Tuning Organelle Specificity and Photodynamic Therapy Efficiency by Molecular Function Design

Area of Science:

• Organic Chemistry
• Photochemistry
• Biomedical Engineering

Background:

• Organic photosensitizers (PSs) are crucial for photodynamic therapy (PDT), but design guidelines are scarce.
• Triphenylamine-azafluorenone core provides a versatile platform for PS development.

Purpose of the Study:

• To establish structure-property-application relationships for novel PSs.
• To investigate the role of cationization and aggregation-induced emission (AIE) in PDT efficiency.
• To explore combination therapy of PDT with radiotherapy.

Main Methods:

• Design and synthesis of triphenylamine-azafluorenone-based PSs.
• Systematic study of structure-property relationships, including fluorescence and reactive oxygen species (ROS) generation.
• Evaluation of PS efficacy in targeting mitochondria and lipid droplets.
• Assessment of AIE properties and their impact on PDT.

Main Results:

• Cationization effectively targets PSs to mitochondria, enhancing PDT efficiency.
• PSs exhibiting aggregation-induced emission (AIE) showed increased fluorescence and ROS generation in aggregate states.
• Mitochondrion-targeting cationized PSs demonstrated superior PDT efficacy compared to non-ionized PSs targeting lipid droplets.
• Combined PDT and radiotherapy enhanced cancer cell killing.

Conclusions:

• Cationization is a key strategy for developing efficient mitochondrion-targeting PSs for PDT.
• AIE properties significantly boost PS performance by restricting intramolecular motion and enhancing intersystem crossing.
• Combining AIE-based PDT with radiotherapy offers a promising approach for improved cancer therapy.