Nanoscale Melittin@Zeolitic Imidazolate Frameworks for Enhanced Anticancer Activity and Mechanism Analysis

The cytolytic peptide melittin (MLT) is an important candidate of anticancer drug owing to its hemolytic properties. Nevertheless, its clinical applications are severely restricted as a result of its nonspecific toxicities like hemolysis. In this work, we reported MLT-loaded zeolitic imidazolate framework-8 (MLT@ZIF-8) nanoparticles (NPs). The formed MLT@ZIF-8 NPs not only possess excellent stability but also efficiently inhibit the hemolysis bioactivity of MLT. Confocal scanning imaging and cytotoxicity experiments revealed that as-synthesized MLT@ZIF-8 NPs exhibit enhanced cellular uptake and cytotoxicity toward cancer cells compared to MLT. The mechanism is well investigated by a series of transcriptome analysis, which indicates that MLT@ZIF-8 NPs can regulate the expression of 3383 genes, and the PI3K/Akt-regulated p53 pathway is involved in MLT@ZIF-8 NPs induced A549 cells apoptosis. Finally, MLT@ZIF-8 NPs exhibit enhanced antitumor activity than free MLT <i>in vivo</i>, while no obvious systemic toxicity has been found. This work emphasizes the great potential of utilizing MOF as a simple and efficient nanoplatform for deliverying cytolytic peptides in cancer treatment, and also the investigation on the antitumor mechanism could provide theoretical support for clinical usage of MLT

Melanoma stem cell vaccine induces effective tumor immunity against melanoma

Melanoma stem cells (MSCs)-based vaccine strategies have been a potent immunotherapeutic approach for melanoma treatment, which aimed at inducing specific anti-tumor immunity and targeting cancer stem-like cells. As the main cancer-fighting immune cells, CD8+T cells play an important role in vaccine-induced antitumor immunity. Here, we developed a novel MSC vaccine that induces CD8+T cells to target melanoma stem cells specifically. The MSC vaccine was prepared for our study in order to determine the effectiveness of antitumor immunity. The proportion and activity of CD8+T cells were examined in the spleen after immunization, in particular, the expression and cytotoxicity of the immune checkpoint of spleen lymphocytes were detected by flow cytometry and ELISA, moreover, tumor size and the number of lung metastasis nodules were observed and the specific killing effect of the vaccine was evaluated in immunized mice. We found that the MSC vaccine could promote DCs maturation, activate CD8+T cells, suppress the expression of CTLA-4, PD-1, and Tim-3, and increase the expression of IFN-γ and GzmB of CD8+T cells. Melanoma growth and metastasis were inhibited by the vaccine’s specific targeted killing effect. The vaccines based on melanoma stem cells (MSCs) delay the progression of melanoma by inducing anti-tumor immune responses in CD8+T cells.</p

Rapid deployment of a mobile biosafety level-3 laboratory in Sierra Leone during the 2014 Ebola virus epidemic

<div><p>Background</p><p>Ebola virus emerged in West Africa in December 2013. The high population mobility and poor public health infrastructure in this region led to the development of the largest Ebola virus disease (EVD) outbreak to date.</p><p>Methodology/Principal findings</p><p>On September 26, 2014, China dispatched a Mobile Biosafety Level-3 Laboratory (MBSL-3 Lab) and a well-trained diagnostic team to Sierra Leone to assist in EVD diagnosis using quantitative real-time PCR, which allowed the diagnosis of suspected EVD cases in less than 4 hours from the time of sample receiving. This laboratory was composed of three container vehicles equipped with advanced ventilation system, communication system, electricity and gas supply system. We strictly applied multiple safety precautions to reduce exposure risks. Personnel, materials, water and air flow management were the key elements of the biosafety measures in the MBSL-3 Lab. Air samples were regularly collected from the MBSL-3 Lab, but no evidence of Ebola virus infectious aerosols was detected. Potentially contaminated objects were also tested by collecting swabs. On one occasion, a pipette tested positive for EVD. A total of 1,635 suspected EVD cases (824 positive [50.4%]) were tested from September 28 to November 11, 2014, and no member of the diagnostic team was infected with Ebola virus or other pathogens, including Lassa fever. The specimens tested included blood (69.2%) and oral swabs (30.8%) with positivity rates of 54.2% and 41.9%, respectively. The China mobile laboratory was thus instrumental in the EVD outbreak response by providing timely and reliable diagnostics.</p><p>Conclusions/Significance</p><p>The MBSL-3 Lab significantly contributed to establishing a suitable laboratory response capacity during the emergence of EVD in Sierra Leone.</p></div

Overview of the China mobile laboratory diagnostic team’s composition and their tasks.

<p>Overview of the China mobile laboratory diagnostic team’s composition and their tasks.</p

Schematic diagram of the “Four Flows”.

<p>Personnel, materials, water and air flow management were the key elements of biosafety measures in the MBSL-3 Lab.</p

Samples and test results from September 28 to November 11, 2014.

<p>Samples and test results from September 28 to November 11, 2014.</p

Worksite layout for the China mobile laboratory diagnostic team.

<p>Worksite layout for the China mobile laboratory diagnostic team.</p

Layout of the mobile biosafety level-3 laboratory.

<p>The main and auxiliary containers were connected by an airtight soft connection and together formed a complete biosafety level-3 (BSL-3) lab. The instruments represented by letters were listed in <a href="http://www.plosntds.org/article/info:doi/10.1371/journal.pntd.0005622#pntd.0005622.s003" target="_blank">S1 Table</a>.</p

Diagnostic algorithm for laboratory testing.

<p>Diagnostic algorithm for laboratory testing.</p

Mobile biosafety level-3 laboratory at its mission in Sierra Leone.

<p>(A) Exterior of the mobile biosafety level-3 laboratory. (B) View to the biosafety level-3 laboratory. Two different perspectives (B1 and B2) were shown. (C) View to the auxiliary container. C1) Pass box (left) and expanded-metal door (middle). C2) Monitoring unit and table for experimental preparation. C3) Shower cubicle. C4) Waste treatment room. (D) View to the command container. D1) Room for meeting or for watching monitoring videos. D2) “King View” industry control software. D3) Real-time surveillance video.</p