Could clinical photochemical internalisation be optimised to avoid neuronal toxicity?

摘要

class="kwd-title">Chemical compounds studied in this article: Tetraphenylchlorin disulfonate (PubChem CID: 44177671), Meso-tetraphenylporphine (PubChem CID: 70186), Bleomycin (PubChem CID: 5360373) class="kwd-title">Abbreviations: PCI, Photochemical Internalisation; PDT, Photodynamic therapy; ROS, Reactive oxygen species; HNC, Head and neck cancer; TPPS2a, Meso-tetraphenylporphine; TPCS2a, Tetraphenylchlorin disulfonate; 3D, Three-dimensional; DRG, Dorsal root ganglion; CNS, Central nervous system class="kwd-title">Keywords: Photochemical Internalisation, Nervous system, 3D culture models, Bleomycin, Photosensitisers class="head no_bottom_margin" id="abs0010title">AbstractPhotochemical Internalisation (PCI) is a novel drug delivery technology in which low dose photodynamic therapy (PDT) can selectively rupture endo/lysosomes by light activation of membrane-incorporated photosensitisers, facilitating intracellular drug release in the treatment of cancer. For PCI to be developed further, it is important to understand whether nerve damage is an impending side effect when treating cancers within or adjacent to nervous system tissue. Dorsal root ganglion (DRG) neurons and their associated satellite glia were subjected to PCI treatment in a 3D co-culture system following incubation with photosensitisers: meso-tetraphenylporphine (TPPS2a) or tetraphenylchlorin disulfonate (TPCS2a) and Bleomycin. Results from the use of 3D co-culture models demonstrate that a cancer cell line PCI30 and satellite glia were more sensitive to PCI than neurons and mixed glial cells, athough neurite length was affected. Neurons in culture survived PCI treatment under conditions sufficient to kill tumour cells, suggesting cancers within or adjacent to nervous system tissue could be treated with this novel technology.