Researchers have engineered a new method of drug delivery in which folded pyramids of DNA are capable of dispatching powerful antibiotics and/or chemotherapy drugs directly into pathogenic bacteria cells. Given the urgent public health concerns about the growing number and variety of antibiotic resistant bacteria, such developments have the potential to help doctors more efficiently utilize the antibiotics currently at their disposal.
A “drug delivery system” refers to the particular manner in which a drug is introduced into a person’s body. Oral ingestion, inhalation, intravenous injection, and absorption through the skin are all examples of different types of drug delivery systems.
The particular method used to introduce a drug into a patient can often be tailored to control the rate at which the medicine is released and even where within the body it is released. Some drugs must be delivered “systemically” which means that they will affect the whole body. In such cases side effects are a particularly poignant concern as different parts of the body may respond differently to the treatment. In addition, the different kind of drug delivery system that is used can also affect the degree to which a treatment’s effects are maximized. Drugs that can be delivered locally rather than systemically not only reduce the risk of undesired side effects and toxicity, but also can help augment the chances that the treatment will succeed.
Keeping these benefits in mind, many research teams have dedicated themselves to the task of creating new locally administered drug delivery systems that offer the doctor more control over the treatment of their patients. To this end, a variety of different approaches have been explored, ranging from chemically engineered nanosponge delivery vehicles to collagen-based therapies that can be topically applied. But in many of these new carrier systems concerns abound about unwanted complications such as toxicity and carcinogenicity.
In a novel approach to the problem, researchers from Singapore have created an experimental drug-delivery system that employs the technology of folded DNA. Since the 1980s scientists have experimented with folding and shaping DNA into what has become colloquially referred to as “DNA origami.” At first this science/art was limited to the creation of simple structures such as tubes or sheets. However as technological capabilities have caught up to the researcher’s imaginations, scientists have been able to bend DNA into the shapes of smiley faces, functional molecular rulers, and latched boxes that then be opened with a separate DNA “key.”
With respects to creating the new drug delivery system, the researchers modified self-assembling DNA nanopyramids. Into the struts of this structure the scientists incorporated molecules of the drug actinomycin D (also known as AMD, Dactinomycin or Cosmegen). In addition, the researchers also affixed molecules of red-emissive glutathione-protected gold nanoclusters (GSH-Au NCs) which acted as trackers so that the scientists would know if and when the DNA pyramids entered into a bacterial cell.
In testing, the new DNA-AMD-tracker complexes were demonstrated to be quite effective against common strains of model bacteria such as Escherichia coli (aka “E. coli”) and Staphylococcus aureus. The combination treatment killed 65 percent of S. aureus—up from the 42 percent of the bacteria that died when AMD alone was applied. Likewise, the DNA-pyramid delivery system upped the lethality to E. coli from 14 percent to 48 percent.
In their paper published in ACS Applied Materials and Interface, the researchers described their work as “a basic platform for future improvements to detect infectious bacteria and treatment.” Future experimentation will hopefully reveal more about the effectiveness of this treatment, potential side effects, and toxicity. Though exploring this drug delivery system (or any other) will required a considerable investment of time and resources, novel approaches such as these will be key to the future of pharmaceutical research.
By Sarah Takushi
ACS Applied Materials and Interface
ACS News Science Weekly
Children’s Hospitals and Clinics of Minnesota
Current Medicinal Chemistry
World Wide Wounds