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一项比较5-氨基乙酰丙酸(5-ALA)和5-ALA甲酯诱导的内源性原卟啉IX与外源性原卟啉IX(PpIX)及PpIX二甲酯在人鼻咽癌异种移植瘤光动力诊断中的研究。

A study comparing endogenous protoporphyrin IX induced by 5-ALA and ALA-methyl ester with exogenous PpIX and PpIX dimethyl ester in photodynamic diagnosis of human nasopharyngeal carcinoma xenografts.

作者信息

Manivasager Vanaja, Yee Karen Kar Lye, Heng Paul Wan Sia, Soo Khee Chee, Olivo Malini

机构信息

Division of Medical Sciences, National Cancer Centre, Singapore 169610, Singapore.

出版信息

Int J Oncol. 2006 Oct;29(4):997-1002.

Abstract

5-Aminolevulinic acid (5-ALA) and its esters have been under intense investigation to enhance the endogenous production of protoporphyrin IX (PpIX) in tumour cells for the purpose of photodynamic diagnosis. In this study we have investigated the use of exogenous PpIX and its dimethyl ester (PME) and compared the results with endogenous PpIX produced via 5-ALA and ALA methyl ester (AME) in poorly differentiated NPC/CNE-2 nasopharyngeal carcinoma cells in both in vivo and in vitro systems. All prodrugs and photosensitizers were administered to tumour bearing balb/c nude mice either intravenously or topically. in vitro results show that 5-ALA induced more PpIX fluorescence when compared with AME in NPC/CNE-2 cells and PME showed better uptake than PpIX. in vivo results show that exogenous PpIX and PME show promise as good candidates as photosensitizers for photodynamic diagnosis as they exhibit significant selectivity between tumour tissue and normal tissue at 3 h. Modification of delivery vehicle used for application of exogenous PpIX and PME could allow for rapid uptake; better selectivity and localization of the photosensitizer.

摘要

5-氨基乙酰丙酸(5-ALA)及其酯类一直受到深入研究,目的是增强肿瘤细胞中原卟啉IX(PpIX)的内源性生成,用于光动力诊断。在本研究中,我们研究了外源性PpIX及其二甲酯(PME)的使用,并将结果与通过5-ALA和ALA甲酯(AME)在低分化NPC/CNE-2鼻咽癌细胞的体内和体外系统中产生的内源性PpIX进行了比较。所有前药和光敏剂均通过静脉注射或局部给药给予荷瘤balb/c裸鼠。体外结果表明,与NPC/CNE-2细胞中的AME相比,5-ALA诱导产生更多的PpIX荧光,且PME的摄取比PpIX更好。体内结果表明,外源性PpIX和PME作为光动力诊断的光敏剂显示出有望成为良好候选物,因为它们在3小时时在肿瘤组织和正常组织之间表现出显著的选择性。用于应用外源性PpIX和PME的递送载体的改性可以实现快速摄取;光敏剂具有更好的选择性和定位。

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