Liposome- or LDL-administered Zn (II)-phthalocyanine as a photodynamic agent for tumours. I. Pharmacokinetic properties and phototherapeutic efficiency

Reddi, Elena; Zhou, Chen; Biolo, Roberta; Menegaldo, E.; Jori, Giulio

doi:10.1038/bjc.1990.89

Cited by 144 publications

(80 citation statements)

References 24 publications

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“…Our ultrastructural studies with a PDT-treated experimental tumour further support the conclusion (Reddi et al, 1990) that Zn-Pc is a very efficient phototherapeutic agent. Extensive necrotic degeneration of the tumour tissues is obtained upon administration of 0.12 mg kg-' Zn-Pc, i.e.…”

Section: Discussionsupporting

confidence: 70%

“…As discussed in a previous paper (Reddi et al, 1990), Zn-Pc is selectively carried by serum lipoproteins, and hence it is likely that its release to malignant cells through receptor-mediated endocytosis of LDL plays an important role owing to the elevated number of LDL-receptors associated with neoplastic cells (Gal et al, 1981).…”

Section: Discussionmentioning

confidence: 99%

“…injection to Balb/c mice bearing a transplanted MS-2 fibrosarcoma in the right hind leg, and the irradiation of the tumour area with red light were the same as previously described (Reddi et al, 1990). …”

Section: Methodsmentioning

confidence: 99%

“…Previous studies from our laboratory (Reddi et al, 1990) indicate that liposome-delivered Zn(II)-phthalocyanine (ZnPc) is a promising candidate to replace HpD or its active components in the photodynamic therapy (PDT) of tumours. In the case of mice bearing an MS-2 fibrosarcoma that received 0.12 mg kg-' Zn-Pc, PDT treatment generates a tumour necrosis whose extent is at least as large as that obtained after injection of 5 mg kg-' HpD.…”

mentioning

confidence: 99%

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Zn(II)-phthalocyanine as a photodynamic agent for tumours. II. Studies on the mechanism of photosensitised tumour necrosis

Milanesi

Zhou²,

Biolo³

et al. 1990

Br J Cancer

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Summary The mechanism of tumour necrosis photosensitised by liposome-delivered Zn(II) phthalocyanine (Zn-Pc) has been studied in mice bearing a transplanted MS-2 fibrosarcoma. Ultrastructural analyses of tumour specimens obtained at different times after red light-irradiation (300 J cm-2, dose-rate 180 mW cm-2) indicate an early (3 h) photodamage of malignant cells especially at the level of the mitochondria and rough endoplasmic reticulum. The cellular damage becomes more evident between 6 h and 15 h after photodynamic therapy. On the other hand, the capillaries supplying the tumour tissue are modified at a much slower rate and appear to be severely damaged only after 15 h from irradiation, when the whole tissue becomes necrotic. Occasionally, mildly damaged capillaries are observed even at 72 h after irradiation. These findings support the hypothesis that low density lipoproteins (LDL) play a major role in the delivery of Zn-Pc to the tumour tissue; the photosensitiser is released specifically to malignant cells as a consequence of a receptor-mediated endocytosis of LDL.

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Section: Discussionsupporting

confidence: 70%

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

mentioning

confidence: 99%

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Zn(II)-phthalocyanine as a photodynamic agent for tumours. II. Studies on the mechanism of photosensitised tumour necrosis

Milanesi

Zhou²,

Biolo³

et al. 1990

Br J Cancer

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“…Among the non-substituted Pcs, zinc phthalocyanine (ZnPc) has been investigated as a possible second generation PDT sensitiser (Ginevra et al, 1990;Reddi et al, 1990). The material is highly insoluble in most common solvents and a proprietary liposomal formulation has been advanced for clinical trials (Schieweck et al, 1994).…”

mentioning

confidence: 99%

Hexadecafluorinated zinc phthalocyanine: photodynamic properties against the EMT-6 tumour in mice and pharmacokinetics using 65Zn as a radiotracer

Boyle

Rousseau²,

Kudrevich³

et al. 1996

Br J Cancer

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Summary Hexadecafluorinated zinc phthalocyanine (ZnPcF,6), an analogue of zinc phthalocyanine (ZnPc) in which all hydrogen atoms have been substituted by fluorine, was prepared as a single isomeric product via the condensation of tetrafluorophthalonitrile with zinc acetate. Fluorination renders the ZnPc soluble in most common solvents. The photodynamic properties and pharmacokinetics of the ZnPcF,6 were evaluated in EMT-6 tumour-bearing Balb/c mice using 65Zn-radiolabelled analogues. Both dyes, administered i.v. at fLmol kg-' as Cremophor emulsions, revealed good tumour uptake [approximately 8-9 per cent of the injected dose per g tissue (%ID g-')] at 24 h post injection (p.i.), with the fluorinated dye reaching higher concentrations (approximately 11%ID g -') at 48 h p.i. and subsequently higher tumour -blood ratios due to rapid blood clearance. ZnPcF,6 at a dose of 5 pmol kg-' (4.3 mg kg-') induced complete tumour regression after phototherapy (24 h p.i., 650 -700 nm band, 360 J cm-2, 200 mW cm -'). At a dose of 2 fimol kg-' and phototherapy at 24 h p.i., the tumour volume doubling time increased to 11 days vs 6 days for the control tumours. A similar tumour growth delay was observed when phototherapy was conducted at 48 h or 72 h after dye injection implying that tumour response correlates with tumour dye concentrations rather than serum concentrations. As a result of its low solubility, the administered dose of ZnPc was limited to 1 fimol kg-' and at this drug level significant tumour response was only observed when the dye was solubilised as the pyridinium salt. Isolation of the neoplastic cells after in vivo dye administration and in vitro exposure to red light followed by a colony formation assay showed that the ZnPcF,6 exhibited a 1-2 order of magnitude higher potential for direct cell killing as compared with Photofrin and about a five times lower efficiency than ZnPc. However, all three photosensitisers induced complete occlusion of tumour vasculature immediately after PDT, suggesting that tumour regression mainly resulted from vascular stasis. The ZnPcF,6 offers several advantages over ZnPc for clinical applications, including improved solubility in most solvents, resulting in facilitated drug formation, favourable pharmacokinetics as well as the potential use in fluorine magnetic resonance (F-MR) imaging.

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Photodynamic therapy of tumours with hexadecafluoro zinc phthalocyanine formulated in PEG-coated poly(lactic acid) nanoparticles

Allémann¹,

Rousseau²,

Brasseur³

et al. 1996

Int. J. Cancer

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Hexadecafluoro zinc phthalocyanine (ZnPcF16), a second-generation sensitizer for the photodynamic therapy (PDT) of cancer, was formulated in polyethylene-glycol-coated poly(lactic acid) nanoparticles (PEG-coated PLA-NP) and tested in EMT-6 tumour-bearing mice for its photodynamic activity. The tumour response was compared to that induced by the same dye formulated as a Cremophor EL (CRM) emulsion. Formulation in the biodegradable NP improved PDT response of the tumour while providing prolonged tumour sensitivity towards PDT.

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Liposome- or LDL-administered Zn (II)-phthalocyanine as a photodynamic agent for tumours. I. Pharmacokinetic properties and phototherapeutic efficiency

Cited by 144 publications

References 24 publications

Zn(II)-phthalocyanine as a photodynamic agent for tumours. II. Studies on the mechanism of photosensitised tumour necrosis

Zn(II)-phthalocyanine as a photodynamic agent for tumours. II. Studies on the mechanism of photosensitised tumour necrosis

Hexadecafluorinated zinc phthalocyanine: photodynamic properties against the EMT-6 tumour in mice and pharmacokinetics using 65Zn as a radiotracer

Photodynamic therapy of tumours with hexadecafluoro zinc phthalocyanine formulated in PEG-coated poly(lactic acid) nanoparticles

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