Uptake kinetics and intracellular localization of hypocrellin photosensitizers for photodynamic therapy: a confocal microscopy study.
Hypocrellins are naturally occurring compounds with photosensitizing properties in biological systems. We have prepared synthetic derivatives of hypocrellin B, which have promise as photosensitizers in the clinical application of photodynamic therapy. The intracellular localization and uptake kinetics of hypocrellin B and several selected hypocrellin congeners were determined semiquantitatively by fluorescence confocal microscopy in monolayer cultures of EMT6/Ed murine tumor cells. Each compound had unique uptake kinetics. Although no compound tested to date has demonstrated nuclear labeling, most could be detected in lysosomes, Golgi, endoplasmic reticulum and, to a minor extent, in cellular membranes. No two compounds gave identical labeling distributions. The differences are assumed to originate in physicochemical properties characteristic of each compound, which may ultimately impact upon the primary modality of phototoxicity.
Miller
G G
GG
Department of Surgery, Cross Cancer Institute, Edmonton, Alberta, Canada.
Brown
K
K
Moore
R B
RB
Diwu
Z J
ZJ
Liu
J
J
Huang
L
L
Lown
J W
JW
Begg
D A
DA
Chlumecky
V
V
Tulip
J
J
D000818:Animals; D007424:Intracellular Fluid / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D018613:Microscopy, Confocal / Q000379:methods; D008856:Microscopy, Fluorescence / Q000379:methods; D009368:Neoplasm Transplantation; D009374:Neoplasms, Experimental / Q000378:metabolism* / Q000473:pathology; D010569:Perylene / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D019800:Phenol; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000493:pharmacokinetics*; D011809:Quinones / Q000493:pharmacokinetics*; D014407:Tumor Cells, Cultured
D017319:Photosensitizing Agents; D011809:Quinones; D019800:Phenol; D010569:Perylene; C048388:hypocrellin A