researchers from University of Montréal have designed and validated a new class of drug carriers made of DNA that are 20,000 times smaller than a human hair and could improve the way cancers and other diseases are treated. reported in the newspaper nature communicationsthese molecular carriers can be chemically programmed to deliver an optimal concentration of drugs, making them more efficient than current methods.
Maintaining an optimal concentration of drugs in the blood remains a major challenge in modern medicine. Since most drugs degrade rapidly, patients are forced to (and often forget to) take multiple doses at regular intervals, and because each patient has a different pharmacokinetic profile, the concentration of drugs in the blood varies. significantly. Noting that only about 50% of cancer patients get an optimal dose of the drug during a given chemotherapy, Associate Professor Alexis Vallée-Bélisle began exploring how biological systems control and maintain the concentration of biomolecules.
“We discovered 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 Belisle said. This led him and his team to begin developing artificial drug carriers that mimic the natural effect of maintaining a precise concentration of a drug during treatment.
PhD student Arnaud Desrosiers, the study’s first author, initially identified and developed two DNA carriers: one for quinine, an antimalarial, and the other for doxorubicin, a drug commonly used to treat breast cancer and leukemia. . He then showed that these artificial transporters could be easily programmed to deliver and hold any specific concentration of drug.
“More interestingly, we also found that these nanocarriers could also be used as a drug reservoir to prolong the effect of the drug and minimize its dose during treatment,” said Desrosiers.
“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.”
Using the nanocarrier developed for doxorubicin, the researchers and their collaborators demonstrated that a specific drug carrier formulation allows doxorubicin to remain in the blood and dramatically reduces its diffusion to key organs such as the heart, lungs, and pancreas. In mice treated with this formulation, doxorubicin remained in the blood 18 times longer and cardiotoxicity was also reduced, keeping the mice healthier, as evidenced by their normal weight gain.
“Another great property of our nanocarriers is their great versatility,” said Vallée-Bélisle.
“So far, we have demonstrated the working principle of these nanocarriers for two different drugs. But thanks to the highly programmable power of DNA and protein chemistry, these transporters can now be designed to precisely deliver a wide range of therapeutic molecules.
“In addition, these transporters could also be combined with human-designed liposomal transporters that are now used to deliver drugs at different rates.”
The researchers are now eager to validate the clinical efficacy of their discovery. Since their doxorubicin nanocarrier is programmed to optimally keep the drug in the bloodstream, they believe it could be ideal for treating 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,” Vallée-Bélisle said.
“This would drastically improve the efficiency of the drugs and decrease their side effects.”