Activatable Heavy-Atom-Free Photosensitizer with Large Stokes Shift and a NIR-II Emission Harnessing Rhodamine...

Area of Science:

• Organic Chemistry
• Materials Science
• Biomedical Engineering

Background:

• Activatable photosensitizers (PSs) generate singlet oxygen (¹O₂) on demand, minimizing damage to healthy tissues.
• Heavy-atom-free PSs offer advantages like low toxicity, long excited-state lifetimes, and cost-effectiveness.
• Near-infrared II (NIR-II) window emission is crucial for deep-tissue imaging due to reduced light scattering and absorption.

Purpose of the Study:

• To design and synthesize novel heavy-atom-free photosensitizers emitting in the NIR-II window.
• To develop activatable PSs using rhodamine derivatives for targeted photodynamic therapy (PDT).
• To demonstrate the potential of these PSs for Cu²⁺/pH-triggered activation and in vitro PDT efficacy.

Main Methods:

• One-step synthesis of heavy-atom-free PSs via rhodamine derivative and thiophene aldehyde condensation.
• Characterization of photophysical properties, including emission spectra and Stokes shift.
• Development of Cu²⁺/pH-activatable PSs utilizing rhodamine's spirocyclization mechanism.
• In vitro evaluation of the synthesized PSs for photodynamic therapy effectiveness.

Main Results:

• A series of heavy-atom-free PSs were successfully synthesized.
• Compound 2b-3T exhibited NIR-II emission (810 nm maxima, 1140 nm tail) and a large Stokes shift (178 nm).
• Carboxylic acid functional groups enabled the creation of Cu²⁺/pH-activatable PSs via spirocyclization.
• In vitro studies confirmed the effectiveness of these activatable PSs in photodynamic therapy.

Conclusions:

• Novel heavy-atom-free photosensitizers emitting in the NIR-II window were developed.
• The functional carboxylic acid groups provide a versatile platform for creating activatable photosensitizers.
• Cu²⁺/pH-activatable PSs were successfully demonstrated, showing potential for targeted photodynamic therapy.