Ultrasensitive MRI detection of spontaneous pancreatic tumors with nanocage-based targeted contrast agent
Ultrasensitive MRI detection of spontaneous pancreatic tumors with nanocage-based targeted contrast agent
复制标题
DOI：
10.1016/j.biomaterials.2017.10.029
复制
发表时间：
2018-01-01
期刊：
影响因子：
14
通讯作者：
Hashizume, Makoto
中科院分区：
文献类型：
--
作者：
Kawano, Takahito;Murata, Masaharu;Hashizume, Makoto
磁共振成像（MRI）诊断胰腺癌需要特异性和敏感性更高的造影剂。在这项研究中，基于小热休克蛋白16.5 （Hsp16.5）的纳米笼与钆（III）螯合造影剂和iRGD肽（靶向胰腺癌细胞上表达的neuropilin-1）结合。为了研究模板尺寸是否影响弛豫度，设计了具有1 - 4个疏水结构域的纳米笼。MRI数据显示，较大的纳米笼比较小的纳米笼具有更高的Ti弛豫率，这是由于纳米笼尺寸的增加导致分子翻滚速率的降低，以及引入疏水结构域导致的坚固的笼结构。对于体内MRI研究，使用KrasG72D对工程纳米笼进行评估；Trp53 (R172H);Pdx-1Cre （KPC）转基因小鼠模型，在正常血管生成、免疫功能和炎症过程下发生临床相关的胰腺肿瘤。在KPC基因工程小鼠模型中，利用蛋白质纳米笼的分子MRI可以检测到neuropilin-1阳性细胞，并对自发性胰腺肿瘤产生强烈的信号增强。新型irgd修饰的纳米笼显示出作为胰腺肿瘤诊断特异性和敏感性MRI造影剂的潜力，可用于临床翻译。(C) 2017 Elsevier Ltd.版权所有。
Contrast agents with greater specificity and sensitivity are required for the diagnosis of pancreatic cancers by magnetic resonance imaging (MRI). In this study, small heat shock protein 16.5 (Hsp16.5)based nanocages conjugated to gadolinium(III)-chelated contrast agents and iRGD peptides (which target neuropilin-1 expressed on pancreatic cancer cells) were developed. To investigate whether template size influences relaxivity, nanocages with one to four hydrophobic domains were designed. MRI data showed that larger nanocages had higher Ti relaxivity than smaller nanocages, which resulted from a reduction in molecular tumbling rates caused by an increase in nanocage size, and a robust cage structure resulting from the introduction of hydrophobic domains. For in vivo MRI studies, the engineered nanocages were evaluated using the KrasG72D; Trp53(R172H); Pdx-1Cre (KPC) transgenic mouse models, which develop clinically relevant pancreatic tumor under normal processes of angiogenesis, immune function and inflammation. Molecular MRI with protein nanocages was enabled to detect neuropilin-1-positive cells and to produce strong signal enhancement of spontaneous pancreatic tumors in KPC genetically engineered mouse models. Novel iRGD-modified nanocages displayed potential as a specific and sensitive MRI contrast agent for the diagnosis of pancreatic tu, mors for clinical translation. (C) 2017 Elsevier Ltd. All rights reserved.