Co-delivery of gemcitabine and Triapine by calcium carbonate nanoparticles against chemoresistant pancreatic cancer

Abstract

Pancreatic cancer is a malignant disease with high mortality, and its systemic treatment strategy mainly focuses on chemotherapy. Yet, the overall prognosis of pancreatic cancer patients is still extremely poor with a low survival rate. Gemcitabine (GEM) is a widely used chemotherapeutic agent for the treatment of pancreatic cancer. However, GEM chemoresistance remains the major challenge. In this study, we prepared calcium carbonate nanoparticles (CaCO₃ NPs) loaded with a nucleotide reductase inhibitor (Triapine) and GEM to suppress the GEM resistance of pancreatic cancer cells (PANC-1/GEM) and solve the problem of poor solubility of Triapine. CaCO₃-GEM-Triapine NPs nano-formulations enhanced the therapeutic effect of GEM-based chemotherapy by inhibiting cancer cell proliferation, migration, and resistance to GEM using both 2D PANC-1/GEM cells and 3D tumor spheroids. The study indicated that CaCO₃ NPs loaded with GEM and Triapine could provide an effective treatment option to overcome drug resistance in pancreatic cancer.

Keywords: Calcium carbonate nanoparticles; Drug resistance; Gemcitabine; Pancreatic cancer; Triapine.