Nanotransporters made from DNA can help fight cancer and other diseases
Nanobots that can deliver a payload of drug treatments and other agents have been studied as cancer treatments for years. In one of the latest advances, researchers from Université de Montréal (UdeM) developed a new class of drug transporters made from DNA that are 20,000 times smaller than the width of a human hair, according to a press release published by the institution.
When delivered in mice, the nanotransporters were able to maintain the drug in the blood for 18 times as long as the conventional delivery system, proving their efficiency in treating cancer and other diseases.
Delivering drugs to their target
Cancer drugs usually take a scattergun approach. Chemotherapies inevitably hit healthy bystander cells while blasting tumors, resulting in a myriad of side effects. Also, patients are given repeated drug doses at regular intervals as most drugs are degraded once in the bloodstream.
Nanobots could circumvent this issue by protecting the drug until it's delivered to the intended target. These miniature machines could also navigate directly to a tumor and smartly deploy a therapeutic payload right where it's needed without collateral damage.
Keeping this in mind, a team led by UdeM Prof Alexis Vallée-Bélisle came up with a potential solution using bio-inspired nanotechnology. They developed DNA-based drug transporters that mimic the ability of protein transporters found in living organisms to maintain the precise concentration of specific molecules in the body.
"We 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," said UdeM Chemistry associate professor Alexis Vallée-Bélisle.
The team developed two DNA-based transporters: one for quinine, an antimalarial, and the other for doxorubicin, a commonly used drug for treating breast cancer and leukemia.
They demonstrated that these artificial transporters could be readily programmed to deliver and maintain any specific drug concentration in the body. Another exciting feature of these nanotransporters is that they can be used as drug reservoirs to minimize the dosage and can be directed to specific body parts, effectively reducing the drug side effects.
Reduced cardiotoxicity in nanotreated mice
To demonstrate their effectiveness, researchers performed in-vivo studies in mice. They showed that the new drug transporter developed for doxorubicin could maintain the drug in the blood for 18 times as long as conventional delivery methods. It also prevented the drug from leaching out into other organs, such as the heart and lungs, and kept the mice more healthy, as evidenced by their normal weight gain.
"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 therapeutic molecules," said Prof Alexis Vallée-Bélisle.
Nanotransporters to treat blood cancers?
Looking forward, the team intends to perform clinical studies to validate their discovery. Since the doxorubicin nanotransporter can maintain the drug in blood circulation, it could be ideal for treating blood cancers.
"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. This would drastically improve the efficiency of drugs as well as decrease their side effects," said Prof Alexis Vallée-Bélisle.
The results of the new study were published in Nature Communications.
Unlike artificial nanosystems, biological systems are ideally engineered to respond to their environment. As such, natural molecular buffers ensure precise and quantitative delivery of specific molecules through self-regulated mechanisms based on Le Chatelier's principle. Here, we apply this principle to design self-regulated nucleic acid molecular buffers for the chemotherapeutic drug doxorubicin and the antimalarial agent quinine. We show that these aptamer-based buffers can be programmed to maintain any specific desired concentration of free drug both in vitro and in vivo and enable the optimization of the chemical stability, partition coefficient, pharmacokinetics and biodistribution of the drug. These programmable buffers can be built from any polymer and should improve patient therapeutic outcome by enhancing drug activity and minimizing adverse effects and dosage frequency.
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