CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety and CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology of China, Beijing 100190, People's Republic of China.
Research Unit of Nanoscience and Technology, Chinese Academy of Medical Sciences, Beijing 100021, People's Republic of China.
J Am Chem Soc. 2021 Feb 3;143(4):1846-1853. doi: 10.1021/jacs.0c10245. Epub 2021 Jan 4.
Hypoxia is a common phenomenon among most solid tumors that significantly influences tumor response toward chemo- and radiotherapy. Understanding the distribution and extent of tumor hypoxia in patients will be very important to provide personalized therapies in the clinic. Without sufficient vessels, however, traditional contrast agents for clinical imaging techniques will have difficulty in accumulating in the hypoxic region of solid tumors, thus challenging the detection of hypoxia To overcome this problem, herein we develop a novel hypoxia imaging probe, consisting of a hypoxia-triggered self-assembling ultrasmall iron oxide (UIO) nanoparticle and assembly-responding fluorescence dyes (NBD), to provide dual-mode imaging . In this strategy, we have employed nitroimidazole derivatives as the hypoxia-sensitive moiety to construct intermolecular cross-linking of UIO nanoparticles under hypoxia, which irreversibly form larger nanoparticle assemblies. The hypoxia-triggered performance of UIO self-assembly not only amplifies its -weighted MRI signal but also promotes the fluorescence intensity of NBD through its emerging hydrophobic environment incorporated into self-assemblies. results further confirm that our hypoxic imaging probe can display a prompt MRI signal for the tumor interior region, and its signal enhancement performs a long-term effective feature and gradually reaches 3.69 times amplification. Simultaneously, this probe also exhibits obvious green fluorescence in the hypoxic region of tumor sections. Accordingly, we also have developed a MRI difference value method to visualize the 3D distribution and describe the extent of the hypoxic tumor region within the whole bodies of mice. Due to its notable efficiency of penetration and accumulation inside a hypoxic tumor, our hypoxia imaging probe could also be considered as a potential candidate as a versatile platform for hypoxia-targeted drug delivery, and meanwhile its hypoxia-related therapeutic efficacy can be monitored.
缺氧是大多数实体瘤中常见的现象，它显著影响肿瘤对化疗和放疗的反应。了解患者肿瘤缺氧的分布和程度对于在临床上提供个体化治疗非常重要。然而，由于缺乏足够的血管，传统的临床成像技术的造影剂很难在实体瘤的缺氧区域积累，从而难以检测缺氧。为了解决这个问题，我们开发了一种新型的缺氧成像探针，由缺氧触发的自组装超小氧化铁（UIO）纳米粒子和组装响应的荧光染料（NBD）组成，提供双模成像。在该策略中，我们采用硝基咪唑衍生物作为缺氧敏感部分，在缺氧下构建 UIO 纳米粒子的分子间交联，不可逆地形成更大的纳米粒子组装体。UIO 自组装的缺氧触发性能不仅放大了其 T2 加权 MRI 信号，还通过其形成的疏水环境促进了 NBD 的荧光强度。结果进一步证实，我们的缺氧成像探针可以对肿瘤内部区域显示出快速的 MRI 信号，并且其信号增强具有长期有效的特征，并逐渐达到 3.69 倍的放大。同时，该探针在肿瘤切片的缺氧区域也表现出明显的绿色荧光。因此，我们还开发了一种 MRI 差值法来可视化缺氧肿瘤区域的 3D 分布，并描述小鼠全身缺氧肿瘤区域的程度。由于其在缺氧肿瘤内部具有显著的渗透和积累效率，我们的缺氧成像探针也可以被认为是缺氧靶向药物输送的多功能平台的潜在候选物，同时可以监测其与缺氧相关的治疗效果。
