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

Abstract

Abstract 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‐PEG 8 ‐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.