Latest developments in photosensitizers: improving stability, specificity and responsiveness.

Area of Science:

• Biochemistry
• Materials Science
• Oncology

Background:

• Photodynamic therapy (PDT) is an emerging anticancer strategy.
• PDT relies on photosensitizers (PSs) to generate cytotoxic reactive oxygen species (ROS) upon light activation.
• Optimizing PSs is crucial for enhancing therapeutic efficacy and minimizing side effects.

Purpose of the Study:

• To review recent advancements in photosensitizer (PS) design for photodynamic therapy (PDT).
• To highlight strategies for improving PS stability, specificity, and responsiveness.
• To discuss challenges and future directions in PS development for cancer treatment.

Main Methods:

• Structural modifications of PSs, including D-A type structures, polymethine chain shortening, and incorporation of rigid cyclic segments.
• Encapsulation of PSs in nanocarrier systems such as extracellular vesicles and liposomes.
• Development of stimulus-responsive PSs targeting tumor microenvironment (TME) factors like pH, viscosity, and ROS levels.

Main Results:

• Chemical modifications and nanocarrier systems enhance PS stability and delivery.
• Stimulus-responsive designs improve targeting precision and reduce off-target toxicity.
• Strategies like organelle-specific localization and antibody conjugation increase PS specificity.

Conclusions:

• Significant progress has been made in optimizing PSs for PDT through structural, nanocarrier, and stimulus-responsive approaches.
• Challenges remain in balancing photostability, biocompatibility, and clinical translatability.
• Continued innovation in PS design is essential for advancing PDT in cancer therapy.