(Nogas1974, Wikimedia Commons)
30 Apr. 2019. Researchers in Finland developed tiny drug-delivery capsules made of folded pieces of DNA, with the capsules opening and closing in specified chemical environments. The team from University of Jyväskylä and Aalto University in Helsinki describe the technology in the 16 April issue of the journal ACS Nano (paid subscription required).
The team from the biomaterials lab of Aalto University polymer chemistry professor Mauri Kostiainen is seeking better methods for delivery of drug nanoparticles using the natural substance DNA as the delivery method. Nanoscale particle drug formulations are often considered desirable for targeted treatments and drugs released over an extended period of time. In a recent story, Science & Enterprise described experiments sponsored by drug maker AstraZeneca sent to the International Space Station testing effects of microgravity or weightlessness on drug nanoparticles.
For this task, the researchers faced a number of hurdles, including preparation of DNA strands into capsule-like packages, and a programmable triggering mechanism to open the package at the right time. Plus, the entire package must be small enough to interact with individual cells.
The team led by Veikko Linko, now an adjunct professor in biomaterials at Aalto, took advantage of characteristics in DNA that allow the nucleic acids in DNA to be synthesized and constructed for purposes other than describing genetic codes. Among these properties is DNA’s extremely small size, making it possible to put together strands of DNA into more complex structures, while still at nanoscale dimensions, where 1 nanometer equals 1 billionth of a meter.
Linko and colleagues constructed strands of DNA into capsule-like devices. The researchers folded complementary triple strands of DNA that bond together with similar hydrogen atoms. In addition, the strands could be folded in patterns based on origami, the Japanese art of paper folding. This design creates open spaces for drug molecule cargoes, while keeping the overall structure nanoscale in size.
The team then tackled programming the package to open at the right time to release its drug cargoes. The team chose complementary triple DNA strands for the package with chemistries that respond to specific pH levels, indicating levels of acids or bases in the solutions, opening and closing in the presence of specific concentrations.
“The triplex formation can happen only when the surrounding pH of the solution is right,” says doctoral candidate and first author Heini Ijäs, in a University of Jyväskylä statement. “We call these pH-responsive strands ‘pH latches’, because when the strands interact, they function similarly to their macroscopic counterparts and lock the capsule in a closed state.” Ijäs adds, “The opening of the capsule is actually very rapid and requires only a slight pH increase in the solution.”
The researchers tested DNA capsules in the lab with gold nanoparticles and enzymes, and at various pH levels. The team demonstrated the DNA capsules opening at high pH levels to fill the capsules with cargoes, then closing at low pH for delivery, and opening again at high pH levels to release the cargoes. The researchers also tested the capsules in magnesium and sodium solutions.
“The most intriguing thing about the DNA origami capsules,” notes Linko, “is that the threshold pH at which the opening and closing take place is fully adjustable by selecting the base sequences of the pH latches. We designed the threshold pH to be 7.2-7.3, close to the blood pH. In the future, this type of drug carrier could be optimized to selectively open inside specific cancer cells, which can maintain a higher pH than normal healthy ones.”
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