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Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1990 Apr;87(8):2980–2984. doi: 10.1073/pnas.87.8.2980

Readily available fluorescein isothiocyanate-conjugated antibodies can be easily converted into targeted phototoxic agents for antibacterial, antiviral, and anticancer therapy.

S Devanathan 1, T A Dahl 1, W R Midden 1, D C Neckers 1
PMCID: PMC53817  PMID: 2109321

Abstract

Fluorescein-labeled antibodies have little, if any, photodynamic effect because energy acquired by light absorption is rapidly dissipated in fluorescence. However, they can be easily and efficiently converted to selective photodynamic sensitizers by iodination under mild conditions. We have outlined general experimental procedures that can be used to turn a fluorescein-labeled anti-Escherichia coli antibody into a photodynamic sensitizer that selectively kills E. coli while sparing closely related Salmonella typhimurium. These results demonstrate that iodination did not destroy the specificity or activity of the antibody. This technique should be applicable to the large number of fluoresceinated antibodies that are commercially available. Thus, this strategy provides a simple way to rapidly prepare a large number of targeted phototoxic agents that can be used for the selective destruction with light of nearly any type of tissue or organism.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Banks J. G., Board R. G., Carter J., Dodge A. D. The cytotoxic and photodynamic inactivation of micro-organisms by Rose Bengal. J Appl Bacteriol. 1985 Apr;58(4):391–400. doi: 10.1111/j.1365-2672.1985.tb01478.x. [DOI] [PubMed] [Google Scholar]
  2. Bertoloni G., Salvato B., Dall'Acqua M., Vazzoler M., Jori G. Hematoporphyrin-sensitized photoinactivation of Streptococcus faecalis. Photochem Photobiol. 1984 Jun;39(6):811–816. doi: 10.1111/j.1751-1097.1984.tb08864.x. [DOI] [PubMed] [Google Scholar]
  3. Blair A. H., Ghose T. I. Linkage of cytotoxic agents to immunoglobulins. J Immunol Methods. 1983 Apr 29;59(2):129–143. doi: 10.1016/0022-1759(83)90024-8. [DOI] [PubMed] [Google Scholar]
  4. Dahl T. A., Midden W. R., Hartman P. E. Comparison of killing of gram-negative and gram-positive bacteria by pure singlet oxygen. J Bacteriol. 1989 Apr;171(4):2188–2194. doi: 10.1128/jb.171.4.2188-2194.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Dahl T. A., Midden W. R., Hartman P. E. Pure exogenous singlet oxygen: nonmutagenicity in bacteria. Mutat Res. 1988 Sep;201(1):127–136. doi: 10.1016/0027-5107(88)90119-4. [DOI] [PubMed] [Google Scholar]
  6. Dahl T. A., Midden W. R., Hartman P. E. Pure singlet oxygen cytotoxicity for bacteria. Photochem Photobiol. 1987 Sep;46(3):345–352. doi: 10.1111/j.1751-1097.1987.tb04779.x. [DOI] [PubMed] [Google Scholar]
  7. Dahl T. A., Midden W. R., Hartman P. E. Some prevalent biomolecules as defenses against singlet oxygen damage. Photochem Photobiol. 1988 Mar;47(3):357–362. doi: 10.1111/j.1751-1097.1988.tb02737.x. [DOI] [PubMed] [Google Scholar]
  8. Dahl T. A., Midden W. R., Neckers D. C. Comparison of photodynamic action by Rose Bengal in gram-positive and gram-negative bacteria. Photochem Photobiol. 1988 Nov;48(5):607–612. doi: 10.1111/j.1751-1097.1988.tb02870.x. [DOI] [PubMed] [Google Scholar]
  9. Ito T. Cellular and subcellular mechanisms of photodynamic action: the 1O2 hypothesis as a driving force in recent research. Photochem Photobiol. 1978 Oct-Nov;28(4-5):493–508. doi: 10.1111/j.1751-1097.1978.tb06957.x. [DOI] [PubMed] [Google Scholar]
  10. JOHNSON A., DAY E. D., PRESSMAN D. The effect of iodination on antibody activity. J Immunol. 1960 Feb;84:213–220. [PubMed] [Google Scholar]
  11. LOWRY O. H., ROSEBROUGH N. J., FARR A. L., RANDALL R. J. Protein measurement with the Folin phenol reagent. J Biol Chem. 1951 Nov;193(1):265–275. [PubMed] [Google Scholar]
  12. Mew D., Wat C. K., Towers G. H., Levy J. G. Photoimmunotherapy: treatment of animal tumors with tumor-specific monoclonal antibody-hematoporphyrin conjugates. J Immunol. 1983 Mar;130(3):1473–1477. [PubMed] [Google Scholar]
  13. Oseroff A. R., Ohuoha D., Hasan T., Bommer J. C., Yarmush M. L. Antibody-targeted photolysis: selective photodestruction of human T-cell leukemia cells using monoclonal antibody-chlorin e6 conjugates. Proc Natl Acad Sci U S A. 1986 Nov;83(22):8744–8748. doi: 10.1073/pnas.83.22.8744. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Pooler J. P., Valenzeno D. P. Physicochemical determinants of the sensitizing effectiveness for photooxidation of nerve membranes by fluorescein derivatives. Photochem Photobiol. 1979 Oct;30(4):491–498. doi: 10.1111/j.1751-1097.1979.tb07168.x. [DOI] [PubMed] [Google Scholar]
  15. Thorpe P. E., Ross W. C. The preparation and cytotoxic properties of antibody-toxin conjugates. Immunol Rev. 1982;62:119–158. doi: 10.1111/j.1600-065x.1982.tb00392.x. [DOI] [PubMed] [Google Scholar]
  16. Vitetta E. S., Krolick K. A., Uhr J. W. Neoplastic B cells as targets for antibody-ricin A chain immunotoxins. Immunol Rev. 1982;62:159–183. doi: 10.1111/j.1600-065x.1982.tb00393.x. [DOI] [PubMed] [Google Scholar]

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