MOE Key Laboratory of Biomedical Engineering, College of Biomedical Engineering and Instrument Science , Zhejiang University , Hangzhou 310058 , China.
Center for Nanoparticle Research , Institute for Basic Science (IBS) , Seoul 08826 , Republic of Korea.
Nano Lett. 2019 Jul 10;19(7):4213-4220. doi: 10.1021/acs.nanolett.8b04411. Epub 2019 Feb 14.
Smart magnetic resonance (MR) contrast agents, by which MR contrast can be selectively enhanced under acidic tumor microenvironment, are anticipated to significantly improve the diagnostic accuracy. Here, we report pH-sensitive iron oxide nanoparticle assemblies (IONAs) that are cross-linked by small-molecular aldehyde derivative ligands. The dynamic formation and cleavage of hydrazone linkages in neutral and acidic environments, respectively, allow the reversible response of the nanoassemblies to pH variations. At neutral pH, IONAs are structurally robust due to the cross-linking by the strong hydrazone bonds. In acidic tumor microenvironment, the hydrazone bonds are cleaved so that the IONAs are quickly disassembled into a large number of hydrophilic extremely small-sized iron oxide nanoparticles (ESIONs). As a result, significantly enhanced T1MR contrast is achieved, as confirmed by the measurement of 1 values at different pH conditions. Such acidity-targeting MR signal amplification by the pH-sensitive IONAs was further validated in vivo, demonstrating a novel T1 magnetic resonance imaging (MRI) strategy for highly sensitive imaging of acidic tumors.
智能磁共振（MR）对比剂可在酸性肿瘤微环境下选择性增强 MR 对比，有望显著提高诊断准确性。在这里，我们报告了由小分子醛衍生物配体交联的 pH 敏感氧化铁纳米颗粒组装体（IONAs）。在中性和酸性环境中，腙键的动态形成和裂解分别允许纳米组装体对 pH 值变化的可逆响应。在中性 pH 下，由于强腙键的交联，IONAs 的结构非常坚固。在酸性肿瘤微环境中，腙键被切断，使得 IONAs 迅速解组装成大量亲水性的超小尺寸氧化铁纳米颗粒（ESIONs）。因此，通过在不同 pH 条件下测量 1 值，证实了 T1MR 对比得到了显著增强。通过体内实验进一步验证了这种由 pH 敏感的 IONAs 引起的靶向 MR 信号放大，为酸性肿瘤的高灵敏度成像提供了一种新的 T1 磁共振成像（MRI）策略。
