One-pot synthesis of a self-reinforcing cascade bioreactor for combined photodynamic/chemodynamic/starvation therapy
One-pot synthesis of a self-reinforcing cascade bioreactor for combined photodynamic/chemodynamic/starvation therapy
复制标题
用于光动力/化学动力/饥饿联合治疗的自强化级联生物反应器的一锅合成
DOI：
10.1016/j.jcis.2021.03.173
复制
发表时间：
2021
影响因子：
9.9
通讯作者：
Wong Chun-Yuen
中科院分区：
文献类型：
--
作者：
Zhang Li;Yang Zhe;He Wenshan;Ren Jinghua;Wong Chun-Yuen
光动力疗法(PDT)和化学动力学疗法(CDT)的结合已经引起了人们的极大兴趣，但肿瘤的缺氧和谷胱甘肽(GSH)的过量生产仍然限制了它们的进一步应用。本论文采用一锅法构建了一种具有产氧和清除GSH/葡萄糖能力的智能活性氧(ROS)纳米发电机Ce6/Gox@ZIF-8/PDA@MnO2(简称CGZPM；Ce6、Gox、ZIF-8、PDA、MnO2分别为氯素e6、葡萄糖氧化酶、分子筛咪唑骨架-8、多多巴胺和二氧化锰)。肿瘤细胞摄取外源MnO2后，在酸性pH条件下迅速降解，过表达过氧化氢和谷胱甘肽，产生丰富的Mn2+和O2，最终实现多功能。Mn2+是理想的Fenton样试剂和磁共振(MR)造影剂，而O2通过缺氧缓解促进PDT，并促进Gox氧化葡萄糖进行饥饿治疗(ST)。得益于基于Gox的糖酵解过程，通过Mn2+介导的类Fenton反应，产生了足够的过氧化氢来提高CDT的效率。值得注意的是，MnO2和PDA可以通过消耗GSH来降低肿瘤的抗氧化活性，导致PDT/CDT显著增加。这种具有调节肿瘤微环境(TME)能力的新型级联生物反应器为基于ROS的联合治疗模式开辟了新的机会。
The combination of photodynamic therapy (PDT) and chemodynamic therapy (CDT) have attracted a great deal of interest, but tumor hypoxia and glutathione (GSH) overproduction still limit their further applications. Herein, an intelligent reactive oxygen species (ROS) nanogenerator Ce6/GOx@ZIF-8/PDA@MnO2(denoted as CGZPM; Ce6, GOx, ZIF-8, PDA, MnO2are chlorin e6, glucose oxidase, zeolitic imidazolate framework-8, polydopamine and manganese dioxide respectively) with O2-generating and GSH-/glucose-depleting abilities was constructed by a facile and green one-pot method. After intake by tumor cells, the outer MnO2was rapidly degraded by the acidic pH, and the overexpression of hydrogen peroxide (H2O2) and GSH with abundant Mn2+and O2produced would eventually achieve multifunctionality. The Mn2+acted as an ideal Fenton-like agent and magnetic resonance (MR) imaging contrast agent, while the O2promoted the PDT via hypoxia relief and facilitated the intratumoral glucose oxidation by GOx for starvation therapy (ST). Benefiting from the GOx-based glycolysis process, sufficient H2O2was generated to improve the CDT efficacy through Mn2+-mediated Fenton-like reaction. Notably, MnO2and PDA could decrease the tumor antioxidant activity by consuming GSH, resulting in remarkably enhanced PDT/CDT. Such a novel cascade bioreactor with tumor microenvironment (TME)-modulating capability opens new opportunities for ROS-based and combinational treatment paradigms.