Water-soluble fluorescence-switching polymers for super-resolution lysosome imaging

Ming-Qiang Zhu1,  Chong Li2,  Zhe Hu2,  Matthew Aldred2
1Huazhong University of Science and Technology, 2


Abstract

Photochromic materials and fluorescent dyes have been progressed separately until recently, when their combination produces novel fluorescence photoswitching. Of the particular properties desired are good photoswitching behavior and sensory fluorescence.Here we integrated a photoswitchable quencher, a highly emissive yet pH sensitive fluorophore, and a water-soluble polymer with controlled hydrophilicity into a functional nanosystem. The photoswitching quencher is based on dithienylethene (DTE) unit, while the pH-sensitive emitter is naphthalimide (NI) unit and the water-soluble polymer is obtained from polymerization of N-isopropylacrylamide (NIPAM). Together, these three units create a novel super-resolution Lysosome-Highlighter, although individually none can function as a LysoTracker. Because the emitter is sensitive to pH, the resulting polymer becomes highly fluorescent in acidic lysosomes. In addition, photoswitching regulates the fluorescence on and off and thus enables super-resolution localization of fluorescent polymers with sub-40 nm spatial resolution in imaging subcellular organelles. Thus, the concept presented here, including the photoswitchable DTE-pH-sensitive NI dyad, is promising to guide the development of future-generation super-resolution imaging agents.