Department of Obstetrics and Gynecology, The Third Affiliated Hospital, Southern Medical University, Guangzhou, Guangdong 510630, China.
Department of Obstetrics and Gynecology, Affiliated Shenzhen Maternity & Child Healthcare Hospital, Southern Medical University, Shenzhen, Guangdong 518028, China.
ACS Appl Mater Interfaces. 2023 Mar 29;15(12):15893-15906. doi: 10.1021/acsami.3c00990. Epub 2023 Mar 20.
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.
肿瘤微环境中的低通透性和缺氧是限制多种治疗方法的重要因素。在此，构建了活性氧（ROS）触发的自组装纳米颗粒（RP-NPs）。将天然小分子大黄酸（Rh）包封在 RP-NPs 中作为声敏剂，高度聚集在肿瘤部位。然后，高组织通透性超声（US）辐射通过 Rh 的激发和声空化诱导肿瘤细胞凋亡，这促使缺氧肿瘤微环境中迅速产生大量 ROS。此外，通过 ROS 触发和破坏新设计的前药 LA-GEM 中的硫缩酮键结构，实现了吉西他滨（GEM）的快速靶向释放。声动力学疗法（SDT）通过线粒体途径增加实体瘤的组织通透性并主动破坏氧化还原稳态，以杀死缺氧肿瘤细胞，触发对 GEM 的反应机制协同增强了化疗效果。化疗-声动力学联合治疗方法高效且无创，有望应用于消除缺氧肿瘤，例如希望保持生殖功能的宫颈癌（CCa）患者。
