Bioinspired Construction of an Enzyme-Mimetic Supramolecular Nanoagent for RNS-Augmented Cascade Chemodynamic Therapy

Inspired by natural enzymes, specific enzyme-like cascade catalytic reactions can be obtained by imitating the metal active sites of natural enzymes and assembling inorganic materials at the molecular level via supramolecular interactions, which can greatly expand their application in biology. Herein, it is reported that a bioinspired SNP/MgMnFe-LDH (denoted as S2MFL) supramolecular nanoagent has been successfully synthesized via the intercalation between nitroprusside (SNP) and MgMnFe-layered double hydroxides (denoted as 2MFL). Initially, the resulting S2MFL possesses peroxidase-, catalase-, and oxidase (OXD)-like activities under tumor microenvironment (TME) stimulation. It should be noted that this S2MFL demonstrates a high OXD-like activity rate level of 9.508 × 10^-6 Ms^-1 in the chemodynamic therapy (CDT) study. Furthermore, the superoxide anions (O₂^•-) generated via OXD-like activity can react with NO (GSH-responsive), followed by the production of reactive nitrogen species (RNS). The synergistic reactive oxygen species (ROS) and RNS generation destroys the intratumoral redox balance and extensively promotes cancer cell inhibition without additional energy introduction and has excellent T₁/T₂-weighted magnetic resonance imaging (MRI) ability. Overall, this RNS-enhanced CDT strategy provides a novel approach for TME-mediated therapy.