Thermally Activated Delayed Fluorescence-Guided Photodynamic Therapy Through Skeleton-Homologous Nanoparticles: a...

Area of Science:

• Biomedical Engineering
• Nanotechnology
• Photodynamic Therapy

Background:

• Photodynamic therapy (PDT) guided by photoluminescence imaging faces challenges from tissue autofluorescence and PDT photoproducts.
• Developing time-resolved imaging (TRI)-guided PDT using long-lived emission pathways like thermally activated delayed fluorescence (TADF) is crucial but difficult due to triplet state competition.

Purpose of the Study:

• To design and construct skeleton-homologous nanoparticles for in vivo TRI-guided PDT, addressing the limitations of current theranostic approaches.
• To achieve simultaneous TRI and PDT using a single nanoparticle system with minimized phase separation and shared photoexcitation.

Main Methods:

• Engineered skeleton-homologous nanoparticles with a lipophilic TADF core for TRI and an amphiphilic photosensitizer shell for PDT.
• Utilized the same donor-acceptor skeleton for both components to ensure compatibility and shared long-wavelength photoexcitation.
• Incorporated a chloropropylamine group for endoplasmic reticulum targeting to enhance PDT efficacy.

Main Results:

• Achieved the first in vivo demonstration of TRI-guided PDT using the developed nanoparticle system.
• The TADF core provided a clear TRI signal with a delayed fluorescence lifetime of 40 µs.
• Demonstrated a high signal-to-background ratio (45.25) and significant PDT effects in a mouse model of deep-seated kidney cancer.

Conclusions:

• The developed skeleton-homologous nanoparticles offer a novel strategy for high-contrast, efficient theranostic applications.
• This approach successfully overcomes the limitations of conventional photoluminescence imaging-guided PDT.
• The material design provides a foundation for advanced theranostic systems with improved imaging and therapeutic capabilities.