DNA, which is often called the blueprint of life, is composed of four chemical bases: adenine (A), guanine (G), cytosine (C) and thymine (T), which are paired together in a complementary fashion (A to T and C to G) and ordered in a specific sequence. DNA encodes information (important for constructing the protein machinery that makes a living cell work) in its base sequences and this information makes it sensitive to external stimuli.

Researchers have exploited this fact to make stimuli-responsive DNA-based materials and carriers. Some examples include stimuli-responsive hydrogels, origami nanostructures and DNA-functionalized nanocarriers. Triggers such as such as pH, enzymes, light or heat can be used to switch the function of the DNA-based nanostructures, which might be used in applications like controlled drug delivery, actuators and nanoreactors.

DNA microcapsules unlock at acidic pH

Now, a team led by Itamar Willner has succeeded in fabricating QD-loaded pH-responsive microcapsules made from DNA that unlock at acidic pH and so release their load. Unlocking involves the dissociation of T-A.T “triplex” structures.

The researchers prepared their microcapsules by depositing nucleic acid layers on CaCO3 nanoparticles coated with the QD loads (made from semiconducting cadmium selenide/zinc sulphide). “The layers of the nucleic acids are crosslinked by pH-sensitive “bridges” that allow stable nuclei shells to form on the microparticle cores,” explains Willner. “We then dissolve the CaCO3 core (using EDTA, or ethylenediaminetetraacetic acid) to produce the capsules loaded with the QDs.”

Chemotherapeutic drug carriers

Since the microcapsules are made of DNA, we expect them to have a minimal immunogenic effect, he tells nanotechweb.org. And since the QDs luminesce brightly, they could make useful imaging agents.

According to the team, the stimuli-responsive microcapsules could find use as chemotherapeutic drug carriers. “We know that microcapsules can penetrate cells and cancer cells,” adds Willner. “Since cancer cells are acidic, we expect the microcapsules to specifically unlock here, resulting in the selective unloading of anti-cancer drugs contained within them.” The capsules should not be toxic to surrounding normal cells since they preferentially enter cancerous ones.

The team, reporting its work in ACS Nano DOI: 10.1021/acsnano.6b04056, says that it is now busy designing nucleic acid microcapsules that respond to biomarkers of different diseases. “In these systems, ligand-aptamer complexes should dissociate the nanostructures,” says Willner.