A self-energized photodynamic therapy agent based on persistent luminescence nanoparticles

Area of Science:

• Nanotechnology
• Biomedical Engineering
• Oncology

Background:

• Photodynamic therapy (PDT) faces limitations including poor light penetration, photosensitizer instability, and tumor hypoxia.
• Persistent luminescence nanoparticles (PLNPs) offer potential but have limited reactive oxygen species (ROS) generation.
• Existing PDT methods require external light sources and specific photosensitizers.

Purpose of the Study:

• To develop a photosensitizer-free, pre-activatable nanoparticle platform for sustained ROS generation in PDT.
• To engineer composite nanoparticles that overcome the limitations of conventional PDT.
• To create a tumor microenvironment (TME)-responsive system for targeted cancer treatment.

Main Methods:

• Fabrication of ZGGC@PPy@MnO2 composite nanoparticles using a freeze-thaw-assisted centrifugation method.
• Utilizing a persistent luminescence core (ZGGC) for energy storage and polypyrrole (PPy) for enhanced ROS generation.
• Incorporating a MnO2 shell to alleviate tumor hypoxia and control ROS release.

Main Results:

• The developed nanoparticles achieved a nearly fourfold increase in ROS generation efficiency.
• Sustained ROS production for approximately 48 hours after a single ex vivo excitation.
• Demonstrated a high tumor inhibition rate of 73.2% in vivo.
• MnO2 shell effectively suppressed ROS in normal tissues while allowing activation in the tumor microenvironment.

Conclusions:

• The novel nanoplatform offers a promising alternative to conventional PDT by enabling sustained, targeted ROS generation.
• The photosensitizer-free and pre-activatable design simplifies treatment and improves safety.
• The developed nanoparticles effectively address tumor hypoxia and improve therapeutic outcomes.