Université d'Aix-Marseille CNRS - UMR 7273, case 551, Avenue Escadrille Normandie-Niemen, 13397 Marseille cedex 20, France.
Org Biomol Chem. 2014 Feb 7;12(5):719-23. doi: 10.1039/c3ob42076k. Epub 2013 Dec 12.
Development of anti-cancerous theranostic agents is a vivid field. This article describes a theranostic approach that relies on the triggering of cancer cell death by generation of alkyl radicals at the right place and at the right time using the presence of active proteases in the tumour environment. Alkoxyamines (R(1)R(2)NOR(3)) are labile molecules that homolyze into nitroxides (R(1)R(2)NO˙) and reactive alkyl radicals (R(3)˙). They are used as a source of active alkyl radicals for curing and nitroxides for monitoring by Overhauser-enhanced magnetic resonance imaging (OMRI). Herein, the requirements needed for applying alkoxyamines are described: (i) highly selective activation of the alkoxyamine by specific proteases; (ii) fast homolysis of the alkoxyamine C-ON bond at physiological temperature; (iii) activation of cell death processes through an increase of the local oxidative stress or potential re-activation of the immune system due to short-lived alkyl radicals; and (iv) imaging of the tumor and the drug release by sensing the nitroxide by OMRI.
抗癌治疗药物的研发是一个非常活跃的领域。本文描述了一种治疗方法，该方法依赖于在肿瘤微环境中存在的活性蛋白酶在适当的位置和时间触发癌细胞死亡，通过生成烷基自由基来实现。烷氧基胺（R(1)R(2)NOR(3)）是不稳定的分子，容易均裂成氮氧自由基（R(1)R(2)NO˙）和反应性烷基自由基（R(3)˙）。它们可用作治疗用活性烷基自由基的来源，也可用作通过过氧化物增强磁共振成像（OMRI）监测的氮氧自由基的来源。本文中描述了应用烷氧基胺所需的要求：（i）通过特定蛋白酶高度选择性地激活烷氧基胺；（ii）在生理温度下烷氧基胺 C-ON 键快速均裂；（iii）通过增加局部氧化应激或由于短寿命烷基自由基而重新激活免疫系统来激活细胞死亡过程；以及（iv）通过 OMRI 检测氮氧自由基来对肿瘤和药物释放进行成像。
