缺氧引發的超小氧化鐵納米粒子自組裝可放大腫瘤成像信號
作者：
小柯機器人發布時間：2021/1/7 13:51:30
國家納米中心陳春英課題組發現，缺氧觸發的超小氧化鐵納米粒子自組裝可放大腫瘤的成像信號。該研究於2021年1月4日發表於國際一流學術期刊《美國化學會志》。
研究人員表示，缺氧是大多數實體瘤中常見的現象，並會嚴重影響腫瘤對化學療法和放射療法的反應。了解患者體內腫瘤缺氧的分布和程度對於在臨床上提供個性化療法非常重要。但是，如果沒有足夠的血管，用於臨床成像技術的傳統造影劑將很難在實體瘤的缺氧區域中積聚，從而挑戰了體內缺氧的檢測。
為了克服這個問題，研究人員開發了一種新型的缺氧成像探針，該探針由缺氧觸發的自組裝超小氧化鐵（UIO）納米粒子和與組裝相對應的螢光染料（NBD）組成，從而可提供體內雙模式成像。在這種策略中，研究人員採用了硝基咪唑衍生物作為缺氧敏感部分，可在缺氧條件下構建UIO納米粒子的分子間交聯，而後者不可逆地形成更大的納米粒子組件。UIO自組裝的缺氧觸發性能不僅放大了其T2加權MRI信號，而且通過其結合到自組裝中的新興疏水環境而提高了NBD的螢光強度。
體內結果進一步證實，這個缺氧成像探針可以顯示針對腫瘤內部區域的即時MRI信號，並且其信號增強作用具有長期有效的功能並逐漸達到3.69倍的放大倍數。同時，該探針在腫瘤切片的缺氧區域也顯示出明顯的綠色螢光。因此，研究人員還開發了一種MRI差值方法來可視化3D分布並描述了小鼠體內缺氧腫瘤區域的範圍。由於其在缺氧腫瘤中的穿透和積累效率顯著，這個缺氧成像探針也可能成為缺氧靶向藥物遞送的多功能平臺，並同時可以監測其與缺氧相關的治療功效。
附：英文原文
Title: Hypoxia-Triggered Self-Assembly of Ultrasmall Iron Oxide Nanoparticles to Amplify the Imaging Signal of a Tumor
Author: Huige Zhou, Mengyu Guo, Jiayang Li, Fenglan Qin, Yuqing Wang, Tao Liu, Jing Liu, Zeinab Farhadi Sabet, Yaling Wang, Ying Liu, Qing Huo, Chunying Chen
Issue&Volume: January 4, 2021
Abstract: 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 in vivo. 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 vivo. 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 T2-weighted MRI signal but also promotes the fluorescence intensity of NBD through its emerging hydrophobic environment incorporated into self-assemblies. In vivo 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.
DOI: 10.1021/jacs.0c10245
Source: https://pubs.acs.org/doi/10.1021/jacs.0c10245