School of Nano-Tech and Nano-Bionics, University of Science and Technology of China, Hefei 230026, China.
CAS Key Laboratory of Nano-Bio Interface, Division of Nanobiomedicine, Suzhou Institute of Nano-Tech and Nano-Bionics, Chinese Academy of Sciences, Suzhou 215123, China.
Nano Lett. 2024 Jul 31;24(30):9406-9414. doi: 10.1021/acs.nanolett.4c02669. Epub 2024 Jul 22.
Extremely small iron oxide nanoparticle (ESIONP)-based stimuli-responsive switchable MRI contrast agents (CAs) show great promise for accurate detection of tumors due to their outstanding advantages of high specificity and low background signal. However, currently developed ESIONP-based switchable CAs often suffer single-biomarker-induced responses, which lack absolute specificity to pathological tissues, potentially diminishing diagnostic accuracy. In this study, weak acidity and hypoxia, two of the most remarkable characteristics of tumors, are introduced as dual biomarker stimuli to construct an ESIONP-based switchable MRI CA (DKL-CA), with its signal switch controlled by a "dual-key-and-lock" strategy. Only when DKL-CA is exposed to a coexisting weakly acidic and hypoxic environment can monodispersed ESIONPs form nanoclusters, thereby realizing a switch from the T to T contrast. Moreover, DKL-CA exhibits favorable biosafety and the capacity for precise tumor diagnosis in tumor-bearing mice. Overall, DKL-CA paves the way for designing highly accurate ESIONP-based MRI CAs for tumor diagnosis.
基于超小氧化铁纳米颗粒（ESIONP）的刺激响应型可切换磁共振成像对比剂（CA）因其高特异性和低背景信号的突出优势，有望准确检测肿瘤。然而，目前开发的基于 ESIONP 的可切换 CA 通常受到单一生物标志物诱导反应的影响，对病理组织缺乏绝对特异性，可能降低诊断准确性。在这项研究中，弱酸性和缺氧被引入作为双重生物标志物刺激，构建了基于 ESIONP 的可切换磁共振成像 CA（DKL-CA），其信号切换由“双钥匙-锁”策略控制。只有当 DKL-CA 暴露于共存的弱酸性和缺氧环境中时，单分散的 ESIONPs 才能形成纳米簇，从而实现从 T1 到 T2 对比的切换。此外，DKL-CA 表现出良好的生物安全性和在荷瘤小鼠中精确诊断肿瘤的能力。总体而言，DKL-CA 为设计用于肿瘤诊断的高精准基于 ESIONP 的磁共振成像 CA 铺平了道路。
