一氧化氮供体在抗肿瘤应用中的研究进展

Research Progress of Nitric Oxide Donor in Antitumor Application

一氧化氮(nitric oxide,NO)是首个被发现参与细胞信号传导的内源性气体分子,广泛存在于人体内,参与多种生理过程。对NO作为气体信号分子的相关机制研究证实了NO在促血管舒张、抗感染、刺激软组织再生、防止血小板粘附等方面都发挥重要生理作用。在肿瘤细胞中,NO具有抗癌还是促癌作用由NO的浓度高低决定,其抗肿瘤活性具有较高的浓度依赖性。高浓度的NO能够与细胞内的超氧阴离子等反应,生成过氧亚硝酸根离子等活性氮物质,通过损伤癌细胞的DNA、抑制各种酶功能、破坏线粒体功能等途径诱导细胞凋亡。然而NO半衰期短且极易扩散,因此多使用NO供体提供NO气体分子以进行抗肿瘤治疗。NO供体可在金属离子、激光等外源性条件刺激下按需释放NO,将NO供体与其他纳米体系相结合形成NO递送系统,在特定部位释放NO,是发挥NO抗肿瘤疗效的有效策略。综述不同类型NO供体的作用机制,利用NO供体构建的NO递送系统用于抗肿瘤治疗的效果,并介绍NO介导的气体疗法联合化学动力学治疗、光动力治疗、放射治疗和化疗等在抗肿瘤治疗中的应用进展,以期为相关研究人员提供理论参考。

Nitric oxide(NO),the first discovered endogenous gas molecule participating in signal transduction pathway,widely exists in the human body and is involved in various physiological processes.The research on the relevant mechanisms of NO as a gas signaling molecule has confirmed its important physiological role in promoting vasodilation,preventing infection,stimulating soft tissue regeneration,and preventing platelet adhesion.In tumor cells,the cancer-inhibiting or cancer-promoting effect of NO is determined by its concentration,and the antitumor activity of NO has a high concentration dependence.High concentration of NO can react with intracellular superoxide anions and generate reactive nitrogen species such as peroxynitrite ions to induce apoptosis by damaging the DNA of cancer cells,inhibiting various enzyme functions,and disrupting mitochondrial functions.However,NO has a short half-life and is highly diffusible,so NO donors are widely used to provide NO gas molecule for antitumor treatments.NO donors can release NO on demand when stimulated by exogenous conditions such as metal ions and laser.Combining NO donors with other nanosystems to form NO delivery systems for the release of NO at specific sites is an effective strategy to exploit the anti-tumor effect of NO.This review summarizes the action mechanisms of different types of NO donors and the effects of NO delivery systems constructed using NO donors for anti-tumor therapy,and introduces the progress of NO-mediated gas therapy combined with chemodynamic therapy,photodynamic therapy,radiotherapy and chemotherapy for effective antitumor treatment,aiming to provide some theoretical reference for relevant researchers.