A new class of drug carriers have been created from DNA and are 20,000 times smaller than a human hair. This discovery, published in nature communications, could improve the treatment of diseases such as cancer.
Maintaining doses remains a medical challenge
When medicines are used to treat diseases, it is essential to maintain the correct dose throughout the course of treatment. If the concentration of the drug falls below the optimal therapeutic level, its efficacy will be reduced and possibly lead to drug resistance. If the amount of the drug is too high, this can lead to unwanted side effects.
Maintaining the optimal concentration of a drug in the bloodstream remains difficult for clinicians. Medications often break down quickly in the body, which means patients must remember to take multiple doses of the medication each day.
Drug activity, metabolism, and concentration over time can also fluctuate greatly between individuals. In fact, when it comes to treating cancer, only ~50% of patients will receive the optimal dose of chemotherapy during their treatment.
To try to address this problem, Dr. Alexis Vallee-Belisle, an 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 to develop artificial transporters to deliver drugs, with the aim of recreating 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 and sustained drug delivery
The researchers started with two DNA carriers: one for the antimalarial drug quinine and one for the cancer chemotherapy drug doxorubicin. Experimental data showed that these artificial transporters could be programmed to deliver and subsequently maintain any desired drug concentration.
Arnaud Desrosiersgraduate student and lead author of the study, additional“Another impressive feature of these nanocarriers is that they can target specific parts of the body where the drug is most needed, and that should, in principle, reduce most side effects.”
Testing the effectiveness of the nanocarriers in mice, the researchers found that the doxorubicin formulation maintained blood levels of doxorubicin for 18 times longer and reduced unwanted circulation of the drug in vital organs such as the lungs, heart and pancreas. .
“So far, we have demonstrated the working principle of these nanocarriers for two different drugs. But thanks to the highly programmable ability of DNA and protein chemistry, these transporters can now be designed to precisely deliver a wide range of therapeutic molecules.” explained Vallée-Bélisle.
Possible applications for the treatment of blood cancer
The research team now plans to validate the effects of their discovery in the clinic, eager to test doxorubicin transporters for the treatment of blood cancers.
“We envision that similar nanocarriers can also be developed to deliver drugs to other specific locations in the body and maximize drug presence at tumor sites.” summarized Vallée-Bélisle. “This would dramatically improve the efficiency of the drugs and decrease their side effects.”
Reference: Desrosiers A, Derbali RM, Hassine S, et al. Programmable self-regulating molecular buffers for precise and sustained drug delivery. National Communications. 2022;13(1):6504. do: 10.1038/s41467-022-33491-7