Photochemical disruption of endocytic vesicles before delivery of drugs: a new strategy for cancer therapy.
Photochemical disruption of endocytic vesicles before delivery of drugs: a new strategy for cancer therapy.
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DOI：
10.1038/sj.bjc.6600138
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发表时间：
2002-02-12
影响因子：
8.8
通讯作者：
Berg, K
中科院分区：
文献类型：
--
作者：
Prasmickaite, L;Hogset, A;Selbo, P K;Engesaeter, B O;Hellum, M;Berg, K
开发用于药物特异性递送的方法是许多癌症治疗方法的重要问题。大多数大分子药物通过内吞作用进入细胞，并且由于不能从内吞囊泡中逃逸，最终在那里降解，这阻碍了它们的治疗用途。我们已经开发了一种称为光化学内化的方法，该方法基于光诱导的光化学反应，专门在照明部位（例如肿瘤）内破坏内吞囊泡。在这里，我们提出了一个新的药物输送概念的基础上光化学内化的原则-光化学破坏的内吞囊泡之前交付的大分子，导致即时的内体释放，而不是有害的留在内吞囊泡中的分子。以前，我们已经表明，在用大分子处理后施加的照明大大改善了它们在体外和体内的生物学效应。在这里，我们证明，暴露于光之前交付的蛋白毒素白树素改善白树素的效果在体外远远超过光后。然而，在体外转染与报告基因提供的非病毒和腺病毒载体增加超过10倍和6倍，分别通过光化学内化策略。可能涉及的细胞机制，和这种新方法的光化学内化概念在癌症治疗中的实际应用的潜力进行了讨论。英国癌症杂志（2002）86，652-657。DOI：10.1038/sj/bjc/6600138 www.bjcancer.com © 2002英国癌症研究中心
The development of methods for specific delivery of drugs is an important issue for many cancer therapy approaches. Most of macromolecular drugs are taken into the cell through endocytosis and, being unable to escape from endocytic vesicles, eventually are degraded there, which hinders their therapeutic usefulness. We have developed a method, called photochemical internalization, based on light-induced photochemical reactions, disrupting endocytic vesicles specifically within illuminated sites e.g. tumours. Here we present a new drug delivery concept based on photochemical internalization-principle – photochemical disruption of endocytic vesicles before delivery of macromolecules, leading to an instant endosomal release instead of detrimental stay of the molecules in endocytic vesicles. Previously we have shown that illumination applied after the treatment with macromolecules substantially improved their biological effect both in vitro and in vivo. Here we demonstrate that exposure to light before delivery of protein toxin gelonin improves gelonin effect in vitro much more than light after. However, in vitro transfection with reporter genes delivered by non-viral and adenoviral vectors is increased more than 10- and six-fold, respectively, by both photochemical internalization strategies. The possible cellular mechanisms involved, and the potential of this new method for practical application of photochemical internalization concept in cancer therapy are discussed. British Journal of Cancer (2002) 86, 652–657. DOI: 10.1038/sj/bjc/6600138 www.bjcancer.com © 2002 Cancer Research UK