One-Pot Conversion of Acridines Into Phototherapeutic Near-Infrared Spirocyanines

Area of Science:

• Organic Chemistry
• Materials Science
• Biomedical Imaging

Background:

• Polymethine cyanines face limitations in optical properties for bio-imaging and phototherapy due to rapid nonradiative transitions.
• Developing novel cyanine dyes with improved photophysical properties is crucial for advanced biomedical applications.

Purpose of the Study:

• To synthesize a small-sized, spirocycle-fused trimethine acridinocyanine (SpiroCY) with enhanced optical properties.
• To investigate the mechanism of SpiroCY synthesis and its photophysical behavior.
• To evaluate SpiroCY as a mitochondria-targeted imaging agent and a phototherapeutic agent for cancer treatment.

Main Methods:

• One-pot oxidative trimerization using oxygen as the oxidant to synthesize SpiroCY.
• Theoretical calculations using the Automated Design of Chemical Reaction (ADCR) program to elucidate the reaction mechanism.
• Evaluation of SpiroCY for near-infrared (NIR-I and NIR-II) cell imaging and photodynamic therapy (PDT) efficacy.

Main Results:

• SpiroCY was synthesized via a radical cascade reaction mechanism involving O2-derived radicals.
• Spiro-functionalization significantly improved brightness and suppressed H-aggregation, enabling mitochondria-targeted NIR-I and NIR-II imaging at low doses (10-100 nM).
• SpiroCY demonstrated potential as an antitumor drug and a Type-I photosensitizer, generating reactive oxygen species (ROS) under 808 nm light irradiation for efficient PDT.

Conclusions:

• SpiroCY represents a novel class of spiro dyes with superior photophysical properties for NIR imaging and phototherapy.
• The study provides mechanistic insights into spirocyclic effects on dye properties and a new avenue for dye functionalization.
• Spiro dyes show promise as advanced agents for targeted bio-imaging and photodynamic cancer therapy.