Supramolecular Synthesis of Dithienylethene‐Albumin Complexes for Enhanced Photoswitching In Photoacoustic Imaging‐Guided Near‐Infrared Photothermal Therapy

Abstract Photoswitchable molecules can transit between two distinct isomers, enabling them to perform highly controllable imaging and therapeutic functions under certain laser irradiation. Dithienylethenes (DTEs), a class of photoswitchable molecules, exhibit strong thermal stability and high fluorescence quantum yield. However, the short excitation wavelength poses a significant challenge for the application of DTEs in photocontrolled imaging and therapy. Therefore, the development of DTE‐based derivatives or hybrid materials with near‐infrared (NIR) excitation is of great importance. In this study, two novel DTE derivatives are synthesized, whose closed‐ring isomers exhibit strong absorption in the NIR region. Compared with a DTE derivative previously reported and commercially available ones, these two DTE derivatives show higher photoswitching efficiency and extended absorption wavelength. Notably, the supramolecular assembly between DTE derivatives and albumin confers NIR‐activated photothermal switching ability on DTE molecules in aqueous solution. In addition, DTE‐albumin nanoparticles are further developed to enable photoswitchable photoacoustic imaging (PAI) and photothermal therapy (PTT) for in vivo antitumor applications. Finally, by integrating a thermo‐responsive free radical initiator into DTE‐albumin nanoparticles, photoswitchable PTT and chemodynamic therapy (CDT) are achieved, effectively inhibiting tumor growth and preventing tumor metastasis.