Department of Biomaterials, Key Laboratory of Biomedical Engineering of Fujian Province, College of Materials, Xiamen University, Xiamen, Fujian, 361005, China.
Center of Materials Science and Optoelectronics Engineering, University of Chinese Academy of Sciences, Beijing, 100049, China.
Adv Mater. 2020 Jan;32(4):e1906799. doi: 10.1002/adma.201906799. Epub 2019 Dec 4.
Metastasis remains the major cause of death in cancer patients. Thus, there is a need to sensitively detect tumor metastasis, especially ultrasmall metastasis, for early diagnosis and precise treatment of cancer. Herein, an ultrasensitive T -weighted magnetic resonance imaging (MRI) contrast agent, UMFNP-CREKA is reported. By conjugating the ultrasmall manganese ferrite nanoparticles (UMFNPs) with a tumor-targeting penta-peptide CREKA (Cys-Arg-Glu-Lys-Ala), ultrasmall breast cancer metastases are accurately detected. With a behavior similar to neutrophils' immunosurveillance process for eliminating foreign pathogens, UMFNP-CREKA exhibits a chemotactic "targeting-activation" capacity. UMFNP-CREKA is recruited to the margin of tumor metastases by the binding of CREKA with fibrin-fibronectin complexes, which are abundant around tumors, and then release of manganese ions (Mn ) to the metastasis in response to pathological parameters (mild acidity and elevated H O ). The localized release of Mn and its interaction with proteins affects a marked amplification of T -weighted magnetic resonance (MR) signals. In vivo T -weighted MRI experiments reveal that UMFNP-CREKA can detect metastases at an unprecedented minimum detection limit of 0.39 mm, which has significantly extended the detection limit of previously reported MRI probe.
转移仍然是癌症患者死亡的主要原因。因此，需要灵敏地检测肿瘤转移，特别是超小转移，以便对癌症进行早期诊断和精确治疗。在此，报道了一种超灵敏 T 加权磁共振成像（MRI）造影剂 UMFNP-CREKA。通过将超小的锰铁氧化物纳米颗粒（UMFNPs）与肿瘤靶向五肽 CREKA（半胱氨酸-精氨酸-谷氨酸-赖氨酸-丙氨酸）缀合，可以准确检测超小乳腺癌转移。与中性粒细胞免疫监视过程消除外来病原体的行为类似，UMFNP-CREKA 表现出趋化性“靶向-激活”能力。UMFNP-CREKA 通过 CREKA 与纤维蛋白-纤维连接蛋白复合物的结合被募集到肿瘤转移的边缘，该复合物在肿瘤周围丰富，然后响应病理参数（轻度酸度和升高的 H O ）向转移释放锰离子（Mn ）。局部释放的 Mn 及其与蛋白质的相互作用会影响 T 加权磁共振（MR）信号的显著放大。体内 T 加权 MRI 实验表明，UMFNP-CREKA 可以以前所未有的最低检测极限 0.39mm 检测转移，这大大扩展了之前报道的 MRI 探针的检测极限。
