What features of verteporfin-lipid nanoparticles contribute to photochemical immunogenic cell death: a data driven mechanistic study

Verteporfin-liposomes have been in clinical use for over two decades. In recent years, their ability to enhance immune responses in cancer following light activation have been explored for cancer immunotherapy. The first step of enhancing immune responses in cancer is inducing immunogenic cell death. However, the exact mechanisms by which verteporfin-lipid nanoformulations can induce photochemical immunogenic cell death are poorly understood. Without this mechanistic understanding, the rational design of new verteporfin-lipid nanoformulations for improved cancer immunotherapy is not possible. In this recent work by our team, we develop a panel of verteporfin-liposomes and lipid nanoparticles with marked differences in photophysical, photochemical and biological attributes that we suspect can be important for photochemical immunogenic cell death. Using a multi-variate data-driven approach, we determine and stratify the verteporfin-lipid nanoformulation attributes that are most conducive to immunogenic cell death in pancreatic cancer cells. These insights can help pave the way for the rational design of new verteporfin-lipid nanoformulations for improved cancer immunotherapy.