Elucidation of intracellular uptake and degradation mechanism of photosensitizer talaporfin. (12th August 2020)

• Record Type: Journal Article
• Authors: Saito, Takuma; Tsukahara, Tomohide; Kubo, Terufumi; Kanaseki, Takayuki; Hirohashi, Yoshihiko; Torigoe, Toshihiko; Li, Liming
• Is Part Of: Molecular crystals and liquid crystals. Volume 707(2020)
• Page Start: 81
• Page End: 87
• Publication Date: 2020-08-12
• Subjects: Endocytosis -- photodynamic diagnosis -- photodynamic therapy -- talaporfin; Molecular crystals -- Periodicals; Liquid crystals -- Periodicals; Liquid crystals; Molecular crystals; Periodicals; 548
• DOI: 10.1080/15421406.2020.1743458
• Languages: English
• ISSNs: 1542-1406

Abstract

Abstract: The photosensitizer talaporfin has been widely used in photodynamic therapy (PDT), but the mechanism of uptake and excretion has not been identified yet. We do research on the metabolism of talaporfin, i.e., endocytotic uptake and lysosomal degradation. Subcellular localization of talaporfin and lysosome were investigated to certify involvement of endocytosis. Talaporfin was introduced into cell lines transfected with lysosomal-associated membrane protein one Green fluorescent protein (LAMP1-GFP). The localization of fluorescence in cells was analyzed by a confocal fluorescence microscope. The fluorescence of talaporfin matched with LAMP1. Six inhibitors were used to inhibit the uptake of talaporfin in order to identify the endocytosis uptake pathway. It is suggested that clathrin and caveolae endocytosis are involved in talaporfin uptake. To investigate lysosomal degradation, talaporfin was taken up for 1 h and then NH4 Cl or Chloroquine (CQ) was added to evaluate the decrease in fluorescence intensity of the cells, and it was clearly shown that CQ inhibited talaporfin degradation. These results lead to the conclusion that talaporfin was taken up into tumor cells by endocytosis and degraded by lysosome.