声动力疗法
活性氧
肿瘤缺氧
肿瘤微环境
癌症研究
材料科学
生物物理学
吉西他滨
细胞凋亡
化疗
细胞生物学
化学
生物化学
医学
生物
放射治疗
肿瘤细胞
内科学
作者
Yibing Li,Gang Li,Jiashan Xie,Lixue Wei,Shuping Xiong,Kunyi Yu,Bingchen Zhang,Shengtao Wang,Zibo Li,Yan Tang,Guimei Chen,Zhongjun Li,Zhiqiang Yu,Xuefeng Wang
标识
DOI:10.1021/acsami.3c00990
摘要
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.
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