DNA hydrogels are biocompatible drug supply programs for focused therapeutic interventions. Standard DNA hydrogels, shaped with many DNA nanostructure items, result in elevated preparation prices and design complexities. To deal with this, researchers from Japan constructed a Takumi-shaped DNA nanostructure with minimal DNA items and optimized its construction for improved in vivo retention skills and sustained drug launch. This research presents a promising DNA-based drug supply system, which may doubtlessly enhance affected person outcomes.
Hydrogels are polymeric supplies with three-dimensional community buildings containing giant quantities of water. They function sustained-release drug supply programs as they’ll encapsulate numerous bioactive substances, together with medication, antigens, and even cells. Hydrogels are higher drug supply alternate options than typical programs, as they’re extra biocompatible, biodegradable, and simply administered as an injectable scaffold.
DNA has gained vital consideration as a promising hydrogel materials because of its customizable physicochemical properties, resulting in the event of assorted DNA hydrogels. Nonetheless, present strategies like DNA ligase-linked hydrogels current many challenges, together with potential allergic reactions and complicated administration procedures that restrict scientific purposes.
Not too long ago, a polypod-like nanostructured nucleic acid, or polypodna, was constructed utilizing three or extra predesigned oligodeoxynucleotides (ODNs) with partially complementary sequences to deal with these challenges. These environment friendly DNA nanostructures are simply injectable and readily reform into hydrogels on the injection web site after being injected. Whereas this strategy creates self-gelatinizing nucleic acids that type hydrogels with out DNA ligase, it requires a number of ODNs, resulting in excessive preparation prices, design complexity, and an elevated chance of off-target results owing to the big variety of DNA bases concerned.
To deal with this, a Takumi-shaped DNA unit was shaped with solely two ODNs. Nonetheless, research investigating its optimization as a sustained-release drug provider or its retention potential are restricted.
Of their new research, made obtainable on-line on December 2, 2024, and to be printed on January 10, 2025, in Quantity 377 of the Journal of Managed Launch, Professor Makiya Nishikawa, together with Mr. Jian Jin, Assistant Professor Shoko Itakura, and Affiliate Professor Kosuke Kusamori, from the Tokyo College of Science, Japan, aimed to deal with these facets of Takumi-shaped DNA nanostructures.
Prof. Nishikawa defined the motivation behind the research, “Our aim was to miniaturize and optimize DNA nanostructures in order that steady DNA hydrogels could possibly be shaped with fewer nucleic acids.”
Every ODN within the Takumi-shaped DNA construction was constructed with an eight-18 nucleotide-long palindromic stem connected to 2 cohesive elements on both facet with a thymidine (T) spacer. The ODNs type a self-dimer through the palindromic sequence, and every ODN was named based on the variety of nucleotides within the stem and cohesive elements. As an example, 14s-(T-10c)2 refers to an ODN with a stem size of 14 nucleotides and a cohesive a part of 10 nucleotides situated at each ends of the stem.
To optimize the Takumi-shaped DNA as an injectable hydrogel unit with sustained retention, researchers systematically designed numerous ODN lengths and investigated the correlation between structural properties and hydrogel efficiency, with a particular concentrate on in vivo retention capabilities.
Their findings confirmed that the hydrogel properties, equivalent to melting temperatures and stability, rely upon the size of the stem and the cohesive elements. ODNs with stem lengths of 12 nucleotides or longer effectively shaped the hydrogel items, suggesting {that a} 12-nucleotide-long stem is sufficient for unit formation. Equally, cohesive elements demonstrated efficient hybridization and interactions at a size of 10 nucleotides.
The researchers additionally assessed the storage modulus of hydrogels, which helps perceive how the hydrogel modifications beneath totally different bodily situations, by various lengths of cohesive elements, demonstrating that 10-nucleotide-long GC-rich cohesive elements exhibit higher 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 type. In whole, simply 68 nucleotides had been wanted for DNA hydrogel formation — markedly lesser than the hexapodna-based DNA hydrogel composed of twelve totally different 40-base lengthy ODNs,”explains Prof. Nishikawa about how their research has achieved environment friendly hydrogel formation with minimal DNA items.
In vivo experiments with doxorubicin-intercalated DNA hydrogels of 12s-(T-10c)2-ODNs confirmed extended persistence of a minimum of 168 hours post-administration, contributing to pronounced anti-tumor results in mice, as a result of sustained launch of doxorubicin on the web site of injection. Moreover, Takumi-shaped DNA hydrogels might doubtlessly induce focused immune responses, making them efficient antigen-delivery programs. “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 programs for bioactive supplies,” concludes Prof. Nishikawa.
General, this research demonstrates how minimal DNA items can assemble to type biocompatible hydrogels with excessive retention instances and sustained drug launch capabilities, providing a promising biomedical innovation for focused therapies.
