow cytometry analysis. Our results supported the hypothesis that such a unique design may present a successful platform for multiple roles: (i) a biocompatible protein-based nanocarrier for drug delivery, (ii) the controlled drug release with strengthened therapeutic effects, (iii) real-time monitoring of antitumor drug efficacy at the earlier stage

    Non-metric multidimensional scaling (NMDS) plots of bacterial communities based on taxonomic dissimilarity (a) and betaMNTD (b) matrix, respectively.

    No full text
    <p>The stress value reflects how well the ordination summarizes the observed distances among samples (lower than 20% can be ecologically interpretable and useful). Soil variables were fitted as vectors onto each ordination plot, and significant vectors at 95% confidence level (<i>P</i> ≤ 0.05) were displayed.</p

    Partial correlation between environmental heterogeneity (environmental distance) and taxonomic dissimilarity (a); and betaMNTD (b); and betaNTI (c).

    No full text
    <p>Residuals of the x and y variables are plotted in order to account for the effects of vertical distance and spatial autocorrelation. Solid lines represent linear regressions and the significance levels are determined by partail Mantel tests (9999 permutations).</p

    ASC regulates DCs antigen processing events <i>in vitro</i> and i<i>n vivo</i>.

    No full text
    <p>WT and ASC<sup>-/-</sup> DCs were γ-irradiated and stimulated with UV-inactivated <i>C</i>. <i>muridarum</i> and then co-cultured with splenic T cells from immune animals. A). T cell proliferation was determined using Cell Signaling XTT Cell Viability Kit protocol. Results are expressed as cell viability ratio, which is the ratio between the absorbance values of stimulated and non-stimulated cells and the bars represent the mean and SD of three independent experiments. B). The supernatants were collected and cytokines amounts determined using a 23 plex multiplex assay from Bio-Rad. The concentration of the cytokines for each sample was obtained by extrapolation from a standard calibration curve generated simultaneously. Data was calculated as the mean and SD for triplicate cultures in each experiment. The results were from 2 independent experiments and are reported as mean cytokine concentrations (pg/ml) ± SD. Results were compared using Student’s t-test. *, P<0.05. C). Isolated DCs from WT and ASC<sup>-/-</sup> mice were stimulated with <i>C</i>. <i>muridarum</i> and adoptively transferred into naïve WT mice. Mice were then infected intravaginally with live <i>C</i>. <i>muridarum</i> one week after the adoptive transfer. Infection was monitored by periodic cervicovaginal swabbing every 3 days for 2 weeks and then once every week. The <i>C</i>. <i>muridarum</i> IFUs was determined using standard methods with anti-chlamydial antibodies from Bio-Rad. The experiment was repeated three times.</p
    corecore