A pH-Responsive MnCO3 Nanoplatform with MRI/NIR Imaging Guidance for Chemo-Photothermal-Photodynamic Synergy of Pancreatic Cancer

Accurate diagnosis and effective treatment of pancreatic cancer are essential to improving survival rates, yet current strategies are highly limited by toxicity of therapeutic drugs and efficacy challenges. Herein, we proposed a biodegradable nanosystem (denoted as MnCO3–BSA@DOX/IR820) based on manganese carbonate (MnCO3) loaded with doxorubicin (DOX) and photothermal agent IR820. This platform integrates chemotherapy with photothermal/photodynamic therapy (PTT/PDT) under 808 nm laser irradiation, achieving synergistic antitumor efficacy against pancreatic cancer. Specifically, the MnCO3-based nanosystem can enhance tumor accumulation, while the hydrogen peroxide (H2O2)-enriched acidic tumor microenvironment (TME) triggers oxidative stress pathways to generate reactive oxygen species (ROS). Upon 808 nm laser irradiation, IR820 is activated to exert a combined therapeutic effect. It mediates PDT to generate ROS, while the localized hyperthermia induced by PTT causes direct cellular apoptosis and facilitates DOX release, thereby enhancing therapeutic efficacy. Additionally, the nanosystems integrate magnetic resonance imaging (MRI) and near-infrared fluorescence (NIR) imaging capabilities, enabling real-time treatment monitoring and precise diagnosis. In vivo studies demonstrated that MnCO3–BSA@DOX/IR820 nanosystems effectively inhibit tumor growth without causing notable damage to normal tissues. Therefore, this pH-responsive and MRI/NIR imaging-guided nanoplatform represents a targeted theranostic system for pancreatic cancer, enabling chemo-PTT/PDT synergy.