Layered double hydroxide-based nanozyme for NO-boost multi-enzyme dynamic therapy with tumor specificity.

Area of Science:

• Biomedical Engineering
• Materials Science
• Nanotechnology

Background:

• Dual chemodynamic therapy (CDT) and nitric oxide (NO) therapy offer synergistic potential for improved cancer treatment efficacy.
• Designing multifunctional agents that integrate these therapeutic modalities remains a significant challenge in nanomedicine.

Purpose of the Study:

• To develop a novel nanozyme, termed LDHzyme, by confining L-arginine (L-Arg) onto manganese layered double hydroxide (Mn-LDH) nanosheets.
• To investigate the enzyme-like catalytic activities and therapeutic potential of the developed LDHzyme for cancer treatment.

Main Methods:

• Synthesis of LDHzyme through surface confinement of L-Arg on Mn-LDH nanosheets.
• Characterization of LDHzyme's peroxidase (POD), oxidase (OXD), and nitric oxide synthase (iNOS)-like activities.
• Evaluation of NO-enhanced reactive oxygen species (ROS) lethality and in vitro/in vivo anti-tumor efficacy in HeLa xenograft models.

Main Results:

• The LDHzyme exhibited high catalytic efficiency with a maximum velocity of 1.41 × 10⁻⁶ M s⁻¹, surpassing many existing nanozymes.
• LDHzyme demonstrated enhanced NO-mediated lethality of ROS, improving overall therapeutic efficacy.
• Significant inhibition of tumor growth was observed in both in vitro and in vivo models, validating the therapeutic potential.

Conclusions:

• The developed LDHzyme effectively integrates multiple enzyme-mimicking activities for enhanced cancer therapy.
• NO-enhanced multi-enzyme dynamic therapy (MDT) using LDH-based nanozymes presents a promising strategy for tumor growth inhibition.
• LDH-based nanozymes offer a viable platform for developing novel curative nanosystems against cancer.