Tumor microenvironment-responsive histidine modified-hyaluronic acid-based MnO2 as in vivo MRI contrast agent

Tumor microenvironment (TME)-responsive manganese dioxide (MnO2) nanoparticles as a good T1 contrast agent could reduce unwanted toxicity and improve the accuracy of cancer detection. Despite these distinct advantages of MnO2-based nanoparticles, their synthesis involves multi-step processes with relatively long synthesis times. In this study, we synthesized histidine-modified hyaluronic acid (HA-His), and the prepared HA-His conjugates quickly reduce permanganate to MnO2, leading to facile production of HA-His/MnO2 nanoparticles with good water-dispersibility and stability under biological conditions. The synthesized HA-His/MnO2 nanoparticles readily responded to the TME (low pH, high H2O2, and high glutathione), and they were internalized into SCC7 cells with high CD44 expression. Moreover, the systemically administered HA-His/MnO2 nanoparticles with biocompatibility were specifically accumulated in tumor tissues, thereby efficiently enhancing T1 contrast in MRI. Therefore, the HA-His/MnO2 nanoparticles synthesized herein can be used as a promising T1 contrast agent for tumor MR imaging.