Nanotechnology: Molecules that carry anti-cancer drugs

The advance, which also includes malaria treatment, would prevent dosing problems and hospital readmissions

In the 19th century, the French chemist Henri-Louis Le Châtelier established a principle that today bears his name and basically states that “if a system in equilibrium is disturbed, the system evolves to counteract said disturbance and seeks a new equilibrium state.” ». This is a characteristic of biological systems, which are designed to respond (ie seek balance) in their environment. The problem is that artificial systems do not.

This ability is key because biological systems are designed to respond to their environment. As such, natural molecular regulators ensure the precise and quantitative delivery of specific molecules with self-regulating mechanisms based on Le Chatelier’s principle.

One of the key factors in achieving successful treatment of, for example, a disease is to provide and maintain a therapeutic dose of the drug throughout the treatment. Thus, an exposure below or above the adequate dose reduces the effectiveness of the treatment; the first generates drug resistance and the second increases side effects. Therefore, maintaining an optimal therapeutic concentration at the target site remains a major challenge in medicine. Most drugs undergo rapid degradation, forcing patients to take multiple doses at regular intervals (which is not always possible) during the course of their treatment. And because each patient has a different profile, the concentration of drugs in their blood varies significantly.

Noting that only about half of cancer patients get an optimal dose of drugs during their treatment, a team of Université de Montréal scientists, led by Alexis Vallée-Bélisle, an expert in bioinspired nanotechnologies, began to explore how Biological systems control and maintain the concentration of biomolecules. That is, how these natural systems seek the balance referred to in Le Châtelier’s principle.Initially, Vallée-Bélisle’s team discovered two regulators with great potential, one for doxorubicin (a drug used in chemotherapy) and another linked to the antimalarial agent quinine. In a study published in ‘Nature’, the authors demonstrated that the two regulators can be programmed to maintain any specific drug concentration while allowing optimization of chemical stability and biodistribution of the drug. As if this were not enough, these programmable regulators can be built from any polymer, something that should improve the therapeutic outcome of the patient, the activity of the drug and minimize adverse effects. These drug nanocarriers are made of DNA and are 20,000 times smaller than a human hair.

“We found that living organisms use protein transporters that are programmed to maintain the precise concentration of key molecules such as thyroid hormones, and that the interaction between these transporters and their molecules dictates the precise concentration,” explains Vallée-Bélisle. More interestingly, we also found that these nanocarriers could also be used as a drug reservoir to prolong drug effect and minimize drug dose during treatment.”

Using the newly developed drug transporter for doxorubicin, the team demonstrated that a specific drug transporter formulation allows this drug to remain in the blood, dramatically reducing its diffusion to key organs such as the heart, lungs, and pancreas. This further contributes to avoiding unwanted or directly dangerous side effects. In mice treated with this formulation, doxorubicin remained 18 times longer in the blood while reducing cardiotoxicity, keeping the mice healthier.

“Another impressive feature of these nanocarriers – adds Vallée-Bélisle – is that they can be targeted to specific parts of the body, where the drug is most needed, and that, in principle, should reduce most side effects. Another great property of our nanocarriers is their great versatility to potentially work with other drugs. So far, we have shown that they work for two specific drugs, but thanks to the highly programmable chemistry of DNA and protein, these transporters can now be engineered to precisely deliver a wide range of therapeutic molecules.In addition, these transporters could also be combined with liposomal transporters that are now being used to deliver drugs at various rates.” These small molecules designed by Vallée-Bélisle’s team would not only make it possible to control doses, reduce harmful effects and the effect on other organs, they could also be programmed with specific targets and “release” their cargo at different stages. The next step is to explore its use for new treatments or different types of tumors. Given that the doxorubicin nanocarrier is programmed to optimally maintain the drug in the bloodstream, it could be useful for treating blood cancer. And that would only be the first step. “We believe – concludes Vallée-Bélisle – that similar nanocarriers can also be developed to deliver drugs to other specific sites in the body and maximize their presence in tumor areas.