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能否优化临床光化学内化以避免神经元毒性?

Could clinical photochemical internalisation be optimised to avoid neuronal toxicity?

作者信息

O'Rourke Caitriona, Hopper Colin, MacRobert Alexander J, Phillips James B, Woodhams Josephine H

机构信息

Division of Surgery & Interventional Science, University College London, London, UK; Department of Biomaterials & Tissue Engineering, UCL Eastman Dental Institute, University College London, London, UK.

Academic Unit of Oral and Maxillofacial Surgery, UCL Eastman Dental Institute, London, UK.

出版信息

Int J Pharm. 2017 Aug 7;528(1-2):133-143. doi: 10.1016/j.ijpharm.2017.05.071. Epub 2017 Jun 1.

DOI:10.1016/j.ijpharm.2017.05.071
PMID:28579544
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5571751/
Abstract

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 (TPPS) or tetraphenylchlorin disulfonate (TPCSa) 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.

摘要

光化学内化(PCI)是一种新型药物递送技术,在该技术中,低剂量光动力疗法(PDT)可通过对膜结合光敏剂进行光激活来选择性地破坏内体/溶酶体,从而在癌症治疗中促进细胞内药物释放。为了进一步开发PCI,了解在治疗神经系统组织内或其附近的癌症时神经损伤是否是即将出现的副作用很重要。在用光敏剂:中-四苯基卟啉(TPPS)或四苯基氯二磺酸盐(TPCSa)和博来霉素孵育后,在三维共培养系统中对背根神经节(DRG)神经元及其相关的卫星神经胶质细胞进行PCI处理。三维共培养模型的结果表明,尽管神经突长度受到影响,但癌细胞系PCI30和卫星神经胶质细胞对PCI比神经元和混合神经胶质细胞更敏感。在足以杀死肿瘤细胞的条件下,培养的神经元在PCI处理后存活,这表明这种新技术可用于治疗神经系统组织内或其附近的癌症。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2b1c/5571751/f17266d9d92b/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2b1c/5571751/f17266d9d92b/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2b1c/5571751/f17266d9d92b/gr5.jpg

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二维和三维卵巢癌细胞培养中光动力疗法与放线菌素化疗的协同作用。
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Photochemical Internalization for Intracellular Drug Delivery. From Basic Mechanisms to Clinical Research.用于细胞内药物递送的光化学内化:从基本机制到临床研究
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