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

Abstract

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 T 1/T 2-weighted magnetic resonance imaging (MRI) ability. Overall, this RNS-enhanced CDT strategy provides a novel approach for TME-mediated therapy.

Multifunctional nanomedicines-enabled chemodynamic-synergized multimodal tumor therapy via Fenton and Fenton-like reactions

“…Additionally, SNP anion ([Fe-CN) 5 NO ]2- ), as a GSH-responsive NO donor, can release NO upon activation of GSH in tumor cells. Zhou et al successfully synthesized SNP/MgMnFe-LDH (S2MFL) supramolecular nano-reagent containing both Mn 2+ and SNP anions, and the synergistic effect of Mn 2+ and SNP can produce high levels of ONOO - to cause DNA fragmentation for synergistic CDT/NO anti-tumor 188 .…”

Nitroprusside and metal nitroprusside nano analogues for cancer therapy

“…[18]. Therefore, to improve the properties of SNP, researchers are designing and developing various SNP based nanomaterials by introducing metals in SNP complex or by incorporation of SNP in different nanomaterials for better therapeutic efficacy in order to overcome the complications and health consequences associated with the use of bare SNP [10,11,13,14,34,35]. These metal nitroprusside nano analogues possesses versatile physiochemical properties such as electrochemical, photocatalytic, photodegradation and sensing properties [36].…”

Antioxidant Cascade Nanoenzyme Antagonize Inflammatory Pain by Modulating MAPK/p‐65 Signaling Pathway

“…Therefore, the exogenous supplementation of SOD to remove excessive ROS and relieve chronic pain is a promising strategy. [ 8 ] Nevertheless, this strategy faces two dilemmas: 1) in vivo stable delivery of SOD molecules with resolved enzyme activity should be addressed; 2) synergistic enzyme catalysis should be designed to convert the produced H 2 O 2 catalyzed by SOD enzyme into lower oxidation O 2 for maximal ROS elimination. [ 9 ] Recently, increasing evidence has shown that inorganic antioxidant enzyme nanoparticles (NPs) can treat multiple diseases and show better stability and efficacy than natural enzymes.…”