Zhang Li, Yang Zhe, He Wenshan, Ren Jinghua, Wong Chun-Yuen
Department of Chemistry, City University of Hong Kong, Tat Chee Avenue, Kowloon, Hong Kong Special Administrative Region.
Department of Breast and Thyroid Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.
J Colloid Interface Sci. 2021 Oct;599:543-555. doi: 10.1016/j.jcis.2021.03.173. Epub 2021 Apr 2.
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@MnO (denoted as CGZPM; Ce6, GOx, ZIF-8, PDA, MnO are chlorin e6, glucose oxidase, zeolitic imidazolate framework-8, polydopamine and manganese dioxide respectively) with O-generating and GSH-/glucose-depleting abilities was constructed by a facile and green one-pot method. After intake by tumor cells, the outer MnO was rapidly degraded by the acidic pH, and the overexpression of hydrogen peroxide (HO) and GSH with abundant Mn and O produced would eventually achieve multifunctionality. The Mn acted as an ideal Fenton-like agent and magnetic resonance (MR) imaging contrast agent, while the O promoted 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 HO was generated to improve the CDT efficacy through Mn-mediated Fenton-like reaction. Notably, MnO and 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.
光动力疗法（PDT）和化学动力疗法（CDT）的联合应用已引起广泛关注，但肿瘤缺氧和谷胱甘肽（GSH）的过量产生仍然限制了它们的进一步应用。在此，通过简便绿色的一锅法构建了一种具有产氧和消耗GSH/葡萄糖能力的智能活性氧（ROS）纳米发生器Ce6/GOx@ZIF-8/PDA@MnO（记为CGZPM；Ce6、GOx、ZIF-8、PDA、MnO分别为二氢卟吩e6、葡萄糖氧化酶、沸石咪唑酯骨架-8、聚多巴胺和二氧化锰）。肿瘤细胞摄取后，外部的MnO在酸性pH条件下迅速降解，产生的大量含锰和氧的过氧化氢（H₂O₂）和GSH的过表达最终将实现多功能性。锰作为理想的类芬顿试剂和磁共振（MR）成像造影剂，而氧通过缓解缺氧促进光动力疗法，并通过葡萄糖氧化酶促进肿瘤内葡萄糖氧化以进行饥饿疗法（ST）。受益于基于葡萄糖氧化酶的糖酵解过程，产生了足够的H₂O₂以通过锰介导的类芬顿反应提高化学动力疗法的疗效。值得注意的是，MnO和PDA可以通过消耗GSH降低肿瘤抗氧化活性，从而显著增强光动力疗法/化学动力疗法。这种具有肿瘤微环境（TME）调节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机遇。
