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Updated: Sep 18, 2025
Author Spotlight: Tracing the Ferroptotic Signatures and Cell Death Dynamics in Medulloblastoma for Advanced Therapeutics
Published on: March 15, 2024
Multistimulus-responsive oxidative stress/ferroptosis combination anti-tumor nano-enzyme constructed based on glucose
Miaoxin Chen1, Gaoyang Li1, Xiaoyu Ji2
1State Key Laboratory of Chemical Engineering and School of Chemistry & Molecular Engineering, East China University of Science and Technology, Shanghai 200237, PR China.
Abstract:
Enzymes show excellent specificity and high efficiency in the treatment of various diseases, how to avoid inactivation during human circulation and improve the transfection are still challenges. Based on the importance of glucose enzymes (GOx) in the process of ferroptosis, we developed a nano-enzyme system containing GOx based on the self-assembly of near-infrared (NIR)-responsive Prussian blue (PB) and the thermosensitive polymer PEG-P(AAm-co-AN) (PEG-PAA). PB provided both photothermal effects and peroxidase-like activity, while the PEG-PAA shell shielded and protected GOx. Upon NIR irradiation, the PB/GOx@PAA-PEG nanoparticles exploited PB's photothermal properties to reach the upper critical solution temperature (UCST) of PEG-PAA, triggering a hydrophilic-hydrophobic transition in the polymer shell. This transition caused GOx exposed to glucose, switching on the conversion of glucose into hydrogen peroxide, which was further catalyzed into hydroxyl radical (•OH) by PB. Cell-based experiments investigated the biocompatibility and intracellular ROS levels after incubation with PB/GOx@PAA-PEG nanoparticles. The cytotoxicity and the mechanism of cell death were further explored by using various indicators such as vitamin E (VE), glutathione (GSH). This study demonstrated a low side-effect, high-efficiency anti-tumor nano-enzyme system with synergistic anti-tumor effects of oxidative stress and ferroptosis, providing effective strategies for multiple tumor therapies.
Insights
This study introduces a novel nano-enzyme system for cancer therapy. The system uses near-infrared light to activate glucose oxidase, generating reactive oxygen species and inducing ferroptosis for effective tumor treatment with minimal side effects.
Area of Science:
- Biomedical Engineering
- Nanotechnology
- Enzyme Engineering
Background:
- Enzymes offer high specificity and efficiency for disease treatment but face challenges in circulation stability and transfection.
- Glucose oxidase (GOx) plays a crucial role in ferroptosis, a key process in cancer therapy.
- Developing stable and effective nano-enzyme delivery systems is critical for therapeutic applications.
Purpose of the Study:
- To develop a novel nano-enzyme system for enhanced cancer therapy by combining photothermal effects with enzyme activity.
- To improve the stability and targeted delivery of glucose oxidase (GOx) using a near-infrared (NIR)-responsive Prussian blue (PB) and thermosensitive polymer (PEG-PAA) shell.
- To investigate the synergistic anti-tumor effects of oxidative stress and ferroptosis induced by the nano-enzyme system.
Main Methods:
- Fabrication of PB/GOx@PAA-PEG nanoparticles utilizing self-assembly of NIR-responsive Prussian blue (PB) and thermosensitive PEG-PAA.
- NIR irradiation to trigger a hydrophilic-hydrophobic transition of the PEG-PAA shell, exposing GOx to glucose.
- In vitro studies using cell-based assays to evaluate biocompatibility, intracellular reactive oxygen species (ROS) levels, cytotoxicity, and cell death mechanisms.
Main Results:
- The developed PB/GOx@PAA-PEG nanoparticles demonstrated NIR-triggered release and activation of GOx.
- NIR irradiation induced localized hyperthermia and efficient generation of hydroxyl radicals (•OH) via glucose oxidation and PB catalysis.
- Cell-based experiments confirmed good biocompatibility, elevated intracellular ROS, and synergistic anti-tumor effects through oxidative stress and ferroptosis.
Conclusions:
- The nano-enzyme system exhibits high efficiency and low side effects for cancer therapy.
- The synergistic action of photothermal therapy, oxidative stress, and ferroptosis provides a promising strategy for multi-modal tumor treatment.
- This study offers effective strategies for developing advanced nano-therapeutics for various cancers.
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