Could clinical photochemical internalisation be optimised to avoid neuronal toxicity?

Could clinical photochemical internalisation be optimised to avoid neuronal toxicity?
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可以优化临床光化学内部化以避免神经元毒性吗?

DOI:
10.1016/j.ijpharm.2017.05.071
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发表时间:
2017-08-07
影响因子:
5.8
通讯作者:
Woodhams JH
Woodhams JH
中科院分区:
医学2区
文献类型:
--
作者:
O'Rourke C;Hopper C;MacRobert AJ;Phillips JB;Woodhams JH

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光化学内化(PCI)是一种新型的药物传递技术,低剂量光动力疗法(PDT)可以通过膜结合光敏剂的光激活来选择性地破坏内切/溶酶体,促进肿瘤治疗中的细胞内药物释放。为了进一步发展经皮冠状动脉介入治疗,重要的是要了解在治疗神经系统组织内或邻近的癌症时,神经损伤是否是即将发生的副作用。背根神经节(DRG)神经元及其伴生的卫星胶质细胞在光敏剂四苯基卟啉(TPPS2a)或四苯氯二磺酸盐(TPCS2a)和博莱霉素共同孵育后,在3D共培养系统中进行PCI处理。3D共培养模型的结果表明,尽管轴突长度受到影响,但癌细胞系PCI30和卫星胶质细胞比神经元和混合胶质细胞对PCI更敏感。在足以杀死肿瘤细胞的条件下,培养的神经元在经皮冠状动脉介入治疗中存活下来,这表明神经系统组织内或邻近的癌症可以用这项新技术治疗。
Photochemical 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.
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