Glutathione-ResponsiveNanoplatform for Magnetic ResonanceImaging and Chemotherapy of Pancreatic Cancer

Abstract Pancreatic ductal adenocarcinoma (PDAC) remains difficult to treat because of inefficient intracellular drug delivery and robust redox defense. Here, we developed a glutathione (GSH)-responsive biomimetic nanoplatform, termed CMnMG, for magnetic resonance (MR) imaging and gemcitabine (GEM) chemotherapy. CMnMG was prepared by loading GEM into manganese-doped mesoporous silica nanoparticles and coating them with SW1990 pancreatic-cancer-cell membranes. The membrane coating enhanced homologous tumor cell uptake and reduced macrophage internalization. After cellular uptake, GSH triggered the degradation of the manganese-containing framework, leading to GSH consumption and the release of GEM and Mn2+. This process increased intracellular drug availability and weakened antioxidant defenses. Released Mn2+ also promoted reactive oxygen species generation in the presence of endogenous H2O2, thereby enhancing the GEM-induced cytotoxicity. Meanwhile, paramagnetic Mn2+ increased the T1-weighted MR contrast. Thus, CMnMG therefore offers a GSH-responsive strategy for improving GEM chemotherapy and T1-weighted MR imaging of pancreatic cancer.