Application of virus targeting nano-carrier drug delivery system in virus-induced central nervous system diseases treatment.

Virus-induced central nervous system (CNS) diseases represent a significant burden to animal health worldwide. The difficulty in treating these diseases is mainly attributable to the elaborate barrier system, which limits the transport of drugs to the infected sites. Therefore, it is necessary to develop smart delivery technologies for these diseases treatment. In the study, viral nervous necrosis disease was studied as a model to evaluate the feasibility of multi-walled carbon nanotubes (MWCNTs) conjugated with virus-specific nanobody and antiviral drug for targeted therapy of virus-induced CNS diseases. The virus (named as PGNNV) was isolated, identified and purified from diseased grouper. A naïve phage-displayed alpaca nanobody library was constructed, and the purified PGNNV was used for biopanning of PGNNV-specific nanobody from the library. The targeted delivery system based on MWCNTs conjugated with polyethylenimine, ribavirin and PGNNV-specific nanobody was constructed, designated as MWCNTs-PEI-R-Nb. Targeting ability and treatment effects of the MWCNTs-PEI-R-Nb were checked both in vitro and in vivo. MWCNTs-PEI-R-Nb showed an increasing distribution in PGNNV-infected cells, and an obvious accumulation in the brain of PGNNV-infected zebrafish larvae. MWCNTs-PEI-R-Nb also showed a strong anti-PGNNV ability both in vitro and in vivo. The mortality of larvae treated with MWCNTs-PEI-R-Nb (equivalent to 100 mg/L ribavirin) was 27% during 10 days post infection, while that was 100% for the control group. The results so far indicated that MWCNTs conjugated with antiviral drugs and viral-specific antibody are effective means for virus-induced CNS diseases targeted therapy.