Tokyo College of Science researchers have created optimized DNA hydrogels with attainable biomedical makes use of by using lowered Takumi-shaped DNA nanostructures. The examine was revealed within the Journal of Managed Launch.
Polymeric supplies that include loads of water and have three-dimensional community buildings are referred to as hydrogels. They perform as sustained-release drug supply methods by encapsulating varied bioactive substances, similar to medicine, antigens, and cells. In comparison with standard drug supply strategies, hydrogels supply superior biocompatibility, biodegradability, and ease of administration as an injectable scaffold.
Quite a few DNA hydrogels have been developed on account of DNA’s adaptable physicochemical traits, drawing a lot curiosity as a promising hydrogel materials. Present strategies, similar to DNA ligase-linked hydrogels, have a number of drawbacks, similar to the opportunity of allergic reactions and tough administration processes that limit their use in medical settings.
To beat these difficulties, a polypodna – a nanostructured nucleic acid that resembles a polypod – was lately created by combining three or extra premade oligodeoxynucleotides (ODNs) with partially complementary sequences. After being injected, these efficient DNA nanostructures simply reform into hydrogels on the injection website.
Though this technique produces self-gelatinizing nucleic acids that kind hydrogels with no need DNA ligase, it requires a number of ODNs, leading to excessive preparation prices, complicated design, and a better probability of off-target results as a result of giant variety of DNA bases concerned.
This was addressed utilizing simply two ODNs to create a Takumi-shaped DNA unit. Few research study its retention capability or optimization as a sustained-release drug provider.
These points of Takumi-shaped DNA nanostructures have been the main target of a latest examine by Professor Makiya Nishikawa, Mr. Jian Jin, Assistant Professor Shoko Itakura, and Affiliate Professor Kosuke Kusamori from Tokyo College of Science, Japan.
Our aim was to miniaturize and optimize DNA nanostructures in order that steady DNA hydrogels may very well be fashioned with fewer nucleic acids.
Makiya Nishikawa, Professor, Tokyo College of Science, Japan
Every ODN within the Takumi-shaped DNA construction was designed with an 8–18 nucleotide-long palindromic stem, flanked by two cohesive areas on both aspect, separated by a thymidine (T) spacer. The ODNs kind self-dimers by the palindromic sequence, and every ODN is called based mostly on the variety of nucleotides within the stem and cohesive areas. For instance, 14s-(T-10c)2 denotes an ODN with a 14-nucleotide stem and 10-nucleotide cohesive areas at each ends.
Researchers systematically designed totally different ODN lengths and examined the connection between structural traits and hydrogel efficiency, emphasizing in vivo retention capabilities to optimize the Takumi-shaped DNA as an injectable hydrogel unit with sustained retention.
The size of the stem and the cohesive parts have an effect on the hydrogel’s stability and melting temperatures. ODNs with stem lengths of 12 nucleotides or extra successfully created the hydrogel items, indicating {that a} stem that’s 12 nucleotides lengthy is enough for unit formation. At 10 nucleotide size, cohesive parts additionally confirmed good hybridization and interactions.
By various the size of cohesive elements, the researchers additionally evaluated the storage modulus of hydrogels, which aids in understanding how the hydrogel adjustments underneath varied bodily situations. They discovered that GC-rich cohesive elements which can be 10 nucleotides lengthy have superior thermal stability and storage modulus in comparison with different formations.
The size of the 12s-(T-10c)2-ODN, which confirmed the very best retention in mice, was 34 bases, requiring solely two ODNs to kind. In whole, simply 68 nucleotides have been wanted for DNA hydrogel formation―markedly lesser than the hexapodna-based DNA hydrogel composed of twelve totally different 40-base lengthy ODNs.
Makiya Nishikawa, Professor, Tokyo College of Science, Japan
As a result of sustained launch of doxorubicin on the injection website, in vivo experiments utilizing doxorubicin-intercalated DNA hydrogels of 12s-(T-10c)2-ODNs demonstrated extended persistence of no less than 168 hours post-administration, which contributed to pronounced anti-tumor results in mice. Moreover, Takumi-shaped DNA hydrogels might set off particular immune reactions, making them environment friendly antigen-delivery autos.
The optimized DNA hydrogel ready utilizing 12s-(T-10c)2 exhibited a extra sustained retention than the hexapodna-based DNA hydrogel after in vivo administration in mice. These outcomes spotlight the applicability of DNA hydrogels as supply methods for bioactive supplies.
Makiya Nishikawa, Professor, Tokyo College of Science, Japan
This examine reveals that biocompatible hydrogels with lengthy retention intervals and sustained drug launch capabilities could be created from minimal DNA items, offering a promising biomedical innovation for focused therapies.
Takumi-Formed DNS Items Type Hydrogels with Sustained Drug Launch
Video Credit score: Tokyo College of Science
Journal Reference:
Jin, J., et al. (2025) Biocompatible DNA hydrogel composed of minimized Takumi-shaped DNA nanostructure displays sustained retention after in vivo administration. Journal of Managed Launch. doi.org/10.1016/j.jconrel.2024.11.052
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