Supramolecular semiquinone radicals confined with DNAzymes for dissipative ROS generation and therapy

Abstract

Current reactive oxygen species (ROS)-regulating materials for disease treatments are always at turn-on state, leading to long-lasting inflammation and chronic wound healing. Inspired by the process of Coenzyme Q (CoQ)-mediated ROS formation in the mitochondrial electron transport chain (ETC), a dissipative ROS nanogenerator possessing energy storage function and horseradish peroxidase (HRP)-mimicking activity was realized by a type of ternary composite nanosheets. Specifically, semiquinone radicals generated from polydopamine polymerization were captured and stabilized by supramolecular DNA scaffolds hosts, i.e. G-quadruplexes/hemin (GH) complexes with large π-planes of bases and interplane spaces. As a consequence, semiquinone radicals served as electron donor to oxygen for generating H2O2 which could be utilized by the neighboring GH to generate hydroxyl radicals (•OH) at weakly acidic conditions. The cascade catalytic activity remained above 93% and 45% after 20, 60 days of storage in N2 saturated solution. However, it was consumptively attenuated (~22 h of dissipation duration) due to the electron depletion/exhaustion of semiquinone radicals at pathological conditions. Thereby, effective inhibition of tumor recurrence and wound infection, as well as accelerated tissue repair were achieved in tumor postoperative treatments. This system significantly advances ROS regulators for integrative therapy.