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.

[1]  J. Tulip,et al.  Synthesis and biodistribution of 14C‐radiolabelled hypocrellin B , 1995 .

[2]  J. Lown,,et al.  Photosensitization with anticancer agents. 15. Perylenequinonoid pigments as potential photodynamic therapeutic agents: formation of semiquinone radicals and reactive oxygen species on illumination. , 1993, Journal of photochemistry and photobiology. B, Biology.

[3]  J. Lown,,et al.  Photosensitization with anticancer agents 14. Perylenequinonoid pigments as new potential photodynamic therapeutic agents: formation of tautomeric semiquinone radicals , 1992 .

[4]  J. Lown,,et al.  Photosensitization with anticancer agents 13. The production of singlet oxygen by halogenated and metal-ion-chelated perylenequinones , 1992 .

[5]  Zhenjun Diwu,et al.  Photosensitization by anticancer agents 12. Perylene quinonoid pigments, a novel type of singlet oxygen sensitizer , 1992 .

[6]  Z. Diwu,et al.  A Simple High-Yielding Approach to Perylenequinone from the Novel One- Step Double Coupling Reaction of 1,2-Naphthoquinone. , 1992 .

[7]  R. Santus,et al.  Protection against light-activated photofrin II killing of tumor cells by nitroimidazoles. , 1992, Radiation research.

[8]  E. Cao,et al.  DNA damage induced by hypocrellin-A photosensitization. , 1992, International journal of radiation biology.

[9]  A. Kaye,et al.  SUBCELLULAR LOCALIZATION OF PORPHYRINS USING CONFOCAL LASER SCANNING MICROSCOPY , 1991, Photochemistry and photobiology.

[10]  J Moan,et al.  Location of P-II and AlPCS4 in human tumor LOX in vitro and in vivo by means of computer-enhanced video fluorescence microscopy. , 1991, Cancer letters.

[11]  J. Lown,,et al.  HYPOCRELLINS and THEIR USE IN PHOTOSENSITIZATION * , 1990, Photochemistry and photobiology.

[12]  L. Zang,et al.  Characteristics of the primary reaction of hypocrellin A photosensitization. , 1989, Science in China. Series B, Chemistry, life sciences & earth sciences.

[13]  F. Nw,et al.  Photodynamic action of hypocrellin A on hepatoma cell mitochondria and microsomes , 1989 .

[14]  C. Longsheng,et al.  Effect of hypocrellin A sensitization on the lateral mobility of cell membrane proteins. , 1988 .

[15]  C. J. Koch,et al.  Fluorescence immunohistochemical detection of hypoxic cells in spheroids and tumours. , 1987, British Journal of Cancer.

[16]  R. Pagano,et al.  A vital stain for the Golgi apparatus. , 1985, Science.

[17]  D. Chaplin,et al.  Cell selection from a murine tumour using the fluorescent probe Hoechst 33342. , 1985, British Journal of Cancer.

[18]  M. Terasaki,et al.  Localization of endoplasmic reticulum in living and glutaraldehyde-fixed cells with fluorescent dyes , 1984, Cell.

[19]  J. D. Chapman,et al.  Characteristics of the metabolism-induced binding of misonidazole to hypoxic mammalian cells. , 1983, Cancer research.

[20]  J. Tulip,et al.  Hypocrellins as photosensitizers for photodynamic therapy: a screening evaluation and pharmacokinetic study , 1996, Cancer Chemotherapy and Pharmacology.

[21]  J. Lown,,et al.  A simple high-yielding approach to perylenequinone from the novel one-step double coupling reaction of 1,2-naphtoquinone , 1992 .

[22]  T. Dougherty,et al.  Of what value is a highly absorbing photosensitizer in PDT? , 1991, Journal of photochemistry and photobiology. B, Biology.

[23]  R. V. Buskirk,et al.  A double-label in situ cytotoxicity assay using the fluorescent probes neutral red and BCECF-AM , 1990 .

[24]  N. Fu,et al.  [Photodynamic action of hypocrellin A on hepatoma cell mitochondria and microsomes]. , 1989, Zhongguo yao li xue bao = Acta pharmacologica Sinica.

[25]  J. Swanson.  Fluorescent labeling of endocytic compartments. , 1989, Methods in cell biology.

[26]  J. Wampler,et al.  Quantitative fluorescence microscopy using photomultiplier tubes and imaging detectors. , 1989, Methods in cell biology.

[27]  R. Pagano.  A fluorescent derivative of ceramide: physical properties and use in studying the Golgi apparatus of animal cells. , 1989, Methods in cell biology.

[28]  L B Chen,et al.  Fluorescent labeling of mitochondria. , 1989, Methods in cell biology.

[29]  M. Terasaki,et al.  Fluorescent labeling of endoplasmic reticulum. , 1989, Methods in cell biology.

[30]  L. Chen.  Chapter 7 Fluorescent Labeling of Mitochondria , 1988 .

[31]  L. Cheng,et al.  Effect of hypocrellin A sensitization on the lateral mobility of cell membrane proteins. , 1988, Journal of photochemistry and photobiology. B, Biology.