Biomolecular robotics for chemomechanically driven guest delivery fuelled by intracellular ATP
Biomolecular robotics for chemomechanically driven guest delivery fuelled by intracellular ATP
复制标题
DOI：
10.1038/nchem.1681
复制
发表时间：
2013-07-01
期刊：
影响因子：
21.8
通讯作者：
Aida, Takuzo
中科院分区：
文献类型：
--
作者：
Biswas, Shuvendu;Kinbara, Kazushi;Aida, Takuzo
在纳米医学中，为了诊断和治疗的目的，正在积极开发能够在感应到特定生物信号时选择性地释放客体分子的纳米载体。在这里，我们报告了一种基于蛋白质的纳米载体，它在细胞内存在三磷酸腺苷(ATP)的情况下开放。这种纳米载体由多个桶形伴侣单元组成，通过与镁离子的配合组装成管状结构，保护客体分子免受生物降解。当其表面用硼酸衍生物功能化时，纳米载体能够进入细胞。细胞内的ATP水解为腺苷-5‘-二磷酸(ADP)导致伴侣单位的构象变化，进而产生机械力，导致管子的解体和客体的释放。这种断裂的发生与ATP浓度呈S形关系，这意味着纳米载体可以根据选择性客体释放的ATP浓度来区分生物环境。此外，生物分布测试显示纳米载体在肿瘤组织中优先积累。
The development of nanocarriers that selectively release guest molecules on sensing a particular biological signal is being actively pursued in nanomedicine for diagnostic and therapeutic purposes. Here we report a protein-based nanocarrier that opens in the presence of intracellular adenosine-5'-triphosphate (ATP). The nanocarrier consists of multiple barrel-shaped chaperonin units assembled through coordination with Mg2+ into a tubular structure that protects guest molecules against biological degradation. When its surface is functionalized with a boronic acid derivative, the nanocarrier is able to enter cells. The hydrolysis of intracellular ATP into adenosine-5'-diphosphate (ADP) induces conformational changes of the chaperonin units, which in turns generate a mechanical force that leads to the disassembly of the tube and release of the guests. This scission occurs with a sigmoidal dependence on ATP concentration, which means that the nanocarrier can differentiate biological environments in terms of the concentration of ATP for selective guest release. Furthermore, biodistribution tests reveal preferential accumulation of the nanocarriers in a tumour tissue.