An octupolar donor-acceptor dye exploiting aggregation-induced intersystem crossing for efficient ROS generation.

Area of Science:

• Materials Science
• Photochemistry
• Biomedical Engineering

Background:

• Photodynamic therapy (PDT) requires photosensitizers (PSs) to generate reactive oxygen species (ROS) for cancer treatment.
• Solid tumors often present hypoxic conditions, challenging the efficacy of traditional PDT PSs.

Purpose of the Study:

• To develop a heavy-atom-free photosensitizer that overcomes hypoxia limitations in PDT.
• To investigate the photophysical properties and therapeutic potential of a novel octupolar donor-acceptor dye, 3CN.

Main Methods:

• Synthesis and characterization of the 3CN dye and its nanoaggregates (3CNAgg).
• Evaluation of aggregation-induced intersystem crossing (AI-ISC) and triplet state generation.
• Assessment of Type I photosensitization and superoxide anion radical generation efficiency.
• In vitro photocytotoxicity assays against MDA-MB-231 cells under varying oxygen levels.
• In vivo studies using mouse xenograft models to evaluate tumor growth inhibition.

Main Results:

• 3CN self-assembles into stable nanoaggregates (3CNAgg) with prolonged triplet-state lifetimes.
• 3CNAgg exhibits efficient Type I photosensitization, generating superoxide radicals more effectively than rose bengal.
• Encapsulated 3CN (3CNEn) shows high therapeutic efficacy (IC50 = 8.6 μM) against triple-negative breast cancer cells, even under severe hypoxia (1% O2).
• In vivo studies demonstrated 100% tumor growth inhibition with minimal dark toxicity and intrinsic tumor targeting.

Conclusions:

• The heavy-atom-free dye 3CN and its nanoaggregates are promising photosensitizers for photodynamic therapy.
• 3CN-based PDT is effective against hypoxic tumors, offering a potential new therapeutic strategy for triple-negative breast cancer.
• The AI-ISC mechanism and Type I photosensitization contribute to the superior performance of 3CN.