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Cell‐specific Retention and Action of Pheophorbide‐based Photosensitizers in Human Lung Cancer Cells
Author(s) -
Tracy Erin C.,
Bowman MaryJo,
Pandey Ravendra K.,
Baumann Heinz
Publication year - 2018
Publication title -
photochemistry and photobiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.818
H-Index - 131
eISSN - 1751-1097
pISSN - 0031-8655
DOI - 10.1111/php.13043
Subject(s) - chemistry , photosensitizer , pheophorbide a , in vivo , in vitro , photodynamic therapy , cancer research , cell , cancer cell , porphyrin , biochemistry , cancer , biology , medicine , photochemistry , microbiology and biotechnology , organic chemistry
This study determined in primary cultures of human lung cancer cells the cell specificity of chlorin‐based photosensitizers. Epithelial cells (ECs) preferentially retained 3‐[1‐hexyloxyethyl]‐2‐devinylpyropheophorbide‐a ( HPPH ) and related structural variants. Tumor‐associated fibroblasts (Fb) differ from EC by a higher efflux rate of HPPH . Immunoblot analyses indicated dimerization of STAT 3 as a reliable biomarker of the photoreaction. Compared to mitochondria/ ER ‐localized photoreaction by HPPH , the photoreaction by lysosomally targeted HPPH ‐lactose showed a trend toward lower STAT 3 cross‐linking. Lethal consequence of the photoreaction differed between EC and Fb with the latter cells being more resistant. A survey of lung tumor cases indicated a large quantitative range by which EC retains HPPH . The specificity of HPPH retention defined in vitro could be confirmed in vivo in selected cases grown as xenografts. HPPH retention as a function of the tetrapyrrole structure was evaluated by altering side groups on the porphyrin macrocycle. The presence or absence of a carboxylic acid at position 17 2 proved to be critical. A benzyl group at position 20 enhanced retention in a subset of cancer cells with low HPPH binding. This study indicated experimental tools that are potentially effective in defining the photosensitizer preference and application for individual patient's cancer lesions.