Phase-Separated Spiropyran Coacervates as Dual-Wavelength-Switchable Reactive Oxygen Generators

Area of Science:

• Biomaterials Science
• Supramolecular Chemistry
• Cellular Biology

Background:

• Low-molecular-weight compounds can form coacervates via liquid-liquid phase separation (LLPS).
• Coacervates can enter cells and influence cellular functions, but intracellular control remains difficult.
• Spiropyran (SP)-based compounds offer photochemical responsiveness.

Purpose of the Study:

• To develop photo-controllable coacervates for intracellular applications.
• To investigate the photochemical properties of spiropyran coacervates for generating reactive oxygen species (ROS).
• To evaluate the therapeutic potential of spiropyran coacervates in cancer treatment.

Main Methods:

• Synthesis of SP-PEG8-SP compound forming spiropyran coacervates (SP-C).
• Photochemical isomerization of SP to merocyanine (MC) using UV and visible light.
• In vitro, in-cell, and in vivo studies of coacervate behavior and ROS generation.
• Assessment of cytotoxicity against cancer cells, organoids, and tumors.

Main Results:

• SP-C undergoes reversible isomerization to fluorescent MC-C upon light stimulation.
• Coacervate formation enhances ROS generation efficiency.
• Spiropyran coacervates exhibit dual-wavelength-controlled on/off switching and spatiotemporal ROS production within cells.
• Light-induced ROS generation demonstrates significant cytotoxicity to cancer cells and tumors in vivo.

Conclusions:

• Spiropyran coacervates provide a platform for light-controlled intracellular ROS generation.
• The system allows for reversible on/off switching and precise spatial control of ROS production.
• Spiropyran coacervates show promise as photosensitizers for photodynamic cancer therapy.