(216) Enhancing PARP inhibitors efficacy in BRCA1-deficient tumors with radiation-guided nanoparticles

Introduction: Poly (ADP-ribose) polymerase inhibitors (PARPi) have transformed BRCA1-mutated breast (BC) and ovarian cancer (OC) treatment, but their efficacy is short-lived [1]. BRCA1-deficient tumors express high levels of PD-L1 [2], further increased by PARPi treatment, suggesting potential for combining PARPi with immune checkpoint inhibitors. To address challenges with drug properties and pre-clinical models, we developed P-selectin-targeted PLGA-PEG-(SO3)2 nanoparticles (NPs) co-encapsulating niraparib and a small molecule of PD-L1 inhibitor (PD-L1i), and evaluated on unique 3D cancer-on-a-chip model.