A series of naphthalimide derivatives as intra and extracellular pH sensors

Yanqing Tian, Fengyu Su, Warner Weber, Vivek Nandakumar, Bradley R. Shumway, Yuguang Jin, Xianfeng Zhou, Mark R. Holl, Roger H. Johnson, Deirdre Meldrum

Research output: Contribution to journalArticle

93 Citations (Scopus)

Abstract

A series of new naphthalimide derivatives were synthesized and studied. Three of the materials (SM1, SM2, and SM3) possess methacrylate(s) moieties as pH sensor monomers, enabling these compounds to be polymerized with other monomers for thin film preparation for extracellular pH sensing. Herein, poly(2-hydroxyethyl methacrylate)-co-poly(acrylamide) (PHEMA-co-PAM) was chosen as the polymer matrix. Structure influences on pH responses and pKa values were studied. The film P3 composed of the sensing moiety SM3 has a pKa close to the usual biological environmental pH of ∼7. It was used as an extracellular pH sensor to monitor pH change during the metabolism of prokaryotic Escherichia coli (E. coil). On the other hand, the three sensor monomers are new intracellular biomarkers to sense lysosomes of eukaryotic cells since (1) their pKa values are in a range of 5.9-6.8; (2) their emission intensities at acidic conditions (such as at pH 5) are much stronger than those at a neutral condition of pH 7; (3) lysosomes range in size from 0.1 to 1.2 μm in diameter with pH ranging from 4.5 to 5.0, which is much more acidic than the pH value of the cytoplasm (usually with a pH value of ∼7.2); and (4) the acidity of lysosomes enables a protonation of the amino groups of the pH probes making the sensors emit brightly in acidic organelles by inhibiting the photo-induced electron transfer from the amino groups to the fluorophores. Lysosome sensing was demonstrated using live human brain glioblastoma U87MG cell line, human cervical cancer HeLa cell line, and human esophagus premalignant CP-A and CP-D cell lines by observations of small acidic spherical organelles (lysosomes) and significant colocalizations (82-95%) of the sensors with a commercially available lysosome-selective staining probe LysoTracker Red® under confocal fluorescence microscopy.

Original languageEnglish (US)
Pages (from-to)7411-7422
Number of pages12
JournalBiomaterials
Volume31
Issue number29
DOIs
StatePublished - Oct 2010

Fingerprint

Naphthalimides
pH sensors
Monomers
Cells
Derivatives
Sensors
Lysosomes
Film preparation
Methacrylates
Fluorophores
Confocal microscopy
Fluorescence microscopy
Protonation
Biomarkers
Polyacrylates
Polymer matrix
Metabolism
Acidity
Escherichia coli
Brain

Keywords

  • Extracellular sensing
  • Intracellular pH sensing
  • Lysosome sensor
  • Naphthalimide derivatives
  • Optical sensors
  • PH sensor

ASJC Scopus subject areas

  • Biomaterials
  • Bioengineering
  • Ceramics and Composites
  • Mechanics of Materials
  • Biophysics

Cite this

A series of naphthalimide derivatives as intra and extracellular pH sensors. / Tian, Yanqing; Su, Fengyu; Weber, Warner; Nandakumar, Vivek; Shumway, Bradley R.; Jin, Yuguang; Zhou, Xianfeng; Holl, Mark R.; Johnson, Roger H.; Meldrum, Deirdre.

In: Biomaterials, Vol. 31, No. 29, 10.2010, p. 7411-7422.

Research output: Contribution to journalArticle

Tian, Y, Su, F, Weber, W, Nandakumar, V, Shumway, BR, Jin, Y, Zhou, X, Holl, MR, Johnson, RH & Meldrum, D 2010, 'A series of naphthalimide derivatives as intra and extracellular pH sensors', Biomaterials, vol. 31, no. 29, pp. 7411-7422. https://doi.org/10.1016/j.biomaterials.2010.06.023
Tian Y, Su F, Weber W, Nandakumar V, Shumway BR, Jin Y et al. A series of naphthalimide derivatives as intra and extracellular pH sensors. Biomaterials. 2010 Oct;31(29):7411-7422. https://doi.org/10.1016/j.biomaterials.2010.06.023
Tian, Yanqing ; Su, Fengyu ; Weber, Warner ; Nandakumar, Vivek ; Shumway, Bradley R. ; Jin, Yuguang ; Zhou, Xianfeng ; Holl, Mark R. ; Johnson, Roger H. ; Meldrum, Deirdre. / A series of naphthalimide derivatives as intra and extracellular pH sensors. In: Biomaterials. 2010 ; Vol. 31, No. 29. pp. 7411-7422.
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