Imaging-guided focused ultrasound-induced thermal and sonodynamic effects of nanosonosensitizers for synergistic enhancement of glioblastoma therapy
Imaging-guided focused ultrasound-induced thermal and sonodynamic effects of nanosonosensitizers for synergistic enhancement of glioblastoma therapy
复制标题
成像引导聚焦超声诱导纳米声敏剂的热和声动力效应协同增强胶质母细胞瘤治疗
DOI：
10.1039/c9bm00292h
复制
发表时间：
2019-07-01
影响因子：
6.6
通讯作者：
Zheng, Hairong
中科院分区：
文献类型：
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作者：
Wan, Qian;Zou, Chao;Zheng, Hairong
胶质母细胞瘤(GBM)是一种预后差、死亡率高的致命性脑肿瘤。鉴于目前GBM治疗与传统手术、化疗和放射治疗相比疗效低、副作用严重，开发一种新的GBM治疗方法迫在眉睫。声动力疗法(SDT)因具有组织穿透深、生物安全性高等优点，在GBM治疗中受到广泛关注。然而，SDT的低ROS生成效率普遍限制了其进一步的应用和临床翻译。在这项工作中，我们报告了同时应用聚焦超声诱导的适度热疗(42℃)和SDT来协同增强对GBM的作用。采用组装法制备了锰离子(Mn2+)-人血清白蛋白(HSA)-六氯(Ce6)纳米组装体(HCM-Nas)作为靶向纳米声敏剂。我们的研究表明，HCM Nas的T-1加权对比性能(12.2 mm(-1)S(-1))优于临床使用的Magnevist(4.3 mm(-1)S(-1))，并在注射后24 h实现了高选择性的体外细胞识别和体内肿瘤靶向磁共振(MR)和荧光(FL)成像，信本比为13.5。在成像引导的聚焦超声照射下，肿瘤区域的温度和ROS含量随着时间的推移而同时增加，达到协同效应。在皮下移植的小鼠脑胶质瘤模型中，脑肿瘤被完全抑制，而在原位移植的小鼠脑胶质瘤模型中，其抗肿瘤效果显著提高。提示成像引导聚焦超声诱导的中温和SDT协同治疗是一种很有前途的治疗GMB的平台，具有很大的临床应用潜力。
Glioblastoma (GBM) is a deadly brain tumor with poor prognosis and high mortality in patients. Given the low efficacy and serious side effects of current GBM therapy compared to those of conventional surgery, chemotherapy and radiation therapy, the development of a novel method for GBM management is very urgent. Sonodynamic therapy (SDT) has gained considerable attention in GBM therapy due to the advantages of deep tissue penetration and high biosafety. However, the low reactive oxygen species (ROS) generation efficacy of SDT has generally limited further applications and clinical translation. In this work, we report the simultaneous application of focused ultrasound-induced moderate thermal treatment (42 degrees C) and SDT for synergistic enhancement against GBM. Manganese ion (Mn2+)-chelated human serum albumin (HSA)-chlorin e6 (Ce6) nanoassemblies (HCM NAs) as targeting nanosonosensitizers were prepared using an assembly strategy. Our studies indicated that the HCM NAs had excellent T-1-weighted contrast performance (12.2 mM(-1) s(-1)) compared to that of clinically used Magnevist (4.3 mM(-1) s(-1)) and achieved highly selective in vitro cell recognition and in vivo tumor-targeting magnetic resonance (MR) and fluorescence (FL) imaging with a signal-to-background ratio of 13.5 at 24 h post injection. Upon imaging-guided focused ultrasound irradiation, the temperature and reactive oxygen species (ROS) content of the tumor region increased simultaneously over time, achieving synergistic effects. The brain tumors were completely suppressed in subcutaneous mouse models of glioma, and the antitumor effect was greatly improved in orthotopic mouse models of glioma. It suggest that the synergistic treatment with moderate temperature and SDT induced by imaging-guided focused ultrasound is a promising platform against GMB, holds great potential in clinical settings.