Department of Neurosurgery, the Affiliated Brain Hospital with Nanjing Medical University, Fourth Clinical College of Nanjing Medical University, 210029, China; Department of Neuro-Psychiatric Institute, the Affiliated Brain Hospital with Nanjing Medical University, Nanjing 210029, China.
Department of Neurosurgery, the Affiliated Brain Hospital with Nanjing Medical University, Fourth Clinical College of Nanjing Medical University, 210029, China.
J Control Release. 2020 Dec 10;328:100-111. doi: 10.1016/j.jconrel.2020.08.035. Epub 2020 Aug 26.
Single reactive oxygen species (ROS)-mediated therapy, photodynamic therapy (PDT) or chemodynamic therapy (CDT) is severely hindered in hypoxic solid tumor. Herein, to address the urgent challenge, a hypoxia-activated ROS burst liposome has been fabricated to achieve synergistic PDT/CDT that is initiated by the structural dissociation of poly(metronidazole) liposome in hypoxic tumor microenvironment (TME). The therapeutic enhancement of our ROS-blasting treatment is simultaneously regulated by external light-initiated PDT and endogenous iron oxide nanoclusters-triggered CDT, which is synergistically boosted and amplified by localized mild hyperthermia under 808/660 nm coirradiation. More importantly, in vitro and in vivo experiments demonstrate that electron-affinic poly(aminoimidazole) product from hypoxia-responsive transition of poly(metronidazole) polymers could efficiently enhance hypoxic cell apoptosis and induce solid tumor ablation. Thus, this work offers a potential hypoxia-activated ROS burst-PDT/CDT strategy with a superior antitumor efficacy, highlighting a promising clinical application.
单一活性氧物种 (ROS) 介导的治疗、光动力疗法 (PDT) 或化学动力学疗法 (CDT) 在缺氧实体瘤中受到严重阻碍。在此，为了解决这一紧迫挑战，设计了一种缺氧激活的 ROS 爆发脂质体，以实现协同 PDT/CDT，这是由聚（甲硝唑）脂质体在缺氧肿瘤微环境 (TME) 中的结构解离引发的。我们的 ROS 爆发治疗的治疗增强作用同时受到外部光引发的 PDT 和内源性氧化铁纳米簇触发的 CDT 的调节，在 808/660nm 共辐照下，局部温和热疗协同增强和放大了这两种作用。更重要的是，体外和体内实验表明，来自缺氧响应性聚（甲硝唑）聚合物转变的电子亲和性聚（氨基咪唑）产物可以有效地增强缺氧细胞凋亡并诱导实体瘤消融。因此，这项工作提供了一种具有优异抗肿瘤疗效的潜在缺氧激活的 ROS 爆发-PDT/CDT 策略，突出了其有希望的临床应用。
