Synthesis of A Sulfonamide-Substituted Benzothiadiazole-Based Fluorescent Dye and Study of Its Application for Long-Term Cancer Cell Tracking

doi:10.6023/cjoc202202037

Abstract

To develop long-term cancer cell tracking dyes with anti-photobleaching, large Stokes shift, and excellent biocompatibility is the research hotspot in the field of biological imaging. In this study, a donor-acceptor-donor (D-A-D) stuctured benzothiadiazole (BTD)-based fluorescent dye was sythesized, namely SIBIS. The BTD with excellent optical properties was chosen as the core stucture and the N,N-dimethyl substituted sulfonamide was selceted to improve the biocompatibility and solubility of fluorescent dye. SIBIS possessed aggregation-induced emission (AIE), large Stokes shift (155 nm) and low cytotoxicity. The endocytosis results in different cell lines showed that SIBIS could target lysosome of living cells. The long-term 4T1 cell tracking results showed that SIBIS could effectively trace cell divisions for more than 15 generations. Therefore, SIBIS can serve as a kind of promising long-term cell traking agents tumor cells, and has a great potential for further biological applications for tracking various kinds of lysosomal related inflammation and diseases.

Key words: long-term cancer cell tracking, benzothiadiazole, N,N-dimethyl substituted sulfonamide, aggregation-induced emission

Cite this article

Weikang Xia, Chuang Liu, Sheng Ye, Lei Wang, Ruiyuan Liu. Synthesis of A Sulfonamide-Substituted Benzothiadiazole-Based Fluorescent Dye and Study of Its Application for Long-Term Cancer Cell Tracking[J]. Chinese Journal of Organic Chemistry, 2022, 42(8): 2535-2541.

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Fig. & Tab. 6

Scheme 1. Synthetic route of SIBIS

Figure 1. (a) UV-vis absorption spectra of SIBIS in different solvents; (b) FL spectra of SIBIS in different solvents; (c) UV-vis absorption spectra of SIBIS in the DMSO/water mixtures with different water fractions (fw); (d) FL spectra of SIBIS in the DMSO/water mixtures with different water fractions (fw)

Figure 2. Cell viabilities of cell lines including 4T1 cells, HeLa cells, and MCF-7 cells co-stained with different SIBIS concentrations

Figure 3. CLSM images of cells lines including 4T1 cells, HeLa cells, MCF-7 cells after incubation with SIBIS (0.5 μmol/L, 6 h) and Lyso-Tracker Red (100 nmol/L, 0.5 h) in sequence (sale bar: 10 μm)

Figure 4. CLSM images of 4T1 cells co-stained with SIBIS (0.5 μmol/L) at different generations (scale bar: 10 μm)

Figure 5. Flow cytometry profiles of SIBIS co-stained 4T1 cells at different generations

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