Peroxide-Simulating and GSH-Depleting Nanozyme for Enhanced Chemodynamic/Photodynamic Therapy via Induction of Multisource ROS
Related Experiment Video
Updated: Aug 10, 2026
Photodynamic Therapy with Blended Conducting Polymer/Fullerene Nanoparticle Photosensitizers
Published on: October 28, 2015
Gang Liu1, Mingyu Liu1, Xiujing Li1
1The First Affiliated Hospital of Anhui University of Chinese Medicine, Hefei 230031, P. R. China.
Abstract:
Reactive oxygen species (ROS) generation, using photodynamic therapy (PDT) and chemodynamic therapy (CDT), is a promising strategy for cancer treatment. However, the production of ROS in tumor cells is often limited by hypoxia, insufficient substrates, and high level of ROS scavengers in a tumor microenvironment, which seriously affects the efficacy of ROS-related tumor therapies. Herein, we report a lipid-supported manganese oxide nanozyme, MLP@DHA&Ce6, by decorating a MnO2 nano-shell on the liposome loaded with dihydroartemisinin (DHA) and photosensitizer Ce6 for generating multisource ROS to enhance cancer therapy. MLP@DHA&Ce6 can be accumulated in tumors and can release active components, Mn2+ ions, and O2. The conjugate generates ROS via nanozyme-catalyzed CDT using DHA as a substrate, PDT through Ce6, and the Fenton reaction catalyzed by Mn2+ ions. The production of O2 from MnO2 enhanced Ce6-mediated PDT under near-infrared light irradiation. Meanwhile, MLP@DHA&Ce6 showed prominent glutathione depletion, which allowed ROS to retain high activity in tumor cells. In addition, the release of Mn2+ ions and DHA in tumor cells induced ferroptosis. This multisource ROS generation and ferroptosis effect of MLP@DHA&Ce6 led to enhanced therapeutic effects in vivo.
Insights
This study introduces a novel nanozyme, MLP@DHA&Ce6, that generates multiple sources of reactive oxygen species (ROS) to overcome tumor hypoxia and enhance cancer therapy effectiveness.
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.
More Related Videos
10:05Stimulation of Stem Cell Niches and Tissue Regeneration in Mouse Skin by Switchable Protoporphyrin IX-Dependent Photogeneration of Reactive Oxygen Species In Situ
Published on: May 8, 2020
11:04An In-House-Built and Light-Emitting-Diode-Based Photodynamic Therapy Device for Enhancing Verteporfin Cytotoxicity in a 2D Cell Culture Model
Published on: January 13, 2023
