Multiplexed 129Xe HyperCEST MRI detection of genetically-reconstituted bacterial protein nanoparticles in human cancer cells
Multiplexed 129Xe HyperCEST MRI detection of genetically-reconstituted bacterial protein nanoparticles in human cancer cells
复制标题
多重 129Xe HyperCEST MRI 检测人类癌细胞中基因重组细菌蛋白纳米粒子
DOI：
10.1101/599118
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发表时间：
2019
期刊：
影响因子：
--
通讯作者：
Tomonobu M. Watanabe
中科院分区：
文献类型：
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作者：
Ryota Mizushima;Kanako Inoue;Atsuko H. Iwane;Atsuomi Kimura;Tomonobu M. Watanabe
气体囊泡纳米颗粒（GVS）是在细菌和古细菌中表达的含气体蛋白质组装体。最近，GV作为MRI和超声检查的可遗传编码造影剂在生物技术应用中获得了相当大的关注。然而，目前，GVs的实际使用受到缺乏用于将其诱导到哺乳动物细胞中的稳健方法的阻碍。在这里，我们证明了蛋白质纳米颗粒的遗传重建，其特征性双锥结构类似于人类乳腺癌细胞系KPL-4中的天然GV，并通过克隆到Tol 2转座子载体中的人源化气泡基因的减少集的表达对其大小和形状进行遗传控制，参考了蓝细菌红毛藻/琼脂糖的天然气泡基因簇。然后，我们报告了这些纳米粒子作为超极化氙化学交换饱和转移（HyperCEST）MRI的多路复用，敏感和遗传编码造影剂的效用。
Gas vesicle nanoparticles (GVs) are gas‐containing protein assemblies expressed in bacteria and archaea. Recently, GVs have gained considerable attention for biotechnological applications as genetically encodable contrast agents for MRI and ultrasonography. However, at present, the practical use of GVs is hampered by a lack of robust methodology for their induction into mammalian cells. Here, we demonstrate the genetic reconstitution of protein nanoparticles with characteristic bicone structures similar to natural GVs in a human breast cancer cell line KPL‐4 and genetic control of their size and shape through expression of reduced sets of humanized gas vesicle genes cloned into Tol2 transposon vectors, referencing the natural gas vesicle gene clusters of the cyanobacteriaplanktothrix rubescens/agardhii. We then report the utility of these nanoparticles as multiplexed, sensitive, and genetically encoded contrast agents for hyperpolarized xenon chemical exchange saturation transfer (HyperCEST) MRI.