Enhancing the photodynamic effect of hypericin in tumour spheroids by fractionated light delivery in combination with hyperoxygenation

Huygens, Ann; Kamuhabwa, Appolinary; Laethem, An Van; Roskams, Tania; Cleynenbreugel, Ben Van; Poppel, Hendrik Van; Agostinis, Patrizia; Witte, Peter de

doi:10.3892/ijo.26.6.1691

Cited by 16 publications

(16 citation statements)

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“…However, in a previous study of our group [119] we could show in an in vitro model that fractionated PDT (with light/dark intervals of 45/60 s) with both, Hyp and AlPcS 4 as sensitizers, decreases PDT-induced formation of ROS and overall cytotoxicity; this effect could be reversed by addition of BCNU (1,3-bis-(2-chlorethyl)-1-nitrosurea), an inhibitor of glutathione reductase, suggesting that dark intervals during irradiation allow this enzyme to regenerate GSH which was oxidized by PDT-produced reactive oxygen species [119]. These results are substantiated by a study of Huygens et al, showing that in tumor spheroids fractionated irradiation with dark intervals ranging from 1 to 10 min did not enhance PDT efficiency unless sufficient oxygen supply was provided [184].…”

Section: Anti-angiogenic Mechanisms Of Hypsupporting

confidence: 63%

Cellular Mechanisms and Prospective Applications of Hypericin in Photodynamic Therapy

Kiesslich¹,

Krammer²,

Plaetzer

2006

CMC

111

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During the last decades, Photodynamic Therapy (PDT) has been established as a powerful alternative approved by health agencies of several countries for treatment of various malignant and some non-malignant diseases. PDT makes use of the light-induced destruction of target cells by formation of cytotoxic products in the presence of a photosensitizing agent and oxygen. The light-dependent tumor destructive properties of Hypericin have drawn attention to its promising application as a photosensitizer in the frame of PDT. Hypericin is a naturally occurring secondary metabolite in plants of the Hypericum genus, with Hypericum perforatum (St. John's wort) as it is a commonly known representative. This review focuses on the cellular mechanisms of Hypericin-based phototoxicity and provides an outlook for future application of Hypericin as a fluorescing and photosensitizing agent for diagnosis and treatment of cancerous diseases, respectively.

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Section: Anti-angiogenic Mechanisms Of Hypsupporting

confidence: 63%

Cellular Mechanisms and Prospective Applications of Hypericin in Photodynamic Therapy

Kiesslich¹,

Krammer²,

Plaetzer

2006

CMC

111

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“…One technique used normobaric oxygen that was simply bubbled through the solution that surrounded the spheroids, whereas the other approach used a biocompatible perfluorocarbon as oxygen carrier to hyperoxygenate the biological surrounding. 23,24 Because both modalities are rather easy to apply to the bladder cavity, PDT with PVP-hypericin combined with either of the techniques looks very promising for an efficient and selective whole-bladderwall photodynamic antitumoral treatment in a urological clinical setting. Obviously, further in vivo experiments are required to fully evaluate the potential of PVP-hypericin as a phototherapeutic, focusing on the combination of the compound with methods that enhance the oxygenation of the urothelium.…”

Section: Discussionmentioning

confidence: 99%

Biodistribution and photodynamic effects of polyvinylpyrrolidone-hypericin using multicellular spheroids composed of normal human urothelial and T24 transitional cell carcinoma cells

et al. 2011

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Polyvinylpyrrolidone (PVP)-hypericin is a potent photosensitizer that is used in the urological clinic to photodiagnose with high-sensitivity nonmuscle invasive bladder cancer (NMIBC). We examined the differential accumulation and therapeutic effects of PVP-hypericin using spheroids composed of a human urothelial cell carcinoma cell line (T24) and normal human urothelial (NHU) cells. The in vitro biodistribution was assessed using fluorescence image analysis of 5-μm cryostat sections of spheroids that were incubated with PVP-hypericin. The results show that PVP-hypericin accumulated to a much higher extent in T24 spheroids as compared to NHU spheroids, thereby reproducing the clinical situation. Subsequently, spheroids were exposed to different PDT regimes with a light dose ranging from 0.3 to 18J/cm 2 . When using low fluence rates, only minor differences in cell survival were seen between normal and malignant spheroids. High light fluence rates induced a substantial difference in cell survival between the two spheroid types, killing ∼80% of the cells present in the T24 spheroids. It was concluded that further in vivo experiments are required to fully evaluate the potential of PVP-hypericin as a phototherapeutic for NMIBC, focusing on the combination of the compound with methods that enhance the oxygenation of the urothelium. C 2011 Society of Photo-Optical Instrumentation Engineers (SPIE).

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“…Primary manipulation of the target tissue with electroporation, hyperoxygenation, treatment with PDT sensitizers and/or hyperthermia have been shown to increase the effectiveness of PDT [57][58][59][60]. Also, work is being done to increase the depth of penetration for PDT by designing photosensitizers that can be directly activated by infrared or nearinfrared light, wavelengths that can penetrate very deeply into tissue, or by creating constructs that include upconverting nanophosphors that can absorb light in these wavelengths and emit the activating visible light [61][62][63][64][65].…”

Section: Five-year Viewmentioning

confidence: 99%

Photodynamic therapy for malignant pleural mesothelioma: the future of treatment?

Friedberg

2011

Expert Review of Respiratory Medicine

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Malignant pleural mesothelioma is a deadly incurable cancer, with a median survival of approximately 9 months. The best available chemotherapy, arguably the standard of care, only yields a 40% response rate and an 11-week extension in median survival. Surgery, the modality most likely to be associated with prolonged remission, remains investigational and must always be combined with other modalities in an effort to treat the microscopic disease that will remain even after the most aggressive operations. One such modality, photodynamic therapy, is a light-based cancer treatment that has features making it particularly well suited as a component of a surgery-based multimodal treatment plan. Utilizing intraoperative photodynamic therapy has enabled development of a less drastic surgical procedure that is also yielding some encouraging survival results. A unique aspect of photodynamic therapy is its stimulation of a tumor-directed immune response, a feature that offers promise for designing future treatments.

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Enhancing the photodynamic effect of hypericin in tumour spheroids by fractionated light delivery in combination with hyperoxygenation

Cited by 16 publications

References 0 publications

Cellular Mechanisms and Prospective Applications of Hypericin in Photodynamic Therapy

Cellular Mechanisms and Prospective Applications of Hypericin in Photodynamic Therapy

Biodistribution and photodynamic effects of polyvinylpyrrolidone-hypericin using multicellular spheroids composed of normal human urothelial and T24 transitional cell carcinoma cells

Photodynamic therapy for malignant pleural mesothelioma: the future of treatment?

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