Institute of Functional Nano and Soft Materials (FUNSOM), Jiangsu Key Laboratory for Carbon-Based Functional Materials and Devices, Collaborative Innovation Center of Suzhou Nano Science and Technology, Soochow University, Suzhou 215123, China.
J Am Chem Soc. 2023 May 24;145(20):11206-11214. doi: 10.1021/jacs.3c01156. Epub 2023 May 11.
The manipulation of the flexibility/rigidity of polymeric chains to control their function is commonly observed in natural macromolecules but largely unexplored in synthetic systems. Herein, we construct a series of protein-mimetic nano-switches consisting of a gold nanoparticle (GNP) core, a synthetic polypeptide linker, and an optically functional molecule (OFM), whose biological function can be dynamically regulated by the flexibility of the polypeptide linker. At the dormant state, the polypeptide adopts a flexible, random-coiled conformation, bringing GNP and OFM in close proximity that leads to the "turn-off" of the OFM. Once treated with alkaline phosphatase (ALP), the nano-switches are activated due to the increased separation distance between GNP and OFM driven by the coil-to-helix and flexible-to-rigid transition of the polypeptide linker. The nano-switches therefore enable selective fluorescence imaging or photodynamic therapy in response to ALP overproduced by tumor cells. The control over polymer flexibility represents an effective strategy to manipulate the optical activity of nano-switches, which mimics the delicate structure-property relationship of natural proteins.
聚合物链的柔韧性/刚性的操纵来控制其功能在天然大分子中很常见，但在合成系统中很大程度上尚未被探索。在此，我们构建了一系列由金纳米颗粒（GNP）核心、合成多肽连接子和光功能分子（OFM）组成的蛋白模拟纳米开关，其生物功能可以通过多肽连接子的柔韧性来动态调节。在休眠状态下，多肽采用灵活的无规卷曲构象，使 GNP 和 OFM 非常接近，导致 OFM 的“关闭”。一旦用碱性磷酸酶（ALP）处理，纳米开关就会被激活，因为 GNP 和 OFM 之间的距离由于多肽连接子的螺旋到卷曲和柔性到刚性的转变而增加。因此，纳米开关可以响应肿瘤细胞中过量产生的 ALP 进行选择性荧光成像或光动力治疗。对聚合物柔韧性的控制代表了一种操纵纳米开关光学活性的有效策略，它模仿了天然蛋白质的精细结构-性能关系。
