Cellular and Antitumor Activity of a New Diethylene Glycol Benzoporphyrin Derivative (Lemuteporfin)

A newly synthesized diethylene glycol functionalized chlorin-type photosensitizer, lemuteporfin, was characterized for use in photodynamic therapy (PDT) in a panel of in vitro and in vivo test systems. The photosensitizer was highly potent, killing cells at low nanomolar concentrations upon exposure...

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Published in:Photochemistry and photobiology 2006-01, Vol.82 (1), p.219-224
Main Authors: Boch, Ron, Canaan, Alice J., Cho, Angela, Dolphin, David D., Hong, Lina, Jain, Ashok K., North, John R., Richter, Anna M., Smits, Claire, Sternberg, Ethan D.
Format: Article
Language:English
Subjects:
Animals
Antineoplastic Agents - chemistry
Antineoplastic Agents - toxicity
Cell Survival - drug effects
Ethylene Glycols - chemistry
Ethylene Glycols - toxicity
Hematoporphyrins
J. C. (Tito) Scaiano Honorary Issue
Leukemia L1210 - pathology
Mice
Photochemotherapy
Porphyrins - chemistry
Porphyrins - toxicity
Spectrophotometry
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Summary:A newly synthesized diethylene glycol functionalized chlorin-type photosensitizer, lemuteporfin, was characterized for use in photodynamic therapy (PDT) in a panel of in vitro and in vivo test systems. The photosensitizer was highly potent, killing cells at low nanomolar concentrations upon exposure to activating light. The cellular uptake of lemuteporfin was rapid, with maximum levels reached within 20 min. Mitogen-activated lymphoid cells accumulated more of the lemuteporfin than their quiescent equivalents, supporting selectivity. Photosensitizer fluorescence in the skin increased rapidly within the first few minutes following intravenous administration to mice, then decreased over the next 24 h. Skin photosensitivity reactions indicated rapid clearance of the photosensitizer. Intravenous doses as low as 1.4 μmol/kg combined with exposure to 50 J/cm2 red light suppressed tumor growth in a mouse model. In conclusion, this new benzoporphyrin was found to be an effective photosensitizer, showing rapid uptake and clearance both in vitro and in vivo. This rapid photosensitization of tumors could be useful in therapies requiring a potent, rapidly accumulating photosensitizer, while minimizing the potential for skin photosensitivity reactions to sunlight following treatment.
ISSN:0031-8655
1751-1097
DOI:10.1562/2005-06-03-RA-564