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

Low-molecular-weight compounds of certain structural features may form coacervates through liquid-liquid phase separation (LLPS). These coacervates can enter mammalian cells and affect cellular physiology. Controlling the properties of the coacervates inside cells, however, is a challenge. Here, we report photochemical reactions of spiropyran (SP)-based coacervates with two wavelengths of light, in vitro, in the cell, and in animals, generating reactive oxygen species (ROS) for photo-controlled cell killing. We identify an SP-containing compound, SP-PEG8-SP, that forms coacervates (SP-C) in the aqueous solution. Photo illumination by a UV light triggers the isomerization of SP to merocyanine (MC), switching SP-C to the fluorescent coacervates MC-C. A visible light converts MC-C back to SP-C and induces ROS generation. Notably, coacervate formation increases the compound's ROS generation efficiency. The SP-C/MC-C coacervate system (collectively called spiropyran coacervates) can spontaneously enter cells, and a dual-wavelength-controlled reversible on/off switch and spatiotemporal-resolved ROS production is realized within the cytoplasm. Light-induced ROS generation leads to cytotoxicity to cancer cells, tumor organoids, and tumors in vivo, supporting spiropyran coacervates' potential use as coacervate photosensitizers in photodynamic therapies.