Inflammatory Cell‐Inspired Cascade Nanozyme Induces Intracellular Radical Storm for Enhanced Anticancer Therapy

Abstract

Manipulating intracellular levels of reactive oxygen and nitrogen species (RONS) is of great potential for cancer treatment. Inspired by the natural mechanism of a radical storm in inflammatory cells via activated and regulatable biocatalysis, the authors herein report a self‐powered nanozyme that can enable RONS production in tumor cells via cascade reactions. The nanozymes are constructed via glucose oxidase (GOx)‐templated inverse microemulsion polymerization from acrylamide, arginine‐acrylamide, ferrocene‐acrylate, and N,N′‐bis(acryloyl)cystamine, followed by surface coating with hyaluronic acid. After targeted delivery into cancer cells, the nanozymes are dissociated by intracellular glutathione to release GOx, which decomposed glucose to generate gluconic acid and H2O2. Under such acidified conditions, H2O2 efficiently oxidized pendant arginine residues to produce nitric oxide , transformed into a highly toxic hydroxyl radical and superoxide anion via ferrocene‐mediated Fenton reaction and Haber–Weiss cycle, and simultaneously generated peroxynitrite anion via reaction between NO and ·O2−, thus provoking the RONS radical storm to effectively eradicate A549 tumor cells both in vitro and in vivo. This nature‐inspired enzyme‐chemical dynamic therapy may provide a promising modality for anti‐cancer treatment.

The Key Effect of Carboxyl Group and CuN2O2 Coordinate Structure for Cu, N Co‐Doped Carbon Dots with Peroxidase‐Like Property

“…The kinetic parameters involving the values of maximum initial velocity ( v max ) and Michaelis‐Menten constant ( K m) were demonstrate by the steady–state kinetic and Lineweaver Burk double reciprocal plot (Figure 4b; Figure S10, Supporting Information). [ 48,49 ] The value of v max is 6.56*10 −7 m s −1 and K m value is 1.37 m m . Notably, the catalytic performance of Cu‐CDs‐300 is significantly higher than those of Cu‐CDs‐250 and Cu‐CDs‐350 under the same conditions and 6.56 times higher than that of horseradish peroxidase with v max 1*10 −7 m s −1 (Table S3, Supporting Information).…”

Cascade strategy for glucose oxidase-based synergistic cancer therapy using nanomaterials

“…220 More recently, a scheme manipulating reactive oxygen and nitrogen species (RONS) to induce intracellular radical storms was demonstrated by Liu and colleagues. 221 The enhanced oxidative stress elicited by RONS would eventually trigger cancer cell apoptosis; more importantly, NO can undergo further reaction with O 2 À to produce a more toxic reactive nitrogen species (RNS) than most ROS, peroxynitrite anion (ONOO À ). The researchers exploited a GOx-based nanozyme (Arg/Fc@GOx/ HA) to induce drastic RONS radical storms via cascade reactions and validated its antitumor effectiveness with minimal negative effects through in vitro and in vivo evaluation.…”