Hypoxia-Targeting, Tumor Microenvironment Responsive Nanocluster Bomb for Radical Enhanced Radiotherapy
Hypoxia-Targeting, Tumor Microenvironment Responsive Nanocluster Bomb for Radical Enhanced Radiotherapy
复制标题
用于根治性增强放射治疗的缺氧靶向肿瘤微环境响应纳米团簇炸弹
DOI：
10.1021/acsnano.7b04737
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发表时间：
2017-10-01
期刊：
影响因子：
17.1
通讯作者：
Hu, Yong
中科院分区：
文献类型：
--
作者：
Huo, Da;Liu, Sen;Hu, Yong
虽然超小金属纳米颗粒(NPs)已被用作放射增敏剂，以增强肿瘤组织的局部损伤，同时减少对周围器官的损伤，但它们在循环系统的快速清除和肿瘤内的缺氧继续阻碍其在放射治疗(RT)中的进一步应用。在这项研究中，我们报告了一种尺寸可调的纳米集束炸弹，初始尺寸约为33 nm-在血液循环中具有较长的半衰期，并被破坏以释放小的缺氧微环境靶向NPs(类似于6 mm)，以实现肿瘤的深度渗透。利用具有更高空间分辨率的NP增强CT精确成像实体肿瘤的低氧轮廓。一旦接受1064 nm激光的照射，CT引导下，肿瘤的局部光热消融和自由基物种的产生可以同时实现。诱导的自由基物种以Akt-mTOR途径依赖的方式缓解了低氧诱导的抵抗，并使肿瘤对放射的杀伤效果增敏。在原位乳腺癌和胰腺癌的动物模型上评估了治疗结果，支持了我们的联合治疗低氧肿瘤治疗的可行性。
Although ultrasmall metal nanoparticles (NPs) have been used as radiosensitizers to enhance the local damage to tumor tissues while reducing injury to the surrounding organs, their rapid clearance from the circulatory system and the presence of hypoxia within the tumor continue to hamper their further application in radiotherapy (RT). In this study, we report a size tunable nanocluster bomb with a initial size of approximately 33 nm-featuring a long half-life during blood circulation and destructed to release small hypoxia microenvironment-targeting NPs (similar to 6 mm) to achieve deep tumor penetration. Hypoxic profiles of solid tumors were precisely imaged using NP-enhanced 'computed tomography (CT) with higher spatial resolution. Once irradiated with,a 1064,nm laser, CT-guided, local photothermal ablation of the tumor and production of radical species could be achieved simultaneously. The induced radical species alleviated the hypoxia-induced resistance and sensitized the tumor to the killing efficacy of radiation in Akt-mTOR pathway-dependent manner. The therapeutic outcome was assessed in animal models of orthotopical breast cancer and pancreatic cancer, supporting the feasibility of our combinational treatment hypoxic tumor management.