Improved pharmacokinetics, biodistribution and necrosis in vivo using a new near infra-red photosensitizer: tetrahydroporphyrin tetratosylat

Schastak, Stanislaw; Jean, B.; Handzel, Romy; Kostenich, Genady; Hermann, Ralf; Sack, Ulrich; Orenstein, Arie; Wang, Yusheng; Wiedemann, Peter

doi:10.1016/j.jphotobiol.2004.11.006

Cited by 42 publications

(52 citation statements)

References 22 publications

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“…Treatment with appropriate light doses generates ROS and directly leads to cell death without any possible development of a resistance mechanism [15], [16]. As most of the antidrugs, photosensitizers exhibit a higher uptake by cancer vs normal cells, thus allowing a very selective eradication of the malignant tumor while sparing the surrounding tissue [15], [17]. Altogether PDT is rapid, it has no long-term side effects, and most importantly stimulates the immune system, thus maximizing the tumoricidal effect [18]–[20].…”

Section: Introductionmentioning

confidence: 99%

Efficient Photodynamic Therapy on Human Retinoblastoma Cell Lines

et al. 2014

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Photodynamic therapy (PDT) has shown to be a promising technique to treat various forms of malignant neoplasia. The photodynamic eradication of the tumor cells is achieved by applying a photosensitizer either locally or systemically and following local activation through irradiation of the tumor mass with light of a specific wavelength after a certain time of incubation. Due to preferential accumulation of the photosensitizer in tumor cells, this procedure allows a selective inactivation of the malignant tumor while sparing the surrounding tissue to the greatest extent. These features and requirements make the PDT an attractive therapeutic option for the treatment of retinoblastoma, especially when surgical enucleation is a curative option. This extreme solution is still in use in case of tumours that are resistant to conventional chemotherapy or handled too late due to poor access to medical care in less advanced country. In this study we initially conducted in-vitro investigations of the new cationic water-soluble photo sensitizer tetrahydroporphyrin-tetratosylat (THPTS) regarding its photodynamic effect on human Rb-1 and Y79 retinoblastoma cells. We were able to show, that neither the incubation with THPTS without following illumination, nor the sole illumination showed a considerable effect on the proliferation of the retinoblastoma cells, whereas the incubation with THPTS combined with following illumination led to a maximal cytotoxic effect on the tumor cells. Moreover the phototoxicity was lower in normal primary cells from retinal pigmented epithelium demonstrating a higher phototoxic effect of THPTS in cancer cells than in this normal retinal cell type. The results at hand form an encouraging foundation for further in-vivo studies on the therapeutic potential of this promising photosensitizer for the eyeball and vision preserving as well as potentially curative therapy of retinoblastoma.

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Section: Introductionmentioning

confidence: 99%

Efficient Photodynamic Therapy on Human Retinoblastoma Cell Lines

et al. 2014

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“…[28] There is also clear interest in bacteriochlorins as PDT sensitizers, and it has been reported that some naturally occurring bacteriochlorins are effective photosensitizers both in vitro and in vivo. [29,30] An interesting representative of this third generation of photosensitizers is a palladium-bacteriopheophorbide known as Tookad, which has been approved for phase III clinical studies. Tookad is derived from bacteriochlorophyll and, like most of the naturally occurring bacteriochlorins, is sensitive to oxygen, which results in rapid oxidation to the chlorin species.…”

Section: Introductionmentioning

confidence: 99%

New Halogenated Water‐Soluble Chlorin and Bacteriochlorin as Photostable PDT Sensitizers: Synthesis, Spectroscopy, Photophysics, and in vitro Photosensitizing Efficacy

et al. 2010

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Chlorin and bacteriochlorin derivatives of 5,10,15,20-tetrakis(2-chloro-5-sulfophenyl)porphyrin have intense absorptions in the phototherapeutic window, high water solubility, high photostability, low fluorescence quantum yield, long triplet lifetimes, and high singlet oxygen quantum yields. Biological studies revealed their negligible dark cytotoxicity, yet significant photodynamic effect against A549 (human lung adenocarcinoma), MCF7 (human breast carcinoma) and SK-MEL-188 (human melanoma) cell lines upon red light irradiation (cutoff λ<600 nm) at low light doses. Time-dependent cellular accumulation of the chlorinated sulfonated chlorin reached a plateau at 2 h, as previously observed for the related porphyrin. However, the optimal incubation time for the bacteriochlorin derivative was significantly longer (12 h). The spectroscopic, photophysical, and biological properties of the compounds are discussed in relevance to their PDT activity, leading to the conclusion that the bacteriochlorin derivative is a promising candidate for future in vivo experiments.

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“…the degree of tumor necrosis was measured utilizing the vital stain Evan's blue (10). this dye reflects the mechanism of tumor destruction (11).…”

Section: Irradiationmentioning

confidence: 99%

“…this dye reflects the mechanism of tumor destruction (11). To determine the phototherapeutic effect of the phthalocyanine derivatives, the degree of tumor necrosis was assessed after pdt following this technique (10). vital stain was performed by i.p.…”

Section: Irradiationmentioning

confidence: 99%

Comparative photodynamic therapy study using two phthalocyanine derivatives

Yslas

Milla

Romanini³

et al. 2010

Experimental and Therapeutic Medicine

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Abstract. in the present study, a comparative photodynamic therapy (pdt) study was performed using the phthalocyanine derivatives, Znpc(Och 3 ) 4 and Znpc(cF 3 ) 4 , in a mouse tumor model, under identical experimental procedures. We studied the ablation of tumors induced by pdt. the end-point was to compare the photodynamic efficacy of ZnPc(OCH 3 ) 4 and Znpc(cF 3 ) 4 . Znpc(Och 3 ) 4 and Znpc(cF 3 ) 4 were administered intraperitoneally at a dose of 0.2 mg/kg body weight. the injections of drugs were carried out in Balb/c mice bearing subcutaneously inoculated lm2 mouse mammary adenocarcinoma. histological examination and serum biochemical parameters were used to evaluate hepatic and renal toxicity and function. phototherapeutic studies were achieved employing a light intensity of 210 J/cm 2 . after pdt, tumoral regression analyses were carried out, and the degree of tumor cell death was measured utilizing the vital stain Evan's blue. in this pilot study, we revealed that the cytotoxic effect of Znpc(Och 3 ) 4 after pdt led to a higher success rate compared to Znpc(cF 3 ) 4 -pdt when both were intraperitoneally injectioned. Both phthalocynanine derivatives were able to induce ablation in the tumors. in summary, these results demonstrate the feasibility of Znpc(Och 3 ) 4 -or Znpc(cF 3 ) 4 -pdt and its potential as a treatment for small tumors. Introductionphotodynamic therapy (pdt) is a well-known procedure in the field of clinical medicine for the treatment of cancer, although there has also been research into its application for non-malignant disorders, such as psoriasis or actinic keratosis and for cases of choroidal neovascularization.the treatment is currently under active investigation for palliative or curative applications. pdt is an evolving cancer treatment that depends on three known and variable components: photosensitizer (pS), light and oxygen (1). pdt relies on selective accumulation of a pS in tumor tissue, which on illumination with light of appropriate wavelengths, generates reactive oxygen species, particularly singlet oxygen, and destroys tumor tissue (2). in recent years, treatment of cancer by pdt has gained considerable interest due to its intrinsic dual selectivity. the pS localizes in the malignant tissue, and the light is spatially focused on the lesion (3). phthalocyanines (pcs) are pSs of the dye family. pcs and their derivatives have been intensively investigated as the second generation pSs for pdt (4). most of the activity of clinical pSs in the dye family comes from phthalocyanines and their relatives, the naphthalocyanines. these structures are active in a range of 650-850 nm. most dyes are hydrophobic requiring delivery agents, such as a liposomal preparation, for clinical use. Linking dyes to a variety of metals improves efficacy. aluminum, zinc and silicon appear to offer the best pdt activity (5).the development of new compounds as potential pSs in PDT is of great scientific interest. The advantage of this therapy over available therapies is the high selectivity of tumor des...

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Improved pharmacokinetics, biodistribution and necrosis in vivo using a new near infra-red photosensitizer: tetrahydroporphyrin tetratosylat

Cited by 42 publications

References 22 publications

Efficient Photodynamic Therapy on Human Retinoblastoma Cell Lines

Efficient Photodynamic Therapy on Human Retinoblastoma Cell Lines

New Halogenated Water‐Soluble Chlorin and Bacteriochlorin as Photostable PDT Sensitizers: Synthesis, Spectroscopy, Photophysics, and in vitro Photosensitizing Efficacy

Comparative photodynamic therapy study using two phthalocyanine derivatives

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