Search

Despite the effectiveness of classic treatments and available diagnostic tools, cancer continues to be a leading world health problem, with devastating cancer-related death rates. Advances in oncolytic virotherapy have shown promise as potentially effective treatment options in the fight against cancer. The poxviruses have many features that make them an attractive platform for the development of oncolytic vectors, with some candidates currently in clinical trials. Here, we report the design and generation of a new oncolytic vector based on the vaccinia virus Western Reserve (WR) strain. We show that the WR-Δ4 virus, with the combined deletion of four specific viral genes that act on metabolic, proliferation, and signaling pathways (A48R, B18R, C11R, and J2R), has effective anti-tumor capabilities in vivo. In WR-Δ4-infected mice, we observed strong viral attenuation, reduced virus dissemination, and efficient tumor cell growth control in the B16F10 syngeneic melanoma model, with enhanced neutrophil migration and activation of tumor antigen-specific immune responses. This approach provides an alternative strategy toward ongoing efforts to develop an optimal oncolytic poxvirus vector. Keywords: oncolytic vectors, vaccinia virus, virotherapy, immune responses

Viral templates are highly versatile biotemplates used for the synthesis of nanostructured materials. Rotavirus VP6 self-assembles into nanotubular hollow structures with well-defined diameters and variable lengths, serving as a nucleic acid-free biotemplate to synthesize metal nanoparticles of controlled size, shape, and orientation. Molecular docking simulations show that exposed residues (H173-S240-D242 and N200-N310) of VP6 have the ability to specifically bind Pd(II) ions, which serve as nucleation sites for the growth and stabilization of palladium nanoclusters. Using VP6 nanotubes as biotemplates allows for obtaining small Pd particles of 1–5 nm in diameter. Advanced electron microscopy imaging and characterization through ultra-high-resolution field-emission scanning electron microscopy (UHR-FE-SEM) and spherical aberration-corrected scanning transmission electron microscopy (Cs-STEM) at a low voltage dose (80 kV) reveals, with high spatial resolution, the structure of Pd nanoparticles attached to the macromolecular biotemplates.

New technologies require the development of novel nanomaterials that need to be fully characterized to achieve their potential. High-resolution low-voltage scanning transmission electron microscopy (STEM) has proven to be a very powerful technique in nanotechnology, but its use for the characterization of nanobiomaterials has been limited. Rotavirus VP6 self-assembles into nanotubular assemblies that possess an intrinsic affinity for Au ions. This property was exploited to produce hybrid nanobiomaterials by the in situ functionalization of recombinant VP6 nanotubes with gold nanoparticles. In this work, Raman spectroscopy and advanced analytical electron microscopy imaging with spherical aberration-corrected (Cs) STEM and nanodiffraction at low-voltage doses were employed to characterize nanobiomaterials. STEM imaging revealed the precise structure and arrangement of the protein templates, as well as the nanostructure and atomic arrangement of gold nanoparticles with high spatial sub-Angstrom resolution and avoided radiation damage. The imaging was coupled with backscattered electron imaging, ultra-high resolution scanning electron microscopy and x-ray spectroscopy. The hybrid nanobiomaterials that were obtained showed unique properties as bioelectronic conductive devices and showed enhanced Raman scattering by their precise arrangement into superlattices, displaying the utility of viral assemblies as functional integrative self-assembled nanomaterials for novel applications. [ABSTRACT FROM AUTHOR]