Hydrogels that are crosslinked by DNA aptamers are triggered to release their cargo in the presence of specific target molecules
Making effective drugs is not easy. The first problem is finding a drug that works. Once you have one, the next challenge is to get the drug to where it is needed in the body. Hydrogels — water-insoluble networks of polymer chains — are potential candidates for carrying drugs, but the next and possibly most important step is to release the drug at the desired location.
Now, Weihong Tan and co-workers from the University of Florida, Gainesville have produced1 a hydrogel in which the crosslinking is controlled by DNA aptamers — short single-stranded pieces of DNA that bind to specific target molecules. The researchers made water-soluble polymers with two different short DNA strands attached to them. A linker molecule was also prepared that contains three DNA sequences: two complementary to those attached to the polymers, and the other an aptamer segment. When the polymer and linker combine, a gel is formed that can absorb drugs. The linker molecule can be engineered so that the aptamer overlaps with one of the complementary binding sequences. Thus the presence of a target molecule, which binds more strongly to the aptamer than to the pendant DNA strands, disrupts the crosslinking, causing the gel to dissolve and release its cargo.
Aptamers exist for a broad range of target molecules, including several cancer biomarkers. This presents the possibility that the same hydrogel system can be used to deliver a number of different drugs, simply by using linkers that incorporate different aptamers
Yang, H., Liu, H., Kang, H. & Tan, W. Engineering target-responsive hydrogels based on aptamer–target interactions. J. Am. Chem. Soc. 10.1021/ja801339w (2008).
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Davey, S. Right on target. Nature Chem (2008). https://doi.org/10.1038/nchem.7