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Water-Soluble Polymeric Photoswitching Dyads Impart Super-Resolution Lysosome Highlighters

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journal contribution
posted on 23.12.2014, 00:00 by Chong Li, Zhe Hu, Matthew P. Aldred, Ling-Xi Zhao, Hui Yan, Guo-Feng Zhang, Zhen-Li Huang, Alexander D. Q. Li, Ming-Qiang Zhu
In this report, 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.