Efficient antiviral co-delivery using polymersomes by controlling the surface density of cell-targeting groups for influenza A virus treatment

Influenza A virus (IAV), which causes one of the most contagious diseases, is a global health concern and is responsible for seasonal epidemics and pandemics. Despite notable efforts towards developing antiviral agents and drugs, a vast majority of these, especially intracellular drugs, have shown limited efficacy due to non-specificity and low viability under physiological or endosomal conditions. Polymersomes consist of phenylboronic acid (PBA) pendant group polymers (PBASomes) and can act as drug carriers; they have sialic acid-targeting properties and can gain greater access to the intracellular space for the transport of antivirals within the host cell. Amphiphilic copolymers comprising methoxy-poly(ethylene glycol)-block-poly(phenylalanine) (mPEG-b-pPhe) formed polymersomes, which encapsulated mir-323a in the core and favipiravir in the exterior layer as hydrophilic and hydrophobic antivirals, respectively. For maximizing the cellular uptake of PBASomes via receptor-mediated endocytosis, the surface density of PBA was controlled with PBA-functionalized copolymers (PBA-PEG-pPhe). Combination therapy by employing polymersomes with PBA functional groups induced a synergistic effect against H1N1 virus infection in vitro. We believe that antiviral co-delivery using these polymersomes would provide better opportunities to improve transfection of therapeutic substances for IAV treatment.