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Noninvasive monitoring of intracellular pH change induced by drug stimulation using silica nanoparticle sensors

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Abstract

We have synthesized and applied a nanoparticle-based pH sensor for noninvasive monitoring of intracellular pH changes induced by drug stimulation. The pH sensor is a two-fluorophore-doped nanoparticle sensor (2DFNS) that contains a pH-sensitive indicator (fluorescein isothiocyanate, FITC) and a reference dye (tris(2,2′-bipyridyl)dichlororuthenium(II) hexahydrate, RuBPY). The nanoparticles have an average diameter of 42 ± 3 nm and can easily be taken up by cells for noninvasive intracellular pH measurement. The 2DFNS exhibited excellent pH sensitivity, reversibility, and a dynamic range of pH 4–7 for biological studies. We have used 2DFNS to monitor pH changes in living cells by drug stimulation. Both lysosomal pH changes in murine macrophages stimulated by chloroquine and intracellular acidification in apoptotic cancer cells were monitored in real time and with high pH sensitivity. Hela cells underwent intracellular acidification with a drop in pH from 7.2 to 6.5 after 8 h of treatment with 2 μmol/L dexamethasone, and this intracellular pH drop in the apoptotic cells was not influenced by the addition of zinc ions. The application of 2DFNS to intracellular pH measurements yields some important advantages: excellent pH sensitivity, little environmental effect on the pH dye, excellent quantification, high stability and excellent reversibility.

Scanning images of macrophages loaded with 2DFNS at different times after exposure to 200 μmol/L chloroquine. Images a and b represent fluorescence images of FITC and RuBPY in 2DFNS internalized by a macrophage, respectively. Images labeled c are bright-field images of the macrophage, and those labeled d show a and b merged

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Acknowledgements

This work was partially supported by the National Key Basic Research Program (2002CB513100-10), Key Project Foundation of China Education Ministry (107084), Key Project of International Technologies Collaboration Program of China (2003DF000039), Program for New Century Excellent Talents in University (NCET), National Science Foundation of P.R.China (90606003, 20405005) and Outstanding Youth Foundation of Hunan Province (06JJ10004).

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Authors and Affiliations

  1. Biomedical Engineering Center, State Key Laboratory of Chemo/Biosensing and Chemometrics, College of Chemistry and Chemical Engineering, Hunan University, Changsha, 410082, China

    Jiaofeng Peng, Xiaoxiao He, Kemin Wang, Weihong Tan, Yan Wang & Yi Liu

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  1. Jiaofeng Peng
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  2. Xiaoxiao He
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  3. Kemin Wang
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  4. Weihong Tan
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  5. Yan Wang
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Correspondence to Kemin Wang.

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Peng, J., He, X., Wang, K. et al. Noninvasive monitoring of intracellular pH change induced by drug stimulation using silica nanoparticle sensors. Anal Bioanal Chem 388, 645–654 (2007). https://doi.org/10.1007/s00216-007-1244-9

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  • DOI: https://doi.org/10.1007/s00216-007-1244-9

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