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A SERS/fluorescence dual-mode immuno-nanoprobe for investigating two anti-diabetic drugs on EGFR expressions

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Abstract

A surface-enhanced Raman scattering (SERS)/fluorescence dual-mode nanoprobe was proposed to assess anti-diabetic drug actions from the expression level of the epidermal growth factor receptor (EGFR), which is a significant biomarker of breast cancers. The nanoprobe has a raspberry shape, prepared by coating a dye-doped silica nanosphere with a mass of SERS tags, which gives high gains in fluorescence imaging and SERS measurement. The in situ detection of EGFR on the cell membrane surfaces after drug actions was achieved by using this nanoprobe, and the detection results agree with the enzyme-linked immunosorbent assay (ELISA) kit. Our study suggests that rosiglitazone hydrochloride (RH) may be a potential drug for diabetic patients with breast cancer, while the anti-cancer effect of metformin hydrochloride (MH) is debatable since MH slightly promotes the EGFR expression of MCF-7 cells in this study. This sensing platform endows more feasibility for highly sensitive and accurate feedback of pesticide effects at the membrane protein level.

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Funding

This work was supported by the National Natural Science Foundation of China (NSFC) (Nos. 21873039, 22173035, and 21827805), Technology Development Program of Jilin Province (20220101046JC), Department of Finance of Jilin Province (2021CSZ14), Opening Project of State Key Laboratory of Applied Optics (SKLAO2021001A14), and Interdisciplinary Integration Innovation Project of Jilin University (JLUXKJC2020106).

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Authors and Affiliations

  1. State Key Laboratory of Supramolecular Structure and Materials, College of Chemistry, Jilin University, Changchun, 130012, People’s Republic of China

    Yuqi Cheng, Lili Cong, Junyi Zhao, Jiamin Chen, Weiqing Xu & Shuping Xu

  2. Institute of Theoretical Chemistry, College of Chemistry, Jilin University, Changchun, 130012, People’s Republic of China

    Yuqi Cheng, Junyi Zhao, Jiamin Chen, Weiqing Xu & Shuping Xu

  3. The First Hospital of Jilin University, Changchun, 130031, People’s Republic of China

    Xiaozhang Qu

  4. Rheumatology and Immunology Department, China-Japan Union Hospital of Jilin University, Changchun, 130033, People’s Republic of China

    Ping Li

  5. Key Lab for Molecular Enzymology & Engineering of Ministry of Education, Jilin University, Changchun, 130012, People’s Republic of China

    Wei Shi

  6. Center for Supramolecular Chemical Biology, College of Chemistry, Jilin University, Changchun, 130012, People’s Republic of China

    Shuping Xu

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  1. Yuqi Cheng
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Contributions

Yuqi Cheng: conceptualization, data curation, formal analysis, writing—original draft. Lili Cong: conceptualization, writing—review and editing. Xiaozhang Qu: conceptualization, methodology, investigation. Junyi Zhao: formal analysis. Jiamin Chen: investigation. Ping Li: funding acquisition. Wei Shi: methodology. Weiqing Xu: conceptualization, supervision, funding acquisition, project administration. Shuping Xu: conceptualization, writing—review and editing, supervision, funding acquisition, project administration.

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Correspondence to Ping Li or Shuping Xu.

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Supplementary materials

Supplementary materials 1:

Figure S1 UV-vis spectra of FITC and F-SiO2. Figure S2 The average particles diameter of F-SiO2 (n=150). Figure S3 TEM image of F-SiO2-Au/Ag. Scale bar: 200 nm. Figure S4 Optimization of the concentration of AgNO3 for preparing F-SiO2-Au/Ag NPs and their SERS activity. SERS spectra (a) and the response histogram (b) at 1073 cm-1 of MBA modified F-SiO2-Au/Ag nanoprobes obtained by different concentrations of AgNO3 (200, 300, 400, and 500 μM, respectively). Figure S5 Confocal laser scanning microscope (CLSM) images of F-SiO2-Au/Ag nanoprobes obtained by different concentrations of AgNO3 200, 300, 400, and 500 μM (a-d), respectively. Scale bar: 200 μm. Figure S6 Fluorescence images (a) and Raman spectra (b) of MCF-7 cells incubated with F-SiO2-Au/Ag-MBA (0.06 mg/mL). Scale bar: 200 μm. Figure S7 CLSM images of MCF-7 cells treated with/without MH (20 and 40 mM) and RH (100 μM). Scale bar: 50 μm. Figure S8 (a) CLSM images of MCF-7 cells treated with MH (40 mM). Scale bar: 50 μm. (b) t-Test analysis of the mean intensity of EGFR from each cell. 210 cells are processed with ImageJ software. The error bars represent the standard deviations of mean intensity. **** means significantly different at the p-value < 0.0001. (c) Heatmap of fluorescent intensity. Figure S9 (a) Schematic representation of the constructed model. FDTD simulation of the electronic field distributions of (b) the closely packed Ag NPs on a single F-SiO2 NSs (c) and (d) two adjacent F-SiO2-Au/Ag NPs. Figure S10 Control Raman spectra (a) and SERS spectra (b) of 4-MBA. Figure S11 (a) The average SERS spectra of MBA obtained from MCF-7 cell membranes after they were treated with/without MH (40 mM). (b) t-Test analysis of the Raman intensity at 1073 cm-1 from 50 cells. **** means p-value < 0.0001. (c) Heatmap of SERS intensity. Figure S12 The ELISA kit results of the EGFR/TGF-α expression of MCF-7 cells with/without MH (40 mM). (a) The calculated concentrations of EGFR. (b) The calculated concentrations of TGF-α.

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Cheng, Y., Cong, L., Qu, X. et al. A SERS/fluorescence dual-mode immuno-nanoprobe for investigating two anti-diabetic drugs on EGFR expressions. Microchim Acta 190, 124 (2023). https://doi.org/10.1007/s00604-023-05705-2

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