Abstract：
Nitric oxide (NO) and reactive oxygen species (ROS) embody excellent potential in cancer therapy. However, as a small molecule, their targeted delivery and precise, controllable release are urgently needed to achieve accurate cancer therapy. In this paper, a novel US-responsive bifunctional molecule (SD) and hyaluronic acid-modified MnO2 nanocarrier was developed, and a US-responsive NO and ROS controlled released nanoplatform was constructed. US can trigger SD to release ROS and NO simultaneously at the tumor site. Thus, SD served as acoustic sensitizer for sonodynamic therapy and NO donor for gas therapy. In the tumor microenvironment, the MnO2 nanocarrier can effectively deplete the highly expressed GSH, and the released Mn2+ can make H2O2 to produce .OH by Fenton-like reaction, which exhibited a strong chemodynamic effect. The high concentration of ROS and NO in cancer cell can induce cancer cell apoptosis ultimately. In addition, toxic ONOO-, which was generated by the reaction of NO and ROS, can effectively cause mitochondrial dysfunction, which induced the apoptosis of tumor cells. The 131I was labeled on the nanoplatform, which exhibited internal radiation therapy for tumor therapy. In -vitro and -vivo experiments showed that the nanoplatform has enhanced biocompatibility, and efficient anti-tumor potential, and it achieves synergistic sonodynamic/NO/chemodynamic/radionuclide therapy for cancer.
摘要：
一氧化氮（NO）和活性氧（ROS）在癌症治疗中具有出色的潜力。然而,作为一个小分子，他们有针对性的交付和精确，可控释放是实现准确的癌症治疗迫切需要。在本文中,开发了一种新型的US响应双功能分子（SD）和透明质酸修饰的MnO2纳米载体，并构建了US响应NO和ROS受控释放的纳米平台。US可以触发SD在肿瘤部位同时释放ROS和NO。因此，SD用作声动力疗法的声学敏化剂和气体疗法的NO供体。在肿瘤微环境中，MnO2纳米载体可以有效地耗尽高表达的GSH，释放的Mn2+可以使H2O2产生。OH通过类Fenton反应，表现出强烈的化学动力学效应。癌细胞中高浓度的ROS和NO可最终诱导癌细胞凋亡。此外,有毒的ONOO-，它是由NO和ROS反应产生的，能有效地引起线粒体功能障碍,诱导肿瘤细胞凋亡。131I在纳米平台上贴上标签，展示了用于肿瘤治疗的内部放射治疗。体外和体内实验表明，纳米平台具有增强的生物相容性，和有效的抗肿瘤潜力，它实现了协同声动力/NO/化学动力/放射性核素治疗癌症。
