Enzyme-instructed supramolecular assemblies promote intracellular boron accumulation for boron neutron capture therapy
Enzyme-instructed supramolecular assemblies promote intracellular boron accumulation for boron neutron capture therapy
复制标题
酶引导的超分子组装体促进细胞内硼积累，用于硼中子捕获疗法
DOI：
10.1088/1361-6528/ac15ca
复制
发表时间：
2021
期刊：
影响因子：
3.5
通讯作者：
Yuan Gao
中科院分区：
文献类型：
--
作者：
Qingxin Yao;Chengling Wu;Jiali Chen;Yan Zhao;Yuan Gao
硼剂在癌细胞中的选择性积累对于 BNCT 至关重要。在这里，我们涉及酶指导的超分子组装（EISA），以促进典型硼剂硼基苯丙氨酸（BPA）在癌细胞中的积累。通过将 BPA 与磷酸化组装前体共价结合，含硼前体经历磷酸酶催化的去磷酸化，产生组装分子，然后自组装形成纳米材料。由于癌细胞磷酸酶活性上调，动力学偏好允许 EISA 选择性地在 HeLa 细胞中积累硼。有趣的是，通过将BPA附着在前体的主链或侧链上，含硼异构体表现出不同的组装倾向以及随时间变化的形态变化，从而导致硼在细胞内的分化积累。总体而言，与 BPA 相比，优化的含硼组装前体可以显着提高癌细胞中硼的积累。在这项研究中，我们展示了一种将硼剂引入癌细胞的便捷方法。我们预计 EISA 介导的硼积累将有助于设计硼剂以促进 BNCT 治疗。
Selective accumulation of boron agents in cancer cells is of critical importance for BNCT. Here we involve enzyme-instructed supramolecular assembly (EISA) to facilitate the accumulation of a typical boron agent borylphenylalanine (BPA) in cancer cells. By covalently conjugating BPA to the phosphorylated assembly precursor, the boron-bearing precursors undergo phosphatase-catalyzed dephosphorylation to yield assembly molecules, which then self-assemble to form nanomaterials. Due to the up-regulated phosphatase activity of cancer cells, kinetic preference allows the EISA to accumulate boron in HeLa cells selectively. Interestingly, by attaching BPA on the backbone or side-chain of precursor, the boron-bearing isomers show different assembly propensity with time-dependent morphology change, which leads to the differentiated accumulation of boron inside cells. Overall, the optimized boron-bearing assembly precursor could significantly improve the boron accumulation compared with BPA in cancer cells. In this study, we have demonstrated a convenient method to introduce boron agents to cancer cells. We envision that the EISA-mediated accumulation of boron will be helpful in the design of boron agents to facilitate BNCT treatment.