On the photodynamic therapy action spectrum of zinc phthalocyanine tetrasulphonic acid in vivo

Griffiths, John R.; Cruse-Sawyer, Janet E.; Wood, Stephen C.; Schofield, Jack; Brown, Stanley B.; Dixon, B.

doi:10.1016/1011-1344(94)07021-0

Cited by 44 publications

(34 citation statements)

References 11 publications

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“…LSBD, ZnTCPc 9.1 ±1.7 8.1 +3.6 11.9±2.2 13.3±3.6 11.9±3.6 ZnTSAPc 8.5 ± 1.7 8.7 ± 2.3 8.8 ± 2.1 8.8 ± 0.7 9.3 ± 2.3 ZnPPc 0.5 ± 1.2 3.5 ± 1.5 7.9 ± 3.1 6.5 ± 2.6 -ZnTSPc 10.7 ± 1.8 12.7 ± 2.8 13 ± 1.5 13.1 ± 2.0 wavelength shift of only 12 nm has a marked effect on the tumour response after PDT with ZnTSPc (Griffiths et al, 1994), and such a wavelength effect may account for the strong PDT response that we have observed with these substituted compounds.…”

Section: Sensitizermentioning

confidence: 96%

The photodynamic response of two rodent tumour models to four zinc (II)-substituted phthalocyanines

Cruse-Sawyer

Griffiths²,

Dixon³

et al. 1998

Br J Cancer

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Summary Four novel zinc (I1)-substituted phthalocyanines, varying in charge and hydrophobicity, were evaluated in vivo as new photosensitizers for photodynamic therapy. Two rat tumours with differing vascularity were used: a mammary carcinoma (LMC,) and a fibrosarcoma (LSBD1), with vascular components six times higher in the latter (10.8% ± 1.5) than in the former (1.8% ± 1.4). Each sensitizer was assessed for tumour response relative to normal tissue damage, and optimum doses were selected for further study, ranging from 0.5 to 20 mg kg-'. Interstitial illumination of the tumours was carried out using a 200-gm-core optical fibre with a 0.5 cm length of diffusing tip, at either 680 or 692 nm, depending on the sensitizer. Light doses of between 200 and 600 J were delivered at a rate of 100 mW from the 0.5-cm diffusing section of the fibre. Maximum mean growth delays ranged from 9 to 13.5 days depending on sensitizer and type of tumour, with the most potent photosensitizer appearing to be the cationic compound. Histopathological changes were investigated after treatment to determine the mechanism by which tumour necrosis was effected. The tumours had the appearance of an infarct and, under the conditions used, the observed damage was shown to be mainly due to ischaemic processes, although some direct tumour cell damage could not be ruled out.Keywords: photodynamic therapy; zinc phthalocyanines; rodent tumours; ischaemia Photodynamic therapy (PDT) is a method of cancer treatment that has been clinically applied to the eradication or palliation of tumours at various sites, including bladder (Benson, 1985), brain (Kaye et al, 1987), lung (Okunaka et al, 1991), chest wall (Sperduto et al, 1991), skin (Caimduff et al, 1994) and oesophagus (Moghissi et al, 1995). The only photosensitizer so far approved for general use is Photofrin, which is a complex mixture of porphyrin monomers and oligomers. However, this drug also has relatively low light absorption in the red region of the spectrum, where light penetration in tissue is greatest, and also induces a prolonged skin photosensitivity (Richter et al, 1991).To overcome the problems associated with the limited depth of light penetration, chemical purity and stability, low absorption coefficient and skin photosensitivity, possible alternatives to the haematoporphyrin photosensitizers have been investigated. One such group is the phthalocyanines, which are synthetic porphyrin analogues. A number of phthalocyanine compounds have been tested in vitro (Chan et al, 1991;Boyle et al, 1993) and in vivo (Barr et al, 1991;Boyle et al, 1992) and show sufficient potential for clinical use to merit further investigation. They demonstrate strong absorbance in the red region of the spectrum and the potential for a greater PDT effect is enhanced by the increased tissue penetration by light of longer wavelength. They also appear to induce a smaller degree of skin photosensitivity than haematoporhyrin derivative (HPD) under experimental conditions (Roberts et al, 1989) and the compounds st...

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Section: Sensitizermentioning

confidence: 96%

The photodynamic response of two rodent tumour models to four zinc (II)-substituted phthalocyanines

Cruse-Sawyer

Griffiths²,

Dixon³

et al. 1998

Br J Cancer

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“…According to these results, Zn-DIGP is approximately 20-times more phototoxic than the well-studied anionic phthalocyanine "Zn-PcS4" (7). (29,30) To determine the probable mechanism of Zn-DIGP's phototoxicity, the quantum yield of singlet oxygen was measured for compounds 1 -7 by monitoring the time-dependent photobleaching of …”

Section: Gpcs: Photophysical Properties and Phototoxicitymentioning

confidence: 99%

Photodynamic Agents with Anti-metastatic Activities

et al. 2013

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A new concept in multifunctional anticancer agents is demonstrated. Tetrakis-(diisopropylguanidino) zinc phthalocyanine (Zn-DIGP) exhibits excellent properties as a photodynamic therapy (PDT) agent, as well as potential anti-metastatic activities in vivo. Zn-DIGP exhibits good cellular uptake and low toxicity in the dark (EC50 > 80 M) and is well tolerated upon its intravenous injection into mice at 8 mg/kg. Upon photoexcitation with red laser light (660 nm), Zn-DIGP exhibits a high quantum yield for singlet oxygen formation (Φ 0.51) that results in potent phototoxicity to cell cultures (EC50 0.16 M). Zn-DIGP is also capable of inhibiting the formation of tumor colonies in the lungs of C57BL/6 mice injected with B16F10 cells. Zn-DIGP therefore inhibits cancer growth by both lightdependent and light-independent pathways. The anti-metastatic activities of Zn-DIGP possibly result from its ability to interfere with the signaling between chemokine CXCL10 and the G protein-coupled receptor CXCR3. Zn-DIGP is a competitive inhibitor of CXCR3 activation (IC50 = 3.8 M) and selectively inhibits downstream events such as CXCL10-activated cell migration. Consistent with the presence of feedback regulation between CXCR3 binding and CXCL10 expression, Zn-DIGP causes overexpression of CXCL10. Interestingly, Zn-DIGP binds to CXCR3 without activating the receptor yet is able to cause endocytosis and degradation of this GPCR. To the best of our knowledge, Zn-DIGP is the first PDT agent that can facilitate the photodynamic treatment of primary tumors while simultaneously inhibiting the formation of metastatic tumor colonies by a light-independent mode of action. ABSTRACTA new concept in multifunctional anti-cancer agents is demonstrated. Tetrakis-(diisopropylguanidino) zinc phthalocyanine "Zn-DIGP" exhibits excellent properties as a photodynamic therapy (PDT) agent, as well as potential anti-metastatic activities in vivo. Zn-DIGP exhibits good cellular uptake and low toxicity in the dark (EC 50 > 80 µM), and is well tolerated upon its intravenous injection into mice at 8 mg / kg. Upon photoexcitation with red laser light (660 nm), Zn-DIGP exhibits a high quantum yield for singlet oxygen formation (Φ ≈ 0.51) that results in potent phototoxicity to cell cultures (EC 50 ≈ 0.16 µM). Zn-DIGP is also capable of inhibiting the formation of tumor colonies in the lungs of C57BL/6 mice injected with B16F10 cells. Zn-DIGP therefore inhibits cancer growth by both light-dependent and light-independent pathways. The anti-metastatic activities of Zn-DIGP possibly result from its ability to interfere with the signaling between chemokine CXCL10 and the G protein-coupled receptor CXCR3. Zn-DIGP is a competitive inhibitor of CXCR3 activation (IC 50 = 3.8 µM), and it selectively inhibits downstream events such as CXCL10-activated cell migration. Consistent with the presence of feedback regulation between CXCR3 binding and CXCL10 expression, Zn-DIGP causes overexpression of CXCL10. Interestingly, Zn-DIGP binds to CXCR3 without activating the...

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“…For specific substituents pattern this can result in improved photodynamic activities compared to commercial photosensitizers (Ochsner 1996, Ball et al 1998). A few current examples are shown below and include unsymmetrically substituted derivatives 57 (Kudrevich et al 1997), the cationic derivative 58 (Fernández et al 1997), the neutral derivative 59 (Ball et al 1998) and the classic anionic derivative 60 (Griffiths et al 1994(Griffiths et al , 1997. "(Tetrabenzoporphyrinato)zinc(II)", an intermediate structure between that of porphyrins and phthalocyanines, has also been investigated in this respect.…”

Section: Photodynamic Therapy and Singlet Oxygen Productionmentioning

confidence: 99%