Folate Receptor-mediated Herpes Simplex Virus Re-targeting

Herpes Simplex Virus I (HSV-1) is a very promising oncolytic virus for cancer biotherapeutics. However, viral tropism is one of the major problems hindering the development of HSV-1 as a anticancer agent. To overcome that, folate conjugated poly(ethylene glycol) (FA-PEG) was immobilized on the surface of HSV-1, and its biological properties were evaluated. PEGylated HSV-1 had higher zeta potential value than unmodified virus, suggesting that PEGylation had increased colloidal stability of HSV-1. FA-PEG-HSV exhibited greatly enhanced targeting specificity for folate receptor overexpressed tumor cells in vitro. In addition, PEGylated HSV elicited lesser extent of IL-6 released from macrophage cells. In vivo anti-tumor studies demonstrated that FA-PEG-HSV had higher anti-tumor efficiency than naked HSV. Furthermore, lower concentration of FA-PEG-HSV was detected in normal tissues than unmodified HSV. These results indicate that FA-PEG-HSV is a successful folate receptor-targeted oncolytic virus.