Permeation of Hypericin in Spheroids Composed of Different Grade Transitional Cell Carcinoma Cell Lines and Normal Human Urothelial Cells

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

doi:10.1097/01.ju.0000162037.49102.56

Cited by 27 publications

(30 citation statements)

References 15 publications

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“…[11][12][13] The mechanism underlying the tumoritropic characteristics of the selectivity is not fully understood. It is assumed that the enhanced uptake of hypericin is secondary to a loss of intercellular adhesion in malignant tissue (e.g., by a decreased expression of E-cadherin in cancer cells 14,15 ), resulting in an enhanced intralesional migration of the compound by a paracellular route.…”

Section: Introductionmentioning

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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Section: Introductionmentioning

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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“…Preparation and characterization of urothelial cultures was done as previously described (47,48). Briefly, TRPV4 +/+ and TRPV4 -/-mice were catheterized and sacrificed.…”

Section: Figurementioning

confidence: 99%

Deletion of the transient receptor potential cation channel TRPV4 impairs murine bladder voiding

Gevaert¹,

Vriens²,

Segal³

et al. 2007

J. Clin. Invest.

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Here we provide evidence for a critical role of the transient receptor potential cation channel, subfamily V, member 4 (TRPV4) in normal bladder function. Immunofluorescence demonstrated TRPV4 expression in mouse and rat urothelium and vascular endothelium, but not in other cell types of the bladder. Intracellular Ca 2+ measurements on urothelial cells isolated from mice revealed a TRPV4-dependent response to the selective TRPV4 agonist 4α-phorbol 12,13-didecanoate and to hypotonic cell swelling. Behavioral studies demonstrated that TRPV4 -/-mice manifest an incontinent phenotype but show normal exploratory activity and anxietyrelated behavior. Cystometric experiments revealed that TRPV4 -/-mice exhibit a lower frequency of voiding contractions as well as a higher frequency of nonvoiding contractions. Additionally, the amplitude of the spontaneous contractions in explanted bladder strips from TRPV4 -/-mice was significantly reduced. Finally, a decreased intravesical stretch-evoked ATP release was found in isolated whole bladders from TRPV4 -/-mice. These data demonstrate a previously unrecognized role for TRPV4 in voiding behavior, raising the possibility that TRPV4 plays a critical role in urothelium-mediated transduction of intravesical mechanical pressure.

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“…In addition to the fact that intracellular uptake of HY is higher in cancerous cells, subsequent studies unraveled other possible contributing factors to its selective accumulation at tissue level 30,68. For instance, Huygens et al 30.…”

Section: Photodynamic Properties Of Hypericinmentioning

confidence: 99%

“…For instance, Huygens et al 30. studied human bladder cell carcinoma using a 3-dimensional (3D) spheroid model, and reported that the loss in intercellular adhesion due to the reduced expression of a transmembrane adhesion protein, E-cadherin, plays a pivotal role in the selective uptake of HY.…”

Section: Photodynamic Properties Of Hypericinmentioning

confidence: 99%

New Frontier in Hypericin-Mediated Diagnosis of Cancer with Current Optical Technologies

2011

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Photosensitizers (PSs) have shown great potentials as molecular contrast agents in photodynamic diagnosis (PDD) of cancer. While the diagnostic values of PSs have been proven previously, little efforts have been put into developing optical imaging and diagnostic algorithms. In this article, we review the recent development of optical probes that have been used in conjunction with a potent PS, hypericin (HY). Various fluorescence techniques such as laser confocal microscopy, fluorescence urine cytology, endoscopy and endomicroscopy are covered. We will also discuss about image processing and classification approaches employed for accurate PDD. We anticipate that continual efforts in these developments could lead to an objective PDD and complete surgical clearance of tumors. Recent advancements in nanotechnology have also opened new horizons for PSs. The use of biocompatible gold nanoparticles as carrier for enhanced targeted delivery of HY has been attained. In addition, plasmonic properties of nanoparticles were harnessed to induce localized hyperthermia and to manage the release of PS molecules, enabling a better therapeutic outcome of a combined photodynamic and photothermal therapy. Finally, we discuss how nanoparticles can be used as contrast agents for other optical techniques such as optical coherence tomography and surface-enhanced Raman scattering imaging.

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Permeation of Hypericin in Spheroids Composed of Different Grade Transitional Cell Carcinoma Cell Lines and Normal Human Urothelial Cells

Cited by 27 publications

References 15 publications

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

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

Deletion of the transient receptor potential cation channel TRPV4 impairs murine bladder voiding

New Frontier in Hypericin-Mediated Diagnosis of Cancer with Current Optical Technologies

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