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- W188499503 abstract "Photochemical internalisation (PCI) is a technique which enhances targeted drugdelivery using light in combination with a photosensitiser. It is a modification ofphotodynamic therapy (PDT) which involves sub-lethal photodynamic treatment tomodify the intracellular distribution of co-administered drugs and other agents whichare sequestered in lyso/endosomes. In this study, PDT and PCI using a sulfonatedchlorin, AmphinexTM (TPCS2a), in combination with two anti-cancer drugs, saporin orbleomycin, have been investigated both in vitro and in vivo.In vitro experiments initially examined the cell uptake, photostability and cellularlocalisation of Amphinex using A431 human epidermoid carcinoma cells and HN5human head and neck squamous cells. The cell killing effect after PDT and PCI in thepresence of saporin and bleomycin were assessed. The bioavailability and therapeuticefficacy were also compared with another two PCI photosensitisers, TPPS2a andAlPcS2a. The results indicate that PCI is able to induce the relocalisation of bleomycinand saporin inside cells and thereby enhance cell death.A new porphyrin-peptide bioconjugate of a cell penetrating peptide (CPP) andtetraphenylporphine was investigated for PDT and PCI. It was found that CPP peptideconjugation renders efficient cellular delivery of the tetraphenylporphine for use as aPDT and PCI sensitiser.The pharmacokinetics of Amphinex in normal and tumour-bearing rats was studiedusing quantitative fluorescence microscopy and chemical extraction. In vivo AmphinexPCI effects and the comparison with PDT were investigated in normal rat liver, colonand a syngeneic rat fibrosarcoma tumour models. Amphinex PCI showed a significantenhancement in inducing damage to normal tissues and tumour. The involvement ofapoptosis was also established using the TUNEL assay.This thesis has demonstrated that Amphinex has favourable properties for PDT and PCI.The consistent results from both in vitro and in vivo experiments indicate thatAmphinex has the potential for further clinical utilization." @default.
- W188499503 created "2016-06-24" @default.
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- W188499503 date "2010-03-28" @default.
- W188499503 modified "2023-09-26" @default.
- W188499503 title "Studies of photochemical internalisation: mechanisms and strategies in cancer therapeutics" @default.
- W188499503 hasPublicationYear "2010" @default.
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