肿瘤环境中的低渗透性和低氧环境是限制多种治疗的重要因素。因此，本文构建了以自组装的反应性氧自由基(RP-NPs)为触发器的自组装纳米颗粒，将天然的小分子大黄素(Rh)封装到纳米颗粒中作为在肿瘤部位高度累积的声敏剂。然后，高渗透性和高穿透性的超声辐照通过Rh的激发和声学空化诱导肿瘤细胞凋亡，从而促进了缺氧的肿瘤微环境中大量ROS的快速产生。此外，具有创新设计的去硫代醚键结构的前药LA-GEM可以被ROS触发并断裂，从而实现快速靶向释放吉西他滨(GEM)。声动力疗法(SDT)通过线粒体通路增加固体肿瘤的组织渗透性并积极干扰氧化还原平衡，同时触发对GEM的反应机制，从而协同增强化疗效果。这种化学声动力联合治疗方法具有高效和无创的特点，可以有效消除缺氧肿瘤，特别是对于希望保持生育功能的宫颈癌（CCa）患者，具有很大的应用前景。

The hypopermeability and hypoxia in the tumor milieu are important factors that limit multiple treatments. Herein, the reactive oxygen species (ROS)-triggered self-assembled nanoparticles (RP-NPs) was constructed. The natural small molecule Rhein (Rh) was encapsulated into RP-NPs as a sonosensitizer highly accumulated at the tumor site. Then highly tissue-permeable ultrasound (US) irradiation induced apoptosis of tumor cells through the excitation of Rh and acoustic cavitation, which prompted the rapid production of large amounts of ROS in the hypoxic tumor microenvironment. In addition, the thioketal bond structures in the innovatively designed prodrug LA-GEM were triggered and broken by ROS to achieve rapid targeted release of the gemcitabine (GEM). Sonodynamic therapy (SDT) increased the tissue permeability of solid tumors and actively disrupted redox homeostasis via mitochondrial pathways to kill hypoxic tumor cells, and the triggered response mechanism to GEM synergistically amplified the effect of chemotherapy. The chemo-sonodynamic combinational treatment approach is highly effective and noninvasive, with promising applications for hypoxic tumor elimination, such as in cervical cancer (CCa) patients who want to maintain their reproductive function.