Chen Yu, Cao Haiqiong, Jiang Chaoqun, Li Youbin
School of Physics and Electronic Sciences, Hunan Provincial Key Laboratory of Flexible Electronic Materials Genome Engineering, Changsha University of Science and Technology, Changsha 410114, PR China.
School of Physics and Electronic Sciences, Hunan Provincial Key Laboratory of Flexible Electronic Materials Genome Engineering, Changsha University of Science and Technology, Changsha 410114, PR China.
J Colloid Interface Sci. 2025 Apr;683(Pt 2):930-943. doi: 10.1016/j.jcis.2024.12.228. Epub 2024 Dec 30.
Developing a catalytic nanoenzyme activated by the tumor microenvironment (TME) shows excellent potential for in situ cancer treatment. However, the rational design of a cascade procedure to achieve high therapeutic efficiency remains challenging. In this study, the colorectal TME-responsive multifunctional cascade nanoenzyme CuO@MnO@glucose oxidase (GOx)@hyaluronic acid (HA) was developed to target in situ cancer starvation/chemodynamic therapy (CDT)/photothermal therapy (PTT). First, the MnO nanolayer specifically decomposes within the acidic TME to generate Mn and oxygen (O), thereby alleviating the hypoxic TME. Subsequently, CuO can be vulcanized into CuS by overexpressing sulfuretted hydrogen (HS) gas in the colorectal tumor for a second near-infrared (NIR-II) light-triggered deep tissue PTT. CuS nanoparticles can react with hydrogen peroxide (HO) to generate hydroxyl radical (OH) for the CDT. In addition, GOx catalyzes the conversion of glucose into HO for starvation therapy and enhances the CDT efficiency by self-supplying HO. Interestingly, the generated reactive oxygen species (ROS) induce immunogenic cell death (ICD), which further activates adaptive cancer immunity for anti-tumor immunotherapy. Finally, therapeutic efficiency was greatly improved after coating with tumor-targeted HA. Collectively, these TME-responsive cascade nanoenzymes can realize PTT, CDT starvation therapy, and immunotherapy, paving the way for the design of TME-responsive cascade nanoenzymes for synergistically enhanced tumor-specific therapy.
开发一种由肿瘤微环境（TME）激活的催化纳米酶在原位癌症治疗中显示出巨大潜力。然而，设计一个能实现高治疗效率的级联程序仍然具有挑战性。在本研究中，开发了一种结直肠癌TME响应型多功能级联纳米酶CuO@MnO@葡萄糖氧化酶（GOx）@透明质酸（HA），用于靶向原位癌症饥饿/化学动力疗法（CDT）/光热疗法（PTT）。首先，MnO纳米层在酸性TME中特异性分解，生成锰和氧气（O），从而缓解缺氧的TME。随后，CuO可通过结直肠癌中过表达的硫化氢（HS）气体硫化成CuS，用于二次近红外（NIR-II）光触发的深部组织PTT。CuS纳米颗粒可与过氧化氢（HO）反应生成羟基自由基（OH）用于CDT。此外，GOx催化葡萄糖转化为HO用于饥饿疗法，并通过自身供应HO提高CDT效率。有趣的是，产生的活性氧（ROS）诱导免疫原性细胞死亡（ICD），这进一步激活适应性癌症免疫以进行抗肿瘤免疫治疗。最后，用肿瘤靶向性HA包被后，治疗效率大大提高。总的来说，这些TME响应型级联纳米酶可以实现PTT、CDT饥饿疗法和免疫疗法，为设计用于协同增强肿瘤特异性治疗的TME响应型级联纳米酶铺平了道路。
