Bimetallic ions-doped carbon dots nanotheranostics for imaging-guided macrophage polarization/ROS scavenging in acute pancreatitis

Acute pancreatitis (AP) is a life-threatening inflammatory disease of the pancreas. When AP occurs, macrophages are recruited and stimulated to pro-inflammatory M1 phenotype, releasing pro-inflammatory factors and reactive oxygen species (ROS). Therefore, macrophage polarization is one of the most promising therapeutic strategies for AP therapy. In this study, we designed a chitosan-based inflammation-responsive nanosystem, which successfully integrates ROS scavenging, macrophage polarization and multimodal imaging for AP treatment. Through a convenient hydrothermal method, Ce and Gd bimetallic ions doped CDs (Ce/Gd-CDs) were successfully constructed, which showed excellent ROS scavenging and magnetic resonance imaging (MRI) function. Then, chitosan was employed as an inflammation-responsive carrier for loading with both Ce/Gd-CDs and resveratrol (RES), forming multifunctional therapeutic agent CDs/RES@CS NPs (CRCS). The pH-sensitive chitosan carriers were able to reduce the biotoxicity of Ce/Gd-CDs and RES and prolong their in vivo circulation time, thus advancing their utilization. Taken together, the in vitro and in vivo studies of CRCS displayed a favorable synergistic potency of ROS scavenging, macrophage polarization and multimodal imaging, significantly reducing AP. Our design expands the biological application of multifunctional nano-enzymes while providing a novel strategy toward constructing microenvironment-responsive therapeutic platforms for inflammatory disease treatment.