Simultaneously Enhancing NIR-II Emission, Type-I, and Type-II Photosensitization Through Acceleration of...

Area of Science:

• Biomedical Engineering
• Materials Science
• Oncology

Background:

• Phototheranostic agents utilizing near-infrared (NIR) excitation show promise for cancer imaging and therapy.
• Limitations in energy gap law reduce fluorescence and photosensitization, hindering combined therapy efficacy.

Purpose of the Study:

• To enhance NIR-II emission, type-I and type-II photosensitization efficiencies in NIR-excitable phototheranostic agents.
• To develop an effective strategy for "acceleration of charge-separated-state formation" to overcome current limitations.

Main Methods:

• Optimized chemical structure and aggregated architecture of phototheranostic agents (8TP-IF to 6TP-IH).
• Investigated the transition rate from localized excited (LE) to charge-separated (CS) state.
• Encapsulated the optimized agent (6TP-IH) into nanoparticles (NPs) for in vitro and in vivo studies.

Main Results:

• Significantly improved charge-separated-state formation rate in 6TP-IH compared to 8TP-IF.
• Enhanced fluorescence, hydroxyl radical (•OH), and singlet oxygen (¹O₂) generation efficiencies of 6TP-IH upon NIR excitation.
• Demonstrated precise tumor imaging, robust tumor ablation, and effective immunogenic cell death (ICD) activation via synergistic photodynamic and photothermal therapy.

Conclusions:

• The developed 6TP-IH NPs effectively enable NIR-II fluorescence image-guided tumor combination therapy.
• Achieved a 99.1% tumor inhibition rate in a 4T1 tumor-bearing mouse model.
• The strategy of accelerating charge-separated-state formation is a viable approach for advanced phototheranostic agents.