Many viruses previously have been shown to have pressurized genomes inside their viral protein shell, termed the capsid. This pressure results from the tight confinement of negatively charged viral nucleic acids inside the capsid. However, the relevance of capsid pressure to viral infection has not been demonstrated. In this work, we show that the internal DNA pressure of tens of atmospheres inside a herpesvirus capsid powers ejection of the viral genome into a host cell nucleus. To our knowledge, this provides the first demonstration of a pressure-dependent mechanism of viral genome penetration into a host nucleus, leading to infection of eukaryotic cells.
Development of reliable vectors is a major challenge in gene therapy. Previous gene transfer methods using non-viral vectors, such as liposomes or nanoparticles, have resulted in relatively low levels (35 to approximately 50%) of gene expression. We have developed a silicon nanoparticle (SNAP) system, a novel non-viral vector, for DNA transfer into cells. SNAP was synthesized chemically and modified with sodium chloride or sodium iodide. Electronmicroscopy of SNAP and fluorescence microscopy of fluorescence-labeled SNAP revealed that they were generated uniformly, had diameters of 10-100 nm, and showed a better efficiency (about 70%) of DNA transfection into cells as well as protection of DNA against degradation. The microscopy also demonstrated the adhesion of SNAP with HT1080 cell surface and entry of SNAP into the cells without cytotoxicity. Intravenous and/or intra-abdominal administration of the SNAP to mice revealed the accumulation of SNAP in the cells of the brain, liver, spleen, lung, kidney, intestine, prostate and the testis without any pathological cell changes or mortality, suggesting that they passed through the blood-brain, blood-prostate, and blood-testis barriers. These findings indicate that the SNAP generated has good biological characteristics as a potential promising vector for gene transfer, gene therapy and drug delivery.
Highly efficient catalytic reduction of CO with catecholborane has been developed by using bis(phosphinite) pincer ligated palladium thiolate complexes. Turnover frequencies up to 1780 h have been achieved at room temperature under an atmospheric pressure of CO. These thiolate complexes represent the most efficient homogeneous catalysts known to date for the reduction of CO to methanol under mild conditions.
Radiotherapy is a vitally important strategy for clinical treatment of
malignant cancers. Therefore, rational design and development of
radiosensitizers that could enhance radiotherapeutic efficacy has attracted
tremendous attention. Antiangiogenesis therapy could be a potentially effective
strategy to regulate tumor growth and metastasis due to angiogenesis plays a
pivotal role for tumor growth, invasion and metastasis to other organs. Herein,
we have rationally designed a smart and effective nanosystem by combining
ultrasmall selenium nanoparticles and bevacizumab (Avastin™,
Av), for simultaneous radiotherapy and antiangiogenic therapy of cancer. The
nanosystem was further coated with red blood cell (RBC) membranes to develop the
final construct, RBCs@Se/Av. The RBC membrane coating effectively prolongs the
blood circulation time and reduces the elimination of the nanosystem by
autoimmune responses. As expected, RBCs@Se/Av, when irradiated with X-ray
demonstrated potent anticancer and antiangiogenesis response in
vitro and in vivo, as evidenced by strong
inhibition of A375 tumor growth in nude mice, without causing any obvious
histological damage to the non-target major organs. Taken together, this study
demonstrates an effective strategy for design of smart Se-based nanosystem
decorated with RBC membrane for simultaneous cancer radiosensitization and
precise antiangiogenesis.
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