This title appears in the Scientific Report :
2020
Please use the identifier:
http://dx.doi.org/10.1021/acs.biomac.0c01216 in citations.
Azulitox—A Pseudomonas aeruginosa P28-Derived Cancer-Cell-Specific Protein Photosensitizer
Azulitox—A Pseudomonas aeruginosa P28-Derived Cancer-Cell-Specific Protein Photosensitizer
Azulitox as a new fusion polypeptide with cancer cell specificity and phototoxicity was generated and is composed of a photosensitizer domain and the cell-penetrating peptide P28. The photosensitizer domain (EcFbFP) was derived from a bacterial blue-light receptor, which belongs to the family of lig...
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Personal Name(s): | Raber, Heinz Fabian |
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Heerde, Thomas / El Din, Suzanne Nour / Flaig, Carolin / Hilgers, Fabienne / Bitzenhofer, Nora / Drepper, Thomas / Gottschalk, Kay-Eberhard / Bodenberger, Nicholas Emil / Weil, Tanja / Kubiczek, Dennis Horst (Corresponding author) / Rosenau, Frank / Jaeger, Karl-Erich | |
Contributing Institute: |
Institut für Molekulare Enzymtechnologie (HHUD); IMET |
Published in: | Biomacromolecules, 21 (2020) 12, S. 5067–5076 |
Imprint: |
Columbus, Ohio
American Chemical Soc.
2020
|
DOI: |
10.1021/acs.biomac.0c01216 |
Document Type: |
Journal Article |
Research Program: |
Biotechnology |
Publikationsportal JuSER |
Azulitox as a new fusion polypeptide with cancer cell specificity and phototoxicity was generated and is composed of a photosensitizer domain and the cell-penetrating peptide P28. The photosensitizer domain (EcFbFP) was derived from a bacterial blue-light receptor, which belongs to the family of light-oxygen-voltage proteins and produces reactive oxygen species (ROS) upon excitation. P28 is derived from the cupredoxin protein azurin that is known to specifically penetrate cancer cells and bind to the tumor suppressor protein p53. We show that the P28 domain specifically directs and translocates the fused photosensitizer into cancer cells. Under blue-light illumination, Azulitox significantly induced cytotoxicity. Compared to the extracellular application of EcFbFP, Azulitox caused death to about 90% of cells, as monitored by flow cytometry, which also directly correlated with the amount of ROS produced in the cells. Azulitox may open new avenues toward targeted polypeptide–photosensitizer-based photodynamic therapies with reduced systemic toxicity compared to conventional photosensitizers. |