Programmable DNA “Nanotransporters” Could Improve Cancer Treatment
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A new class of drug transporters have been created from DNA and are 20,000 times smaller than a human hair. This discovery, published in Nature Communications, could improve treatment for diseases like cancer.
Maintaining dosages remains a medical challenge
When using drugs to treat disease, maintaining the correct dosage throughout the course of treatment is key. If the drug concentration drops below the optimum therapeutic level, its efficiency will reduce and possibly lead to drug resistance. If the amount of the drug is too high, this can lead to unwanted side effects.
Sustaining the optimal concentration for a drug in the bloodstream remains difficult for clinicians. Drugs will often quickly degrade in the body, meaning patients must remember to take multiple doses of the drug each day.
The activity, metabolism and concentration of the drug over time can also fluctuate hugely between individuals. In fact, when it comes to treating cancer, only ~50% of patients will receive the optimum chemotherapy dosage during their treatment.
To try and tackle this problem, Dr. Alexis Vallée-Bélisle, associate professor in the department of chemistry at the University of Montreal, and his team explored how biological systems control and maintain the concentration of biomolecules. They began developing artificial transporters to deliver drugs, aiming to recreate the natural effect of maintaining their concentration during treatment.
“We have found that living organisms employ protein transporters that are programmed to maintain [the] precise concentration of key molecules such as thyroid hormones, and that the strength of the interaction between these transporters and their molecules dictates the precise concentration of the free molecule,” Vallée-Bélisle explained.
Accurate, sustained drug delivery
The researchers began with two DNA transporters – one for the antimalarial drug quinine, and another for the cancer chemotherapy drug doxorubicin. Experimental data showed that they could program these artificial transporters to deliver and subsequently maintain any desired drug concentration.
Arnaud Desrosiers, graduate student and lead author of the study, added, “Another impressive feature of these nanotransporters is that they can be directed to specific parts of the body where the drug is most needed – and that, in principle, should reduce most side effects.”
Testing the efficacy of the nanotransporters in mice, the researchers found that the doxorubicin formulation maintained doxorubicin levels in the blood for 18 times longer and reduced unwanted circulation of the drug into vital organs like the lungs, heart and pancreas.
“For now, we have demonstrated the working principle of these nanotransporters for two different drugs. But thanks to the high programmability of DNA and protein chemistries, one can now design these transporters to precisely deliver a wide range of therapeutic molecules,” explained Vallée-Bélisle.
Potential applications for blood cancer treatment
The research team is now planning to validate the effects of their discovery in the clinic, eager to test the doxorubicin transporters for the treatment of blood cancers.
“We envision that similar nanotransporters may also be developed to deliver drugs to other specific locations in the body and maximize the presence of the drug at tumor sites," summarized Vallée-Bélisle. "This would drastically improve the efficiency of drugs as well as decrease their side effects."
Reference: Desrosiers A, Derbali RM, Hassine S, et al. Programmable self-regulated molecular buffers for precise sustained drug delivery. Nat Comms. 2022;13(1):6504. doi: 10.1038/s41467-022-33491-7