ABSTRACT
Oncolytic virotherapy is one of promising tumor therapy modalities. However, its therapeutic efficacy is still limited due to the immunogenicity and poor tumor-targeting capability. In this report, an engineered oncolytic vaccinia virus (OVV) was constructed by site-specifically introducing azide groups to the envelope of OVV during the in situ assembling process of virions. Subsequently, dibenzocyclooctynes (DBCO) derivate T7 peptide and DBCO derivate self-peptide were simultaneously conjugated to the azide-modified OVV (azide-OVV) via copper-free click chemistry. The infectivity of peptide-conjugated virus was well kept. Meanwhile, both of the targeting capacity to transferrin receptor (TfR)-overexpressed tumor cells and the in vivo blood circulation time increased. Therefore, the growth of TfR-positive tumor could be significantly inhibited after intravenously injecting the engineered OVV, while no noticeable side effects. This construction strategy can be popularized to other enveloped oncolytic virus (OV), thus a universal engineering platform can be provided for OV cancer therapy. Graphical Abstract An engineered oncolytic vaccinia virus (OVV) was constructed by bioconjugating DBCO derivate T7 peptide and DBCO derivate self-peptide with azide-modified OVV via copper-free click chemistry. As a result, the tumor inhibit effect was significantly enhanced attributed to the prolonged in vivo circulation time and improved targeting recognition capability.
Subject(s)
Collagen Type IV/chemistry , Genetic Engineering , Neoplasms/therapy , Oncolytic Viruses/genetics , Peptide Fragments/chemistry , Vaccinia virus/genetics , Animals , Azides/chemistry , Chlorocebus aethiops , Click Chemistry , Heterografts , Human Umbilical Vein Endothelial Cells , Humans , Mesenchymal Stem Cells/cytology , Mice, Inbred C57BL , Neoplasms/metabolism , Oncolytic Virotherapy , Oncolytic Viruses/immunology , Receptors, Transferrin/metabolism , Vaccinia virus/immunology , Vero CellsABSTRACT
Individual zinc oxide tetrapods were designed as multiterminal sensors by the e-beam lithography method. Different from double-terminal sensors, these sensors can give multiple responses to a single signal at the same time. The designed tetrapod devices were employed to detect light with different wavelength. The results indicate that they are remarkable optoelectronic devices, sensitive to ultraviolet light, and have advantages on distinguishing noises and increasing sensitivity. This should be helpful for weak signal measurements of nanodevices.
Subject(s)
Nanostructures/chemistry , Nanostructures/radiation effects , Nanotechnology/instrumentation , Optics and Photonics/instrumentation , Transducers , Zinc Oxide/chemistry , Zinc Oxide/radiation effects , Equipment Design , Equipment Failure Analysis , Light , Microelectrodes , Nanotechnology/methods , Reproducibility of Results , Sensitivity and SpecificityABSTRACT
ZnO nanorod close-packed arrays are successfully fabricated in a substrate-free manner by a citric acid assisted annealing process at a low growth temperature of 400 °C. Each nanorod of ZnO nanorod close-packed arrays grows along the [0001] direction and is single crystalline with an average diameter of 50 nm, and an average length of 0.5 µm. The aspect ratio is 10. The ZnO nanorod close-packed arrays show a strong exciton absorption peak at 372 nm in UV-visible absorption spectra, exhibiting a blue-shift relative to the bulk exciton absorption (387 nm). Finally, a new growth mechanism is proposed for the substrate-free preparation of ZnO nanorod close-packed arrays by a citric acid assisted annealing process.
