Bioinspired Cell Nuclear Nanotransporters Generated by Self-Assembly of Amphiphilic Polysaccharide-Amino Acid Derivatives Conjugates
Bioinspired Cell Nuclear Nanotransporters Generated by Self-Assembly of Amphiphilic Polysaccharide-Amino Acid Derivatives Conjugates
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DOI：
10.1002/adbi.201900189
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发表时间：
2019-11-26
影响因子：
4.1
通讯作者：
Ono, Kimika
中科院分区：
文献类型：
--
作者：
Nagahama, Koji;Sano, Yoshinori;Ono, Kimika
纳米材料的发展肯定会将功能生物大分子和生物活性合成化合物输送到细胞核中，这肯定会为核靶向新技术的产生带来希望。然而，核运输纳米材料的发展仍然是一个巨大的挑战，因为真核细胞的细胞质和核之间的分子运输受到通过核膜的唯一门户--核孔复合体(NPC)的严格调控。在这里，展示了新型人工核纳米转运体(NucPorters)的合理设计，灵感来自于进口，自然发生的核转运体。NucPorter是通过简单的分子设计产生的：两亲性聚合物的自组装，其中几个带有苯基的疏水氨基酸衍生物连接到带负电荷的亲水性肝素。NucPorter可以模仿进口机器通过NPC的基本结构和化学特征。重要的是，NucPorter在培养的细胞、组织/器官和活着的小鼠中展示了显著的快速和高效的核运输。此外，NucPorter成功地将酶和合成抗癌药物导入细胞核，同时保持其生物活性。因此，NucPorter为生产创新的核靶向药物、诊断、细胞成像和工程技术以及药物输送系统提供了一条很有前途的新途径。
Development of nanomaterials that surely transport functional biomacromolecules and bioactive synthetic compounds into the cell nucleus must be promising for the generation of nuclear-targeting new technologies. However, the development of nuclear transporting nanomaterials thus still remains a significant challenge, because molecular transport between the cytoplasm and the nucleus of a eukaryotic cell is strictly regulated by the sole gateway through the nuclear envelope, the nuclear pore complexes (NPCs). Here, the rational design of novel artificial nuclear nanotransporters (NucPorters), inspired by importin, naturally occurring nuclear transporters is shown. The NucPorter is generated by simple molecular design: self-assembly of amphiphilic polymers, where a few numbers of hydrophobic amino-acid derivatives with phenyl groups are conjugated to negatively charged hydrophilic heparin. The NucPorter can mimic essential structural and chemical features of importin machinery to pass through the NPCs. Importantly, the NucPorter demonstrates remarkable rapid and high efficient nuclear transport in cultured cells, tissue/organ, and living mice. Moreover, the NucPorter successfully imports both enzymes and synthetic anticancer drugs into the nucleus while maintaining their bioactivity. Thus, the NucPorter provides a promising new route to generate innovative nuclear-targeting medicines, diagnostics, cell imaging and engineering techniques, and drug delivery systems.