ALA and ALA hexyl ester in free and liposomal formulations for the photosensitisation of tumour organ cultures
ALA and ALA hexyl ester in free and liposomal formulations for the photosensitisation of tumour organ cultures
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DOI：
10.1038/sj.bjc.6600144
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发表时间：
2002-03-04
影响因子：
8.8
通讯作者：
Batlle, AMD
中科院分区：
文献类型：
--
作者：
Casas, A;Perotti, C;Batlle, AMD
尽管用5-氨基乙酰丙酸介导的光动力疗法成功地治疗了广泛的肿瘤，但5-氨基乙酰丙酸具有低脂溶性的事实限制了其临床应用。更亲脂的5-氨基乙酰丙酸前药和使用脂质体载体是旨在改善5-氨基乙酰丙酸跨膜进入的两种方法。在这项研究中，我们使用了5-氨基乙酰丙酸及其己酯在其自由和封装的配方，以比较其相应的内源性卟啉合成。使用鼠肿瘤培养物。我们发现，使用己酯和将5-氨基乙酰丙酸或己酯包埋到脂质体中都不会增加肿瘤卟啉合成的速率。通过光学和电子显微镜，它被证明是暴露的肿瘤外植体的游离或脂质体5-氨基乙酰丙酸和随后的照明诱导相同类型的亚细胞损伤。线粒体、内质网和质膜是光动力处理早期损伤最多的结构。在后期，观察到细胞质和细胞核解体。通过电子显微镜显示了内吞途径参与脂质体5-氨基乙酰丙酸掺入细胞，（C）2002 Cancer Research UK。
in spite of the wide range of tumours successfully treated with 5-aminolevulinic acid mediated photodynamic therapy, the fact that 5-aminolevulinic acid has low lipid solubility, limits its clinical application. More lipophilic 5-aminolevulinic acid prodrugs and the use of liposomal carriers are two approaches aimed at improving 5-aminolevulinic acid transmembrane access. In this study we used both 5-aminolevulinic acid and its hexyl ester in their free and encapsulated formulations to compare their corresponding endogenous synthesis of porphyrins. Employing murine tumour cultures. we found that, neither the use of hexyl ester nor the entrappment of either 5-aminolevulinic acid or hexyl ester into liposomes increase the rate of tumour porphyrin synthesis. By light and electronic microscopy it was demonstrated that exposure of tumour explants to either free or liposomal 5-aminolevulinic acid and subsequent illumination induces the same type of subcellullar damage. Mitochondria, endoplasmic reticulum and plasma membrane are the structures mostly injured in the early steps of photodynamic treatment. In a later stage, cytoplasmic and nuclear disintegration are observed. By electronic microscopy the involvement of the endocytic pathway in the incorporation of liposomal 5-aminolevulinic acid into the cells was shown, (C) 2002 Cancer Research UK.