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Could clinical photochemical internalisation be optimised to avoid neuronal toxicity?

13 June 2017

International Journal of Pharmaceutics

The study aims to understand the effects of Photochemical Internalisation (PCI) treatment on mammalian peripheral nerve cells in order to minimise nerve toxicity in future clinical applications. PCI is a novel drug delivery technology founded upon Photodynamic Therapy (PDT). In PCI, low dose PDT can selectively rupture endo/lysosomal membranes by light activation of membrane-incorporated photosensitisers, facilitating intracellular drug release.

PCI has been tested in a phase 1, dose-escalation, first-in-man trial at UCLH with advanced head and neck cancer (HNC) and shown to be safe and tolerable. For PCI to be developed further, it is essential to understand whether nerve damage is an impending side effect when treating cancers within or adjacent to nervous system tissue.

Results from this study identified treatment parameters that could kill tumour cells but allow neurons and other cells of the nervous system to survive, suggesting cancers within or adjacent to nervous system tissue could be treated with this novel technology.

Future investigations will employ similar methodology to investigate whether neurons are still functioning following treatment and identify which biochemical pathways are responsible for this nerve sparing effect.

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