Nature Material：科学家用人造DNA制成生物凝胶胶囊
美国康奈尔大学研究人员应用人工合成的十字形，Y形，T型DNA制成生物相容，可降解的廉价凝胶，这种凝胶能很容易的被制成各种需要的形状，用于生物医学领域。
凝胶是一种由长链分子彼此结合形成的液体状或半固体物质，它们结构上存在小的空隙，能像海绵一样吸收水或其它液体。如果吸收的是药物，凝胶可以随着自身的生物降解而逐步释放药物。凝胶还被用于组织工程和组织修复，因为空隙里可能吸收有干细胞，组织生长因子等。
这些凝胶通常由有机或无机聚合物构成，譬如藻酸盐。有些还由蛋白质形成，但是不会完全从生物DNA得到。凝胶形成条件包括有机溶液，酸以及高温，这对药物和活细胞很不利，所以必须在凝胶形成后才注入这些物质。
而康奈尔生物和环境工程助理教授Dan Luo发明了不需要以上条件的方法。所以在凝胶形成前药物就可以被注入。凝胶完全由人工合成DNA构成，不会引起免疫反应，因此可以携带蛋白质甚至活细胞。
研究结果发表在9月24号网络版《Nature Material》上，并将刊登在最近的印刷本上。
DNA的序列决定了彼此符合的两条链才能结合。Luo通过让DNA上的一部分彼此符合，制造出了树状结构。制造凝胶时，通过连接酶的作用，十字形DNA连接成立方体三维结构，Y形DNA则先形成六角形结构，再构成三维凝胶，T形DNA是随机组合。
研究人员发现，通过改变DNA种类和浓度，他们可以容易的改变凝胶的特性，如硬度和吸收性等。为了验证凝胶保持形状的能力，科学家们将它们制成各种形式，如在纳米级别上的“CORNELL”字样。
为了测试DNA凝胶携带药物的能力，他们将猪胰岛素和抗癌物质喜树碱注入这种“胶囊”，然后观察释放情况。当携带活细胞时，3天后细胞仍然未失去活性。研究人员表示，酶破坏DNA结构后，其中的细胞仍然是活的。
英文原文：
Synthetic DNA Makes Better Hydrogels for Drug Delivery
Using synthetic DNA formed into crosses, Y's and T's, Cornell researchers have created biocompatible, biodegradable, inexpensive hydrogels that can be easily formed into any desired shape for biomedical applications.
Hydrogels are liquid or semisolid materials composed of long-chain molecules cross-linked to one another to create many small empty spaces that can absorb water or other liquids like a sponge. If the spaces are filled with a drug, the hydrogel can dispense the drug gradually as the structure biodegrades. Widespread research also is under way on using hydrogels as scaffolds for tissue engineering and tissue repair, where the spaces in the gel might be filled with stem cells, tissue-growth factors or a combination of both.
Hydrogels for these purposes are usually made from organic or inorganic polymers (molecules that form long chains), such as alginate from seaweed. Some have been made from proteins but none entirely from ordinary DNA. So far, all these processes have used organic solvents or acids or involve high temperatures, making conditions too harsh for a drug or living cells, so the materials to be encapsulated must be loaded in afterward.
The new process, developed in the laboratory of Dan Luo, Cornell assistant professor of biological and environmental engineering, uses no high temperatures or harsh chemicals, so the material to be encapsulated in the gel can be introduced before the gel is formed. Because the gel is made of only synthetic DNA, no immune response should be triggered, the researchers said, so the material encapsulated can include proteins and even live mammalian cells.
The research was published Sept. 24 in the online version of Nature Materials and will appear in a forthcoming print issue of the journal.
A DNA molecule is a long chain in a sequence that is unique to each chain. Conveniently, two chains with complementary sequences can lock onto one another like two halves of a zipper. By making synthetic DNA chains whose sequences are complementary over only part of their length, Luo and colleagues have created tree-shaped structures.
To create hydrogels, they made branched DNA that formed itself into crosses, Y's and T's with "sticky" ends that could link to each other with the help of enzymes known as ligases. The cross-shaped branched DNA forms a gel by linking together into sheets of tiny squares that tangle in three dimensions; Y shapes form hexagonal structures like a chain link fence that combine into a fibrous three-dimensional form, while T shapes create random, disorganized patterns that look like an assembly of scales.
The researchers found that they could easily alter certain properties of the resulting gelatinous materials, including rigidity and absorbency, by adjusting the types of branched DNA used and the concentration of DNA in the mix. To demonstrate the ability of some of the materials to hold their shape, the researchers created them in a variety of different molds, including some that spelled out "CORNELL" at centimeter and nanoscales.
To test the use of the DNA hydrogels for delivering drugs, the researchers encapsulated porcine insulin and the anticancer drug Camptothecin and observed that the drugs were released in a controlled manner over time. When they encapsulated live cells in a gel, they found that the cells were still alive three days later. It is possible, the researchers said, that live cells encapsulated in a DNA hydrogel could be recovered, still alive, by breaking down the DNA structure with enzymes.
Co-authors with Luo are Cornell graduate students Soong Ho Um, Jong Bum Lee and Sang Yeon Kwon, postdoctoral researcher Nokyoung Park, and Christopher Umbach, Cornell assistant professor of materials science and engineering.
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