Self-Adaptive Charge Transfer States in Aqueous Solutions Promote Fast Intersystem Crossing in a Photosensitizer for...

Area of Science:

• Photochemistry
• Materials Science
• Biomedical Engineering

Background:

• Designing effective photosensitizers (PSs) for photodynamic therapy (PDT) in aqueous environments is challenging due to reduced intersystem crossing (ISC) rates and reactive oxygen species (ROS) yields.
• Conventional PS design strategies optimized for organic solvents often fail in aqueous solutions, limiting their therapeutic potential.

Purpose of the Study:

• To develop a high-performance PS with enhanced ISC rates and ROS yields in aqueous solutions for improved PDT.
• To investigate a novel design principle utilizing aqueous solvent properties to promote charge transfer and optimize excited-state evolution.

Main Methods:

• Construction of a new PS, Cy5-PCZ, designed to self-adaptively generate charge transfer singlet (¹CT) and triplet (³CT) states in water.
• Utilized transient absorption spectroscopy and theoretical calculations to analyze ISC rates and ROS yields.
• Evaluated the in vitro and in vivo efficacy of Cy5-PCZ-mediated PDT in cancer models.

Main Results:

• Cy5-PCZ demonstrated a significantly faster ISC time (∼5 ps) compared to conventional Cy5 (∼580 ps) in aqueous solutions.
• Markedly increased yields of both type I and type II ROS were observed with Cy5-PCZ.
• Cy5-PCZ effectively induced cancer cell apoptosis and pyroptosis, suppressed tumor growth, and reduced lung metastasis in mouse models at low concentrations.

Conclusions:

• The study presents a rational design principle for creating high-performance PSs in aqueous media by leveraging charge transfer mechanisms.
• Cy5-PCZ shows great promise for enhancing PDT efficacy in biological applications due to its optimized photophysical properties in water.
• This approach offers a pathway to overcome limitations of traditional PS design in aqueous environments for cancer treatment.