Development of a New Hyaluronic Acid Based Redox-Responsive Nanohydrogel for the Encapsulation of Oncolytic Viruses for Cancer Immunotherapy

Oncolytic viruses (OVs) are emerging as promising and potential anti-cancer therapeutic agents, not only able to kill cancer cells directly by selective intracellular viral replication, but also promote an immune response against tumor. Unfortunately, the bioavailability under systemic administration of OVs is limited because undesired inactivation caused host system neutralizing antibodies in bloodstream. To address this issue, a novel hyaluronic acid based redox responsive nanohydrogel was developed study delivery for OVs, with aim protect following administration. The formulated water oil (W/O) nanoemulsion method cross-linked disulfide bonds derived from thiol groups synthesized thiolated acid. One DNA OV Ad[I/PPT-E1A] one RNA Rigvir® ECHO-7 were encapsulated into nanohydrogel, respectively, view their immunovirotherapy treat cancers. nanohydrogels showed particle size approximately 300–400 nm negative zeta around ?13 mV dynamic light scattering (DLS). A uniform spherical shape observed scanning electron microscope (SEM) transmission (TEM), especially, successfully loading revealed TEM. crosslinking between chains confirmed appearance new peak assigned bond Raman spectrum. Furthermore, ability determined incubating phosphate buffered saline (PBS) pH 7.4 10 ?M or mM glutathione at 37 °C which stimulate normal physiological environment (extracellular) reductive (intracellular tumoral). relative turbidity sample real time monitored DLS indicated that could rapidly degrade within h due cleavage bonds, while maintaining stability after 5 days. Additionally, vitro cytotoxicity assays demonstrated good oncolytic activity OVs-loaded specific cell lines. Overall, results appropriate drugs, its hydrophilic porous nature, thanks capacity maintain viruses. Thus, can be considered candidate carrier immunovirotherapy.