HomeScience and ResearchScientific ResearchA Medical Challenge In Cancer Treatment Seems Solved

A Medical Challenge In Cancer Treatment Seems Solved

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One of the most important aspects of properly treating sickness or cancer is to give and maintain a therapeutic drug dosage during treatment. Overexposure raises 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 receive the recommended drug dosage during some chemotherapy and began to investigate how biological systems regulate and maintain the concentration of biomolecules.

And they “have found that living organisms employ protein transporters that are programmed to maintain 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.”

This straightforward notion prompted Valléé-Belisle and his research group to begin creating synthetic drug transporters that mimic the natural effect of preserving a precise concentration of a drug during treatment. Valléé-Belisle holds a Canada Research Chair in bioengineering and bionanotechnology.

The first author of the study, UdeM PhD student Arnaud Desrosiers, found and designed two DNA transporters made of DNA that are 20,000 times smaller than a human hair: one for quinine, which is used to treat malaria, and the other for doxorubicin, which is often used to treat breast cancer and leukemia.

Then he showed how these synthetic transporters could be easily configured to deliver and maintain any certain drug concentration.

“More interestingly, we also found that these nanotransporters could also be employed as a drug reservoir to prolong the effect of the drug and minimize its dosage during treatment,” Desrosiers said.

“Another impressive feature of these nanotransporters,” he added, “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.”

Researchers worked with Jeanne Leblond-Chain, a pharmacist at Université de Bordeaux in France, Luc DesGroseillers, a biochemist at UdeM, Jérémie Berdugo, a pathologist at UdeM, Céline Fiset, a pharmacist at the Montreal Heart Institute, and Vincent De Guire, a clinical biochemist at the UdeM-affiliated Maisonneuve-Rosemont Hospital, to show how well these nanotransporters work

Using the new drug transporter made for doxorubicin, the team showed that a specific drug-transporter formulation keeps doxorubicin in the blood and stops it from spreading to 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.

“Another great property of our nanotransporters is their high versatility,” added Vallée-Bélisle.

“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 threrapeutic molecules.”

Additionally, he continued, “additionally, these transporters could also be combined with human-designed liposomic transporters that are now being employed to deliver drugs at various rates.”

The researchers are now eager to prove that their discovery works in the real world. They believe their doxorubicin nanotransporter may be useful in the treatment of blood cancers since it is designed to keep the medicine in blood circulation as effectively as possible.

“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,” added Vallée-Bélisle. “This would drastically improve the efficiency of drugs as well as decrease their side effects.”

The findings of the study were published today in the journal Nature Communications

Source: 10.1038/s41467-022-33491-7

Image Credit: Monney Medical Media / Caitlin Monney

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