Exploring the theranostic potential of carbon dots/Fe3 O4 superparticles for tumor-associated macrophage targeting and repolarization in colorectal cancer therapy via JAK/STAT and ERK/MAPK pathways

Colorectal cancer (CRC) immunotherapy has shown remarkable effects in only a small subset of patients, largely due to the influence of tumor-associated macrophages (TAMs), which play a key role in shaping the tumor immune microenvironment. In vivo dynamic imaging of TAMs is critical for personalized immunotherapy, as it enables the identification of patients likely to benefit from treatment and allows for real-time monitoring of therapeutic efficacy. Additionally, reprogramming the polarization state of TAMs from the pro-tumoral M2 phenotype to the anti-tumoral M1 phenotype represents a promising strategy to enhance immunotherapy outcomes. To address these challenges, we developed mannose-coated carbon dots/ Fe ₃ O ₄ superparticles (Mannose-DSPE-PEG@ Fe ₃ O ₄ /CDs) specifically designed to target TAMs. These superparticles combine the NMR-enhanced imaging capabilities of Fe ₃ O ₄ with the red fluorescence properties of carbon dots, enabling precise and non-invasive TAM imaging. Furthermore, Mannose-DSPE-PEG@ Fe ₃ O ₄ /CDs effectively reprogram TAMs from the M2 to M1 phenotype via the JAK/STAT and ERK/MAPK pathways, thereby reshaping the tumor immune microenvironment and exerting potent anti-tumor effects. In summary, this study demonstrates the potential of Mannose-DSPE-PEG@ Fe ₃ O ₄ /CDs as a theranostic nanoplatform for the monitoring and modulation of TAMs, offering a novel strategy for improving immunotherapy outcomes in colorectal cancer.