Manipulation of ROS-Responsiveness of Dextran with Thioether Side Chains

Reactive oxygen species (ROS) -responsive polymers based on thioether are widely used for drug delivery platforms for inflammation. However, the responsiveness of polymers containing thioether is not tunable toward acute and chronic inflammation, respectively. Here, two kinds of thioether molecules are grafted onto the hydroxyl groups of dextran in a simple and efficient manner. The grafted dextrans possess similar macromolecular structure and molecular weight and easily form nanoparticles. Cytotoxicity experiments confirm the good biocompatibility and antioxidant properties of the nanoparticles. The grafted dextran responds to typical ROS molecules in the order of ClO − , KO 2 , and H 2 O 2 . As for H 2 O 2 , the grafted dextran with ester group responds much faster than that of the carbonate group, with the former responding six times faster than the latter, which provides opportunities for the treatment of acute and chronic inflammation, respectively. It is demonstrated that the ester group near the thioether renders the oxidation reaction easier than that of carbonate groups because of its lower energy barrier, which is directly confirmed by an in situ nuclear magnetic resonance (NMR) investigation of the reaction between model molecules and H 2 O 2 and theoretical computational simulations. In conclusion, the ROS responsiveness of grafted dextran can be tunable and the grafted dextran exhibits the potential application in inflammation-involved disease.