State Key Laboratory of Rare Earth Resource Utilization, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, 130022, P. R. China.
School of Applied Chemistry and Engineering, University of Science and Technology of China, Hefei, 230026, P. R. China.
Small. 2022 Sep;18(38):e2204047. doi: 10.1002/smll.202204047. Epub 2022 Aug 23.
The efficiency of reactive oxygen species (ROS)-mediated cancer therapy is restrained by intrinsic characteristics in the tumor microenvironment (TME), such as overexpressed glutathione (GSH), hypoxia and limited efficiency of H O . In this work, intelligent copper-dropped calcium carbonate loading sonosensitizer Ce6 nanoparticles (Cu/CaCO @Ce6, CCC NPs) are established to realize TME-responsive self-supply of oxygen and successively Ca -overloading-strengthened chemodynamic therapy/sonodynamic therapy (CDT/SDT). CCC NPs release Ca , Cu , and Ce6 in weakly acid and GSH-excessive TME. Released Cu can not only consume GSH and turn into Cu via a redox reaction, but also provide CDT-creating hydroxyl radicals through the Fenton-like reaction. Under ultrasound irradiation, the intracellular oxidative stress is amplified profoundly relying on singlet oxygen outburst from SDT. Moreover, Ca influx aggravates the mitochondrial disruption, which further accelerates the oxidation level. The facile and feasible design of the Cu-dropped CaCO -based nanoregulators will be further developed as a paradigm in ROS-contributed cancer therapy.
活性氧（ROS）介导的癌症疗法的效率受到肿瘤微环境（TME）中固有特性的限制，例如过度表达的谷胱甘肽（GSH）、缺氧和 H 2 O 2 效率有限。在这项工作中，建立了智能的铜脱落碳酸钙负载声敏剂 Ce6 纳米粒子（Cu/CaCO 3 @Ce6，CCC NPs），以实现 TME 响应性自供氧，并相继进行钙过负荷增强的化学动力学治疗/声动力治疗（CDT/SDT）。CCC NPs 在弱酸性和 GSH 过表达的 TME 中释放 Ca、Cu 和 Ce6。释放的 Cu 不仅可以通过氧化还原反应消耗 GSH 并转化为 Cu，还可以通过芬顿样反应提供产生羟基自由基的 CDT。在超声辐射下，细胞内氧化应激通过 SDT 中来自单线态氧的爆发而被显著放大。此外，Ca 内流加剧了线粒体的破坏，这进一步加速了氧化水平。基于 Cu 脱落碳酸钙的纳米调节剂的这种简便可行的设计将进一步发展成为 ROS 参与的癌症治疗的范例。
