Biocompatible nanocarriers that respond to oxidative environments via interactions between chitosan and multiple metal ions

Hydrogen peroxide (H(2)O(2)) functions as an early damage signal contributing to the oxidative stress response and can act as a trigger in smart oxidation-responsive drug delivery systems that are currently in development. Current H(2)O(2)-triggered oxidation-responsive polymeric systems are usually derived from chemical synthesis and rarely include natural polymers. Herein, we report two series of nanoparticle (NP) complexes prepared with the biopolymer chitosan (CS) and four different metal ions (Cu(2+), Ca(2+), Zn(2+), and Fe(3+)), defined as CSNPs-metal complexes (Series 1) and CS-metal complexes NPs (Series 2), which responded to oxidation by dissolving upon H(2)O(2) exposure. Experiments examining Nile red release and H(2)O(2)-triggered degradation confirmed that both series of complexes showed better sensitivity to oxidation than the CSNPs alone. Furthermore, preliminary cytotoxicity and histological observations indicated that the two series exhibited little or no cytotoxicity and generated a mild inflammatory response. Our work provides a novel and promising strategy for developing NPs for use as intelligent oxidation-responsive systems.