Scheme 1.

Schematic illustration of the preparation and tumor targeting principle of the galactose-polyethylene glycol polymer chain modified oHSV (glycosylated-PEG-oHSV), and the modulation of the tumor microenvironment by glycosylated-PEG-oHSV to enhance antitumor immunity. The resulting glycosylated-PEG-oHSV exhibited targeted delivery to tumors and increased cell infection, while also reducing infection of healthy cells. Upon systemic administration, the glycosylated-PEG-oHSV effectively and specifically destroyed HCC tumors, stimulated the immune responses, and reshaped the immunosuppressive tumor microenvironment by decreasing Tregs and increasing infiltration of IFN-γ⁺CD8⁺T cells, CD8⁺T cells, and NK cells within tumors, which led to efficient inhibition of HCC tumor growth.