Researchers from the Université de Montréal in Canada have created and verified a new class of DNA-based drug transporters that are 20,000 times smaller than a human hair and may enhance the treatment of cancer and other disorders.
According to a recent study published in Nature Communications, these molecular transporters can be chemically engineered to deliver medications in the best concentration possible, outperforming existing techniques.
A medical challenge: ensuring optimal dose at all times
Providing and maintaining a therapeutic drug dosage during treatment is one of the most important factors in the successful treatment of disease. Overexposure causes side effects, whereas sub-optimal therapeutic exposure decreases effectiveness and often results in drug resistance.
In contemporary medicine, maintaining an ideal medication concentration in the blood is still a significant difficulty. Patients are required to take many dosages at regular intervals (and frequently forget to do so) because the majority of medications degrade quickly. Additionally, each patient has a unique pharmacokinetic profile, which causes significant variation in the medication concentration in the blood.
Alexis Vallée-Bélisle, an associate professor of chemistry and a specialist in bio-inspired nanotechnologies, noticed that only about 50% of cancer patients received the recommended drug dosage during some chemotherapy and began to investigate how biological systems regulate and maintain the concentration of biomolecules.
According to his research, “we have discovered that living organisms use protein transporters that are programmed to maintain precise concentrations of important molecules, such as thyroid hormones, and that the strength of the interaction between these transporters and their molecules determines the precise concentration of the free molecule.”
This straightforward notion inspired Valléé-Belisle and his research group to start creating synthetic drug transporters that mimic the natural effect of maintaining a precise concentration of a drug during treatment. Valléé-Belisle holds a Canada Research Chair in bioengineering and bionanotechnology.
Arnaud Desrosiers, a PhD student at UdeM, is the study’s primary author. He discovered and created two DNA transporters: one for the antimalarial quinine and the other for the chemical doxorubicin, which is frequently used to treat leukemia and breast cancer.
Then he showed how these synthetic transporters could be easily configured to deliver and maintain any certain drug concentration.
More intriguingly, Desrosiers added, “we also discovered that these nanotransporters could be used as drug reservoirs to extend the duration of the impact of the drug and lower its dosage during therapy.”
He continued, “Another interesting aspect of these nanotransporters is that they can be guided to specific body areas where the medicine is most needed—aand that, in theory, should decrease most side effects.”
decreased cardiotoxicity in nanotreated mice
The researchers collaborated with Jeanne Leblond-Chain, a pharmacist at the Université de Bordeaux in France, Luc DesGroseillers, a biochemist at the University of Montreal, Jérémie Berdugo, a pathologist at the University of Montreal, Céline Fiset, a pharmacist at the Montreal Heart Institute, and Vincent De Guire, a clinical biochemist at the Maisonneuve-Rosemont Hospital, which is affiliated with UdeM, to show the
The team found that a particular drug-transporter formulation enables doxorubicin to be kept in the circulation and significantly inhibits its diffusion towards important organs like the heart, lungs, and pancreas.
This formulation kept doxorubicin in the blood of mice 18 times longer than usual and minimized cardiotoxicity, keeping the mice healthier as seen by their normal weight gain.
The tremendous adaptability of our nanotransporters is another fantastic quality, according to Vallée-Bélisle.
“For the time being, we have shown how these nanotransporters function with two different medicines. But now that DNA and protein chemistries are highly programmable, it is possible to construct these transporters to precisely distribute a variety of therapeutic compounds.”
Additionally, he continued, “These transporters might be paired with human-designed liposomic transporters, which are now being used to deliver medications at varied speeds.”
A medical investigation into blood cancers?
The scientists are now eager to confirm if their discovery works clinically. They believe their doxorubicin nanotransporter may be useful in the treatment of blood malignancies since it is designed to keep the medicine in blood circulation as effectively as possible.
According to Vallée-Bélisle, similar nanotransporters could be created to deliver medications to other specified parts of the body and increase their concentration at tumor sites. This would significantly reduce negative effects while also increasing medicinal efficacy.
