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.
Bioconjug Chem. 2023 Sep 20;34(9):1622-1632. doi: 10.1021/acs.bioconjchem.3c00285. Epub 2023 Aug 16.
To realize the accurate diagnosis of tumors by magnetic resonance imaging (MRI), switchable magnetic resonance contrast agents (CAs) between T and T contrast enhancement that are constructed based on extremely small iron oxide nanoparticles (ESIONPs) have been developed in recent years. We herein report, for the first time, a novel ESIONP-based nanocluster (named EAmP), which exhibited hypoxia responsiveness to the tumor microenvironment and offered a T-to-T-switchable contrast enhancement function, effectively distinguishing between the normal tissue and tumor tissue. In detail, active perfluorophenyl ester-modified ESIONPs with a diameter of approximately 3.6 nm were initially synthesized, and then 4,4'-azodianiline was used as a cross-linker to facilitate the formation of nanoclusters from ESIONPs through the reaction between the active ester and amine. Finally, poly(ethylene glycol) was further modified onto nanoclusters by utilizing the remaining active ester residues. The resulting EAmP demonstrated satisfactory colloidal stability and favorable biosafety and exhibited a desired T-to-T-switchable function, as evidenced by conversion from nanocluster to the dispersed state and a significant decrease in the / ratio from 14.86 to 1.61 when exposed to a mimical hypoxic environment in the solution. Moreover, EAmP could decompose into dispersed ESIONPs at the tumor region, resulting in a switch from T to T contrast enhancement. This T-to-T-switchable contrast agent offers high sensitivity and signal-to-noise ratio to realize the accurate diagnosis of tumors. In conclusion, hypoxia-responsive EAmP is a potential MRI nanoprobe for improving the diagnostic accuracy of solid tumors.
为了通过磁共振成像（MRI）实现肿瘤的准确诊断，近年来基于超小氧化铁纳米粒子（ESIONP）构建了可在 T 和 T 造影增强之间切换的磁共振对比剂（CA）。在此，我们首次报道了一种新型基于 ESIONP 的纳米簇（命名为 EAmP），它表现出对肿瘤微环境的缺氧响应，并提供了 T 到 T 的可切换对比增强功能，有效地将正常组织与肿瘤组织区分开来。具体而言，首先合成了直径约 3.6nm 的活性全氟苯基酯修饰的 ESIONP，然后使用 4,4'-偶氮二苯胺作为交联剂，通过活性酯和胺之间的反应促进 ESIONP 形成纳米簇。最后，通过利用剩余的活性酯残基，将聚乙二醇进一步修饰到纳米簇上。所得的 EAmP 表现出令人满意的胶体稳定性和良好的生物安全性，并表现出所需的 T 到 T 的可切换功能，这表现为在溶液中暴露于模拟缺氧环境时，从纳米簇转化为分散状态以及从 14.86 降至 1.61。此外，EAmP 可以在肿瘤部位分解为分散的 ESIONP，从而导致 T 到 T 的对比增强转换。这种 T 到 T 的可切换对比剂具有高灵敏度和信噪比，可以实现肿瘤的准确诊断。总之，缺氧响应的 EAmP 是一种提高实体瘤诊断准确性的潜在 MRI 纳米探针。
