Hetero-Trimetallic Atom Catalysts Enable Targeted ROS Generation and Redox Signaling for Intensive Apoptosis and...

Area of Science:

• Biomedical Engineering
• Nanotechnology
• Catalysis

Background:

• Reactive oxygen species (ROS) are vital in cellular signaling but challenging to engineer in nanozymes due to efficiency and toxicity issues.
• Current nanozyme designs struggle with low catalytic activity, high toxicity, and off-target consumption of ROS.

Purpose of the Study:

• To design novel hetero-trimetallic atom catalysts (TACs) for efficient ROS generation and targeted tumor therapy.
• To overcome the limitations of existing nanozymes regarding catalytic efficiency, toxicity, and specificity.

Main Methods:

• Developed 3D network TACs using Cu, Co, and Fe hetero-single atoms on a MIL-101(Fe) scaffold with N and P ligands.
• Utilized nanovesicle membranes for homologous targeting, recognition, and endocytosis to enhance nanozyme stability and reduce off-target effects.
• Investigated the in situ ROS generation and its impact on tumor microenvironment oxidative stress and apoptosis pathways.

Main Results:

• Uniform dispersion of hetero-single atoms in TACs prevented sintering and boosted catalytic activity for ROS generation.
• Nanovesicle membranes ensured targeted accumulation and uptake, mitigating toxicity and off-target issues.
• In situ ROS blooms acted as redox signals, regulating oxidative stress and inducing apoptosis and ferroptosis concurrently.

Conclusions:

• The developed TACs demonstrate high catalytic efficiency and targeted delivery for effective ROS generation in tumor therapy.
• This approach addresses key limitations of nanozymes, showing promise for biomedical applications.
• TACs effectively modulate tumor microenvironment and induce cell death pathways, highlighting their therapeutic potential.