title: Metabolism-Based Click-Mediated Platform for Specific Imaging and Quantification of Cell Surface Sialic Acids.
abstract: Although we believe that the cell surface sialic acids (Sias) are playing an important role in cell-cell interactions and related tumor metastasis processes, acquisition of their quantitative information has yet been a challenge to date. Here, we reported the construction of a new analytical platform for Sias-specific imaging and quantification. We used N-azidoacetyl-mannosamine tetraacylated as a metabolic sugar substrate to bioassemble azido-Sias on the surface of cells via the metabolic pathway of Sias de novo synthesis. These azido-Sias allow us to perform a duplex Sias-specific analysis with various fluorescent and elemental reporters such as DIBO-Alexa Fluor 647, DBCO-DOTA-Eu, and DBCO-PEG4-BODIPY, which can be easily labeled and/or tagged through an effective copper-free bioorthogonal click reaction. Compared to the previous reported strategies, we quantified the cell surface Sias with the LODs (3σ) down to 8.9 fmol and 0.24 pmol using153Eu- and10B-species unspecific isotope dilution ICPMS, in addition to their red- and green-CLSM profiling. Such a platform enables us to evaluate Sias regulation under the administration of paclitaxel, finding that 1 μM paclitaxel induced a significant Sias decrease of 67% on the surface of hepatic tumor cell SMMC-7721, while had no obvious adverse effect to that of para-carcinomatous liver cell LO2. Besides Sias, we believe that this metabolism-based click-mediated platform will provide opportunities to study other monosaccharides and their corresponding biological roles when more corresponding chemically modified sugar substrates and specific bioorthogonal reactions are developed.
authors.affiliation: Department of Chemistry & the MOE Key Lab of Spectrochemical Analysis and Instrumentation, College of Chemistry and Chemical Engineering, Xiamen University , Xiamen 361005, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Liang
authors.affiliation: School of Pharmaceutical Sciences, Xiamen University , Xiamen 361005, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Jiang
authors.affiliation: Department of Chemistry & the MOE Key Lab of Spectrochemical Analysis and Instrumentation, College of Chemistry and Chemical Engineering, Xiamen University , Xiamen 361005, China.
authors.forename: Rong
authors.initials: R
authors.lastname: Yuan
authors.affiliation: Department of Chemistry & the MOE Key Lab of Spectrochemical Analysis and Instrumentation, College of Chemistry and Chemical Engineering, Xiamen University , Xiamen 361005, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: Department of Chemistry & the MOE Key Lab of Spectrochemical Analysis and Instrumentation, College of Chemistry and Chemical Engineering, Xiamen University , Xiamen 361005, China.
authors.forename: Caixia
authors.initials: C
authors.lastname: Ji
authors.affiliation: Department of Chemistry & the MOE Key Lab of Spectrochemical Analysis and Instrumentation, College of Chemistry and Chemical Engineering, Xiamen University , Xiamen 361005, China.
authors.forename: Limin
authors.initials: L
authors.lastname: Yang
authors.affiliation: School of Pharmaceutical Sciences, Xiamen University , Xiamen 361005, China.
authors.forename: Haifeng
authors.initials: H
authors.lastname: Chen
authors.affiliation: Department of Chemistry & the MOE Key Lab of Spectrochemical Analysis and Instrumentation, College of Chemistry and Chemical Engineering, Xiamen University , Xiamen 361005, China.|State Key Lab of Marine Environmental Science, Xiamen University , Xiamen 361005, China.
authors.forename: Qiuquan
authors.identifier: 0000-0002-5166-4048
authors.initials: Q
authors.lastname: Wang
mesh_terms: D001386:Azides / Q000737:chemistry; D001896:Boron Compounds / Q000737:chemistry; D045744:Cell Line, Tumor; D057930:Click Chemistry; D006801:Humans; D055432:Metabolomics / Q000379:methods*; D057054:Molecular Imaging / Q000379:methods*; D012794:Sialic Acids / Q000737:chemistry / Q000378:metabolism*; D013499:Surface Properties
chemical_list: C095489:4,4-difluoro-4-bora-3a,4a-diaza-s-indacene; D001386:Azides; D001896:Boron Compounds; D012794:Sialic Acids