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首页> 外文期刊>Advanced Functional Materials >Ultrasound-Activated Oxygen and ROS Generation Nanosystem Systematically Modulates Tumor Microenvironment and Sensitizes Sonodynamic Therapy for Hypoxic Solid Tumors
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Ultrasound-Activated Oxygen and ROS Generation Nanosystem Systematically Modulates Tumor Microenvironment and Sensitizes Sonodynamic Therapy for Hypoxic Solid Tumors

机译：超声激活的氧气和ROS生成纳米系统可系统调节肿瘤的微环境并敏化缺氧性固体肿瘤的声动力疗法。

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摘要

Sonodynamic therapy (SDT) is noninvasive and possesses high body-penetration depth, showing great potential for the treatment of deep-seated solid tumors. The efficacy of SDT, however, is limited by widespread hypoxia in solid tumors. Given this, an ultrasound-activated nanosystem is developed by integrating ferrate(VI) and protoporphyrin IX into biodegradable hollow mesoporous organosilica nanoplatforms, followed by assembling a phase-change material of lauric acid. The ferrate(VI) effectively reacts with water as well as overexpressed hydrogen peroxide and glutathione (GSH) in tumor cells, leading to tumor-microenvironment-independent oxygen production and in situ GSH depletion in tumors. More importantly, significant reactive oxygen species (ROS) overproduction is simultaneously achieved by protoporphyrin-augmented SDT and intracellular Fenton chemistry. Furthermore, the mild hyperthermia induced by ultrasound can trigger the phase change of lauric acid, achieving ultrasound-responsive control over the release of oxygen and ROS, and the depletion of GSH. The simultaneous oxygen generation, in situ GSH depletion, and ROS overproduction play a synergetic role in sensitizing SDT toward hypoxic solid tumors, which is verified by the remarkable improvement of hypoxic environments and more significant growth inhibition of SDT against osteosarcoma both in vitro and in vivo, showing promising application in hypoxic solid tumor treatment.
机译：声动力疗法（SDT）是一种无创疗法，具有较高的人体穿透深度，在治疗深层实体瘤方面显示出巨大潜力。然而，SDT的功效受到实体瘤中普遍存在的缺氧的限制。鉴于此，通过将高铁酸盐（VI）和原卟啉IX集成到可生物降解的中孔介孔有机硅纳米平台中，然后组装月桂酸的相变材料，来开发超声激活的纳米系统。高铁酸盐（VI）与水以及肿瘤细胞中过表达的过氧化氢和谷胱甘肽（GSH）有效反应，导致肿瘤微环境独立的氧气产生和肿瘤中的原位GSH消耗。更重要的是，通过原卟啉增强的SDT和细胞内Fenton化学方法可同时实现显着的活性氧（ROS）过量生产。此外，超声引起的轻度高温会触发月桂酸的相变，从而实现对氧气和ROS释放以及GSH耗竭的超声响应控制。同时发生的氧气，原位GSH耗竭和ROS过量在使SDT对缺氧实体瘤敏感方面起着协同作用，这通过低氧环境的显着改善以及SDT对骨肉瘤的体内和体外生长抑制作用得到了明显的证实。在缺氧实体瘤治疗中显示出有希望的应用。

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  • 来源
    《Advanced Functional Materials》 |2019年第51期|1906195.1-1906195.16|共16页
  • 作者

    Fu Jingke; Li Tao; Zhu Yingchun; Hao Yongqiang;

  • 作者单位

    Shanghai Jiao Tong Univ Sch Med Shanghai Peoples Hosp 9 Dept Orthopaed Surg Shanghai Key Lab Orthopaed Implant Shanghai 200011 Peoples R China|Shanghai Jiao Tong Univ Sch Med Shanghai Peoples Hosp 9 Clin & Translat Res Ctr 3D Printing Technol Shanghai 200011 Peoples R China;

    Chinese Acad Sci Shanghai Inst Ceram Key Lab Inorgan Coating Mat Shanghai 200050 Peoples R China|Univ Chinese Acad Sci Ctr Mat Sci & Optoelect Engn Beijing 100049 Peoples R China;

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  • 原文格式 PDF
  • 正文语种 eng
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  • 关键词

    hypoxia; ROS; sonodynamic therapy; tumor microenvironment; tumor oxygenation;

    机译：缺氧ROS;声动力学治疗;肿瘤微环境肿瘤氧合;

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