title: Lysosomal pH Decrease in Inflammatory Cells Used To Enable Activatable Imaging of Inflammation with a Sialic Acid Conjugated Profluorophore.
abstract: Inflammation causes significant morbidity and mortality, necessitating effective in vivo imaging of inflammation. Prior approaches often rely on combination of optical agents with entities specific for proteinaceous biomarkers overexpressed in inflammatory tissues. We herein report a fundamentally new approach to image inflammation by targeting lysosomes undergoing acidification in inflammatory cells with a sialic acid (Sia) conjugated near-infrared profluorophore (pNIR). Sia-pNIR contains a sialic acid domain for in vivo targeting of inflamed tissues and a pNIR domain which isomerizes into fluorescent and optoacoustic species in acidic lysosomes. Sia-pNIR displays high inflammation-to-healthy tissue signal contrasts in mice treated with Escherichia coli, Staphylococcus aureus, or lipopolysaccharide. In addition, inflammation-associated fluorescence is switched off upon antibiotics treatment in mice. This report shows the potentials of Sia-pNIR for activatable dual-modality inflammation imaging, and particularly the use of lysosomes of inflamed cells as a previously unappreciated biomarker for inflammation imaging.
authors.affiliation: †Department of Chemical Biology, College of Chemistry and Chemical Engineering, State Key Laboratory for Physical Chemistry of Solid Surfaces, the Key Laboratory for Chemical Biology of Fujian Province, the MOE Key Laboratory of Spectrochemical Analysis and Instrumentation, and Innovation Center for Cell Signaling Network, and ‡State Key Laboratory of Cellular Stress Biology, Innovation Center for Cell Signaling Network, School of Life Sciences, Xiamen University, Xiamen, 361005, China.
authors.forename: Mingzhu
authors.initials: M
authors.lastname: Yu
authors.affiliation: †Department of Chemical Biology, College of Chemistry and Chemical Engineering, State Key Laboratory for Physical Chemistry of Solid Surfaces, the Key Laboratory for Chemical Biology of Fujian Province, the MOE Key Laboratory of Spectrochemical Analysis and Instrumentation, and Innovation Center for Cell Signaling Network, and ‡State Key Laboratory of Cellular Stress Biology, Innovation Center for Cell Signaling Network, School of Life Sciences, Xiamen University, Xiamen, 361005, China.
authors.forename: Xuanjun
authors.initials: X
authors.lastname: Wu
authors.affiliation: †Department of Chemical Biology, College of Chemistry and Chemical Engineering, State Key Laboratory for Physical Chemistry of Solid Surfaces, the Key Laboratory for Chemical Biology of Fujian Province, the MOE Key Laboratory of Spectrochemical Analysis and Instrumentation, and Innovation Center for Cell Signaling Network, and ‡State Key Laboratory of Cellular Stress Biology, Innovation Center for Cell Signaling Network, School of Life Sciences, Xiamen University, Xiamen, 361005, China.
authors.forename: Bijuan
authors.initials: B
authors.lastname: Lin
authors.affiliation: †Department of Chemical Biology, College of Chemistry and Chemical Engineering, State Key Laboratory for Physical Chemistry of Solid Surfaces, the Key Laboratory for Chemical Biology of Fujian Province, the MOE Key Laboratory of Spectrochemical Analysis and Instrumentation, and Innovation Center for Cell Signaling Network, and ‡State Key Laboratory of Cellular Stress Biology, Innovation Center for Cell Signaling Network, School of Life Sciences, Xiamen University, Xiamen, 361005, China.
authors.forename: Jiahuai
authors.initials: J
authors.lastname: Han
authors.affiliation: †Department of Chemical Biology, College of Chemistry and Chemical Engineering, State Key Laboratory for Physical Chemistry of Solid Surfaces, the Key Laboratory for Chemical Biology of Fujian Province, the MOE Key Laboratory of Spectrochemical Analysis and Instrumentation, and Innovation Center for Cell Signaling Network, and ‡State Key Laboratory of Cellular Stress Biology, Innovation Center for Cell Signaling Network, School of Life Sciences, Xiamen University, Xiamen, 361005, China.
authors.forename: Liu
authors.initials: L
authors.lastname: Yang
authors.affiliation: †Department of Chemical Biology, College of Chemistry and Chemical Engineering, State Key Laboratory for Physical Chemistry of Solid Surfaces, the Key Laboratory for Chemical Biology of Fujian Province, the MOE Key Laboratory of Spectrochemical Analysis and Instrumentation, and Innovation Center for Cell Signaling Network, and ‡State Key Laboratory of Cellular Stress Biology, Innovation Center for Cell Signaling Network, School of Life Sciences, Xiamen University, Xiamen, 361005, China.
authors.forename: Shoufa
authors.initials: S
authors.lastname: Han
mesh_terms: D005456:Fluorescent Dyes / Q000378:metabolism*; D006863:Hydrogen-Ion Concentration; D007249:Inflammation / Q000378:metabolism*; D008247:Lysosomes / Q000378:metabolism*; D019158:N-Acetylneuraminic Acid / Q000378:metabolism*
chemical_list: D005456:Fluorescent Dyes; D019158:N-Acetylneuraminic Acid