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Enhanced photodynamic destruction of a transplantable fibrosarcoma using photochemical internalisation of gelonin
- Source :
- British Journal of Cancer
- Publication Year :
- 2005
- Publisher :
- Springer Science and Business Media LLC, 2005.
-
Abstract
- Photochemical internalisation (PCI) is a technique for releasing biologically active macromolecules from endocytic vesicles by light activation of a photosensitiser localised in the same vesicles of targeted cells. This study investigated the PCI of the toxin gelonin as a way of enhancing the effect of photodynamic therapy (PDT) on a human malignant fibrous histiocytoma transplanted into nude mice using the photosensitiser disulphonated aluminium phthalocyanine (AlPcS(2a)). Pharmacokinetic studies after intraperitoneal administration showed that the serum level of AlPcS(2a) fitted a biexponential model (half-lives of 1.8 and 26.7 h). The tumour concentration was roughly constant up to 48 h, although fluorescence microscopy showed that the drug location was initially mainly vascular, but became intracellular by 48 h. To compare PDT with PCI, 48 h after intraperitoneal injection of 10 mg kg(-1) AlPcS(2a), and 6 h after direct intratumour injection of 50 microg gelonin (PCI) or a similar volume of phosphate-buffered saline (PDT controls), tumour-bearing animals were exposed to red light (150 J cm(-2)). Complete response was observed for more than 100 days in 50% of the PCI tumours but only 10% of the PDT tumours (P0.01). In tumours examined histologically 4 days after light delivery, the depth of necrosis was 3-4 mm after PDT, but 7 mm after PCI. The deeper effect after PCI demonstrates that the light fluence needed to kill tumour is less than with PDT. We conclude that PCI with gelonin can markedly enhance the effect of PDT on this type of tumour and may have a role clinically as an adjunct to surgery to control localised disease.
- Subjects :
- Cancer Research
Indoles
sarcoma
Necrosis
medicine.medical_treatment
Transplantation, Heterologous
Intraperitoneal injection
Mice, Nude
Photodynamic therapy
Biology
Photochemistry
Mice
AlPcS2a
In vivo
Organometallic Compounds
medicine
Animals
Humans
Infusions, Parenteral
gelonin
Gelonin
photochemical internalisation
Fibrosarcoma
Plant Proteins
Mice, Inbred BALB C
Photosensitizing Agents
Histiocytoma, Benign Fibrous
Cytoplasmic Vesicles
medicine.disease
Antineoplastic Agents, Phytogenic
Disease Models, Animal
Treatment Outcome
Endocytic vesicle
Photochemotherapy
photodynamic therapy
Oncology
Conventional PCI
Ribosome Inactivating Proteins, Type 1
medicine.symptom
Translational Therapeutics
pharmacokinetics
therapeutics
Half-Life
Subjects
Details
- ISSN :
- 15321827 and 00070920
- Volume :
- 92
- Database :
- OpenAIRE
- Journal :
- British Journal of Cancer
- Accession number :
- edsair.doi.dedup.....f41c5fcada47b8e2aaaf1253220f17b0