Targeted Magnetic Resonance Imaging and Modulation of Hypoxia with Multifunctional Hyaluronic Acid-MnO2 Nanoparticles in Glioma
Targeted Magnetic Resonance Imaging and Modulation of Hypoxia with Multifunctional Hyaluronic Acid-MnO2 Nanoparticles in Glioma
复制标题
胶质瘤中多功能透明质酸-MnO2纳米颗粒的靶向磁共振成像和缺氧调节
DOI：
10.1002/adhm.201900047
复制
发表时间：
2019-05-23
影响因子：
10
通讯作者：
Zhang, Li Ming
中科院分区：
文献类型：
--
作者：
Fu, Chaoping;Duan, Xiaohui;Zhang, Li Ming
二氧化锰(MnO2)纳米粒子是一种很有前途的肿瘤微环境响应性纳米消融载体，可用于靶向磁共振成像(MRI)和缓解肿瘤缺氧。然而，目前常用的合成方法的复杂性和潜在的毒性限制了它们的临床应用。本文采用一种简单的方法合成了多功能透明质酸-二氧化锰纳米颗粒(HA-MnO2 NPs)，它既是一种还原剂，又是一种表面包覆材料。得到的HA-MnO2纳米粒子具有良好的水分散性、良好的胶体稳定性、低毒以及对肿瘤微环境(高过氧化氢和高谷胱甘肽，低pH)的响应性。静脉注射后，HA-MnO2纳米粒子对大鼠脑胶质瘤的MRI检测显示出高的成像灵敏度，最长可达3d。这些纳米粒子也有效地缓解了大鼠脑胶质瘤模型的肿瘤缺氧。血管内皮生长因子和缺氧诱导因子-1α在脑胶质瘤中的表达下调，证实了HA-MnO2纳米粒对肿瘤缺氧的持续抑制作用。这些结果表明，HA-MnO2纳米颗粒可以用于灵敏的、靶向的胶质瘤MRI检测，同时可以减少肿瘤的缺氧。
Manganese dioxide (MnO2)-based nanoparticles are a promising tumor microenvironment-responsive nanotheranostic carrier for targeted magnetic resonance imaging (MRI) and for alleviating tumor hypoxia. However, the complexity and potential toxicity of the present common synthesis methods limit their clinical application. Herein, multifunctional hyaluronic acid-MnO2 nanoparticles (HA-MnO2 NPs) are synthesized in a simple way by directly mixing sodium permanganate with HA aqueous solutions, which serve as both a reducing agent and a surface-coating material. The obtained HA-MnO2 NPs show an improved water-dispersibility, fine colloidal stability, low toxicity, and responsiveness to the tumor microenvironment (high H2O2 and high glutathione, low pH). After intravenous injection, HA-MnO2 NPs exhibit a high imaging sensitivity for detecting rat intracranial glioma with MRI for a prolonged period of up to 3 d. These nanoparticles also effectively alleviate the tumor hypoxia in a rat model of intracranial glioma. The downregulation of VEGF and HIF-1 alpha expression in intracranial glioma validates the sustained attenuation effect of HA-MnO2 NPs on tumor hypoxia. These results show that HA-MnO2 NPs can be used for sensitive, targeted MRI detection of gliomas and simultaneous attenuation of tumor hypoxia.