A Molybdenum Disulfide Nanozyme with Charge‐Enhanced Activity for Ultrasound‐Mediated Cascade‐Catalytic Tumor Ferroptosis

Abstract

The deficient catalytic activity of nanozymes and insufficient endogenous H2O2 in the tumor microenvironment (TME) are major obstacles for nanozyme‐mediated catalytic tumor therapy. Since electron transfer is the basic essence of catalysis‐mediated redox reactions, we explored the contributing factors of enzymatic activity based on positive and negative charges, which are experimentally and theoretically demonstrated to enhance the peroxidase (POD)‐like activity of a MoS2 nanozyme. Hence, an acidic tumor microenvironment‐responsive and ultrasound‐mediated cascade nanocatalyst (BTO/MoS2@CA) is presented that is made from few‐layer MoS2 nanosheets grown on the surface of piezoelectric tetragonal barium titanate (T‐BTO) and modified with pH‐responsive cinnamaldehyde (CA). The integration of pH‐responsive CA‐mediated H2O2 self‐supply, ultrasound‐mediated charge‐enhanced enzymatic activity, and glutathione (GSH) depletion enables out‐of‐balance redox homeostasis, leading to effective tumor ferroptosis with minimal side effects.

Piezoelectric Metal–Organic Frameworks Based Sonosensitizer for Enhanced Nanozyme Catalytic and Sonodynamic Therapies

“…Therefore, accurate electrical stimulation tools must be developed to improve the effectiveness of the nanozyme catalytic therapy. 9 Piezoelectric materials, such as BaTiO 3 , ZnO, and BiFeO 3 , are materials with a noncentrosymmetric crystal structure that can generate built-in electric fields in response to external mechanical stimuli. 10−13 Among these mechanical stimuli, ultrasound (US) with a high penetrating ability can be used to excite piezoelectric materials to generate a built-in field, which can reconfigure the electrostatic field of the nanozymes and, consequently, improve their catalytic efficiency.…”

“…However, electrical stimulation often requires the use of high current and large equipment because the external electric fields cannot precisely target the nanozymes. Therefore, accurate electrical stimulation tools must be developed to improve the effectiveness of the nanozyme catalytic therapy …”

The applications of nanozymes in cancer therapy: based on regulating pyroptosis, ferroptosis and autophagy of tumor cells

“…Therefore, the BTO/MoS 2 @CA nanozyme under the action of US irradiation can overcome the defects of insufficient catalytic activity and insufficient endogenous H 2 O 2 in the TME, showing excellent in vivo antitumor efficiency. 64…”

“…Therefore, the BTO/ MoS 2 @CA nanozyme under the action of US irradiation can overcome the defects of insufficient catalytic activity and insufficient endogenous H 2 O 2 in the TME, showing excellent in vivo antitumor efficiency. 64 Yuan et al encapsulated CuCP molecules in liposome NPs to construct CuCP Lipo NP nanozymes with effective biocom-patibility and stability. This nanozyme displayed POD-like activity and photothermal properties, catalyzing the conversion of H 2 O 2 into • OH through the Fenton reaction and the consumption of GSH to generate GSSG, thus depleting the GSH level in tumor masses and producing a high level of LPOs, ultimately leading to the ferroptosis of the tumor cells.…”

Silk Fibroin Nanozyme Hydrogel with Self-Supplied H2O2 for Enhanced Antibacterial Therapy

“…Nanomaterials based artificial peroxidase mimicking enzymes, as a typical nanozyme, have been intensively studied in antibacterial therapies. − Such peroxidase-like nanozymes can catalyze hydrogen peroxide (H 2 O 2 ) into reactive oxygen species (ROS) in a physiological environment, which inactivates pathogens by irreversibly oxidizing biomolecules and disturbing intracellular physiological activities, accelerating bacteria-infected wound healing and curing tissues damage in cooperation with insulin-loaded micelles. − For obtaining a satisfactory antibacterial effect, the supply of H 2 O 2 is one of the key factors determining the ROS production. − Therefore, the application of materials with peroxidase-like enzyme properties should be used in H 2 O 2 -riched tissue or should be supplied with exogenous H 2 O 2 . − Nevertheless, the concentration of H 2 O 2 was insufficient in some cases, and liquid exogenous H 2 O 2 could easily leak from encapsulating materials to nontarget healthy tissue. − For these reasons, nanozyme therapy with H 2 O 2 self-supplying strategy was increasingly studied to ensure therapeutic effect.…”