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A series of naphthalimide derivatives as intra and extracellular pH sensors. Biomaterials 2010 Oct;31(29):7411-22

Date

07/14/2010

Pubmed ID

20619451

Pubmed Central ID

PMC2940253

DOI

10.1016/j.biomaterials.2010.06.023

Scopus ID

2-s2.0-77955276024   100 Citations

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 pK(a) values were studied. The film P3 composed of the sensing moiety SM3 has a pK(a) close to the usual biological environmental pH of approximately 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 pK(a) 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 mum 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 approximately 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.

Author List

Tian Y, Su F, Weber W, Nandakumar V, Shumway BR, Jin Y, Zhou X, Holl MR, Johnson RH, Meldrum DR

Author

Roger H. Johnson PhD Associate Professor in the Biophysics department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Cell Line, Tumor
HeLa Cells
Humans
Hydrogen-Ion Concentration
Models, Theoretical
Naphthalimides
Optical Devices