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A new drug transporter made of DNA has been designed and validated, 20,000 times smaller than human hair, and could improve treatments for
cancer and other diseases.
These molecular transporters can be chemically programmed to deliver optimal concentrations of drugs, making them more efficient
than current methods.
A team of Canadian researchers from the University of Montreal (UdeM) reports these details in a new study that will be published today (November 2) in the journal Nature Communications
.
Providing and maintaining a therapeutic dose throughout treatment is one of
the key ways to successfully treat a disease.
Excessive exposure to treatment can increase side effects
.
On the other hand, suboptimal treatment exposure reduces efficiency and often leads to drug resistance
.
A major challenge in modern medicine is to maintain an optimal concentration of
drugs in the blood.
Since most drugs degrade quickly, patients are forced to take multiple doses
on a regular basis.
Many patients often forget to take their medication on time, resulting in a lower than optimal dose
.
Because the pharmacokinetic profile of each patient is different, the concentration of the drug in their blood varies greatly
.
Alexis Vallée-Bélisle, an associate professor of chemistry at UdeM and an expert in bionanotechnology, observed that only about 50 percent of cancer patients receive the optimal dose of drugs during a particular chemotherapy process and set out to explore how biological systems control and maintain concentrations
of biomolecules.
"We have found that living organisms use protein transporters to maintain precise concentrations of key molecules, such as thyroid hormones, and the strength of the interactions between these transporters and their molecules determines the precise concentrations
of free molecules," he said.
This simple idea prompted Valléé-Belisle and his research team to set out to develop artificial drug transporters that mimic the natural effects
of maintaining precise concentrations of drugs during treatment.
Arnaud Desrosiers, a doctoral student at UdeM and first author of the study, initially identified and developed two DNA transporters: one for the antimalarial drug quinine and another for the commonly used drug doxorubicin
, which is used to treat breast cancer and leukemia.
He then demonstrated that these artificial transporters could be easily programmed to deliver and maintain any specific concentration of the drug
.
Desrosiers said: "More interestingly, we also found that these nanotransporters can also be used as drug repositories to prolong the effects of drugs and reduce drug doses
during treatment.
Another impressive feature of these nanotransporters is that they can be directed to specific parts of the body that need drugs the most — which should, in principle, reduce most side effects
.
”
To demonstrate the effectiveness of these nanotransporters, the researchers teamed
up with Jeanne Leblond-Chain, pharmacist at Université de Bordeaux in France.
Using a novel drug transporter developed for doxorubicin, the team demonstrated that a specific drug transporter formulation keeps doxorubicin in the blood and drastically reduces its spread
to key organs such as the heart, lungs, and pancreas.
In mice treated with this formula, doxorubicin maintained 18-fold longer in the blood, and cardiotoxicity was reduced, making the mice healthier, as evidenced
by their normal weight gain.
"Another great property of our nanotransporters is their high versatility," says
Vallée-Bélisle.
"Currently, we have demonstrated how these nanotransporters work
against two different drugs.
But thanks to the highly programmable nature of DNA and protein chemistry, these transporters can now be engineered to deliver a wide range of therapeutic molecules
with precision.
In addition, these transporters can bind to human-designed liposomal transporters, which are currently being used to deliver drugs
at different speeds.
”
The researchers are now eager to validate the clinical effects
they found.
They believe that their doxorubicin nanotransporter can optimally keep the drug circulating in the bloodstream, and it can be used to treat blood cancers
.
Vallée-Bélisle said: "We envision that similar nanotransporters could also be developed to deliver drugs to other specific locations in the body and maximize the presence of drugs at tumor sites
.
This will greatly increase the efficiency of the drugs and reduce their side effects
.
”
Reference: "Programmable self-regulated molecular buffers for precise sustained drug delivery" 2 November 2022
