Lyotropic Liquid Crystal Precursor as an Innovative Herpes Simplex Virus Vector for Melanoma Therapy

Oncolytic virotherapy has become the frontier of biological therapy for tumor treatment in recent years, especially the Herpes Simplex Virus-1 (HSV-1) approved by the U.S. Food and Drug Administration (FDA). However, current commercial formulations using HSV-1 require strict storage conditions (-80°C) to cope with its unstable characteristics. In addition, direct injection of HSV-1 may lead to virus migration to nontumor tissues or cause unexpected immune responses representing a therapeutic risk. Herein, we developed an HSV-loaded lyotropic liquid crystal precursor (LLCP) system with in situ gelation properties as the vector for HSV-1. The prepared HSV-LLCP showed a rapid gelling property (within 2 s) and the shear viscosity ranged from 5 to 9 mPa·s, indicating its excellent drug delivery performance. Upon encapsulating in LLCP, the storage conditions were improved to -4°C within 28 days, and the HSV-1 was protected with its unique crystal lattice. The release behavior of HSV-1 LLCP showed a triphasic sustained-release pattern during the experiment period, avoiding the potential side effects. In addition, HSV-LLCP exhibited a superior oncolytic activity compared to HSV-1 solution in murine melanoma B16 cells. This study showed that HSV-LLCP would become an alternative and promising HSV-1 vector with high safety and stability for melanoma treatment in the clinic.