(418) A 3D Co-Culture Model of Lipid Nanoparticle Uptake in Senescent Pancreatic Cancer

It has been shown that chemoresistance and immunosuppression in Pancreatic ductal adenocarcinoma (PDAC) can be overcome by inducing senescence to introduce therapeutic vulnerability [1]. We have shown Galectin-3 (Gal-3) overexpression in senescent PDAC cells, thus we developed Gal-3-targeting lipid nanoparticles (LNPs) encapsulating a BRD4-degrader for selective clearance. In murine PDAC models, we show that LNPs remodel the senescent tumor microenvironment (TME) resulting in improved survival. Here, we evaluate our LNP treatment on the senescent PDAC TME using 3D co-cultured “tumoroids.”