Folate-modified liposomes for co-delivery of schisandrin A and oxaliplatin to enhance colorectal cancer cell death.

The incidence of colorectal cancer (CRC) poses a significant threat to human life. Immunotherapy has emerged as an efficacious treatment against CRC. However, it is hindered by the challenge of inadequate immunogenicity. In addition to exerting inhibitory effects on cancer cell activity, the chemotherapeutic agent oxaliplatin (OXP) possesses the advantage of inducing immunogenic cell death (ICD) through reactive oxygen species (ROS). Schisandrin A (SCHA) can augment ROS production stimulated by OXP in cancer cells and enhance the efficacy of ICD. Consequently, we developed a liposome formulation named FOS-lip that co-delivers SCHA and OXP to actively target CRC cells. The FOS-lip exhibited appropriate particle size, high drug loading capacity, and less than 5% hemolysis. Due to the pH sensitivity, both drugs were rapidly released under acidic conditions, providing a foundation for their therapeutic action. Furthermore, liposomes modified with active targeting moieties facilitated efficient internalization of drugs into cells. Through liposomal delivery, these two drugs synergistically inhibited tumor cells (CI < 1). FOS-lip significantly elevated ROS levels in tumor cells and importantly promoted the induction of ICD, leading to release/exposure of damage-associated molecular patterns (DAMPs) and enhanced dendritic cell maturation. Therefore, this study presents a strategy to enhance the immunogenicity of CRC by addressing the issue of insufficient OXP-induced ICD and offers valuable insights for future research.