Department of Materials, Department of Bioengineering and Institute for Biomedical Engineering, Imperial College London, London, SW7 2AZ, UK.
Adv Mater. 2017 Jul;29(26). doi: 10.1002/adma.201701086. Epub 2017 May 5.
Inspired by biological systems, many biomimetic methods suggest fabrication of functional materials with unique physicochemical properties. Such methods frequently generate organic-inorganic composites that feature highly ordered hierarchical structures with intriguing properties, distinct from their individual components. A striking example is that of DNA-inorganic hybrid micro/nanostructures, fabricated by the rolling circle technique. Here, a novel concept for the encapsulation of bioactive proteins in DNA flowers (DNF) while maintaining the activity of protein payloads is reported. A wide range of proteins, including enzymes, can be simultaneously associated with the growing DNA strands and Mg PPi crystals during the rolling circle process, ultimately leading to the direct immobilization of proteins into DNF. The unique porous structure of this construct, along with the abundance of Mg ions and DNA molecules present, provides many interaction sites for proteins, enabling high loading efficiency and enhanced stability. Further, as a proof of concept, it is demonstrated that the DNF can deliver payloads of cytotoxic protein (i.e., RNase A) to the cells without a loss in its biological function and structural integrity, resulting in highly increased cell death compared to the free protein.
受生物系统启发，许多仿生方法提出了用具有独特物理化学性质的功能材料进行制造。这些方法经常产生具有高度有序的分层结构的有机-无机复合材料，其特性与它们的单个组件明显不同。一个引人注目的例子是 DNA-无机杂化微/纳米结构，它是通过滚环技术制造的。在这里，报告了一种将生物活性蛋白封装在 DNA 花（DNF）中而保持蛋白有效负载活性的新概念。在滚环过程中，各种蛋白质，包括酶，可以同时与不断增长的 DNA 链和 MgPPi 晶体结合，最终导致蛋白质直接固定在 DNF 中。这种结构的独特多孔结构以及大量存在的 Mg 离子和 DNA 分子，为蛋白质提供了许多相互作用位点，从而实现了高负载效率和增强的稳定性。此外，作为概念验证，证明 DNF 可以将细胞毒性蛋白（即 RNase A）的有效负载递送到细胞中，而不会损失其生物学功能和结构完整性，与游离蛋白相比，细胞死亡显著增加。
