Peroxide-Simulating and GSH-Depleting Nanozyme for Enhanced Chemodynamic/Photodynamic Therapy via Induction of...

Area of Science:

• Biomedical Engineering
• Nanotechnology
• Cancer Therapy

Background:

• Reactive oxygen species (ROS) generation via photodynamic therapy (PDT) and chemodynamic therapy (CDT) shows promise for cancer treatment.
• Tumor microenvironment limitations like hypoxia and ROS scavengers hinder ROS-related cancer therapy efficacy.

Purpose of the Study:

• To develop a novel nanozyme, MLP@DHA&Ce6, for enhanced cancer therapy by generating multisource ROS.
• To overcome the challenges posed by the tumor microenvironment to ROS-based treatments.

Main Methods:

• Synthesized a lipid-supported manganese oxide nanozyme (MLP@DHA&Ce6) with a MnO2 nano-shell encapsulating dihydroartemisinin (DHA) and photosensitizer Ce6.
• Investigated ROS generation through nanozyme-catalyzed CDT, Ce6-mediated PDT, and Mn2+-catalyzed Fenton reactions.
• Evaluated the nanozyme's ability to produce oxygen, deplete glutathione, and induce ferroptosis.

Main Results:

• MLP@DHA&Ce6 releases Mn2+ ions and O2, enhancing Ce6-mediated PDT.
• The nanozyme effectively depletes glutathione, maintaining ROS activity within tumor cells.
• The combined ROS generation and ferroptosis induction by MLP@DHA&Ce6 demonstrated significant in vivo therapeutic effects.

Conclusions:

• MLP@DHA&Ce6 effectively generates multisource ROS and induces ferroptosis, overcoming tumor microenvironment limitations.
• This nanozyme platform offers a promising strategy for enhancing ROS-related cancer therapies.