Researchers from the University of Missouri (MU) have demonstrated a specialized technique that could one day be used to deliver drugs directly to cancer cells, while bypassing normal tissue. It is hoped methods such as this may help to address some of the drawbacks of current treatment options.
In recent years, targeted chemotherapies have become increasingly effective at treating cancer. However, many people experience side effects that can often have a harsher impact on the body than the disease itself. This is due to the fact that most therapeutic drugs do not differentiate between cancerous and healthy cells.
"Cancer chemotherapy drugs are famously harsh," Donald H. Burke-Agüero, from the Department of Molecular Microbiology & Immunology at MU and an author of a study published in the journal Nature Communications describing the technique, told Newsweek. "They put a strain on healthy tissues, such as hair follicles and the lining of the gut."
Furthermore, despite recent advances in the treatment of localized cancers—those that remain contained within their tissue-of-origin—most cancers still have a dismal prognosis once they have spread to distant sites, according to Scott Verbridge from Virginia Tech's School of Biomedical Engineering and Sciences, who was not involved in the study.
"Common treatment approaches simply do not deliver a therapeutic dose with enough selectivity or efficiency to cure these more systemic diseases, meaning that most of the treatment—which is often highly toxic to normal cells—is either delivered off-target, such as to bone marrow cells, or is otherwise cleared from the body instead of reaching the cancer," Verbridge told Newsweek.
In order to address this issue, cancer researchers have been increasingly looking towards nanotechnologies to deliver treatments precisely where they are needed.
"Targeted delivery is one of the grand challenges in cancer research," Burke-Agüero said. "The idea is to get chemotherapy drugs to go only to the tumor cells and to ignore the rest of the body's healthy tissues, so that tumors can be eliminated as completely as possible with as few side effects as possible."
So far, the benefits for patients have been relatively modest, according to Verbridge, because the development of truly selective therapies remains challenging. One approach that several research teams—including the one responsible for the latest study—are taking appears to be showing promise, however.
It involves harnessing the capabilities of "smart" nanoparticles called aptamers, which can be made to bind to specific targets—such as cancer cells—along with a therapeutic drug or "payload".
"Molecules have three-dimensional shapes," Burke-Agüero said. "Often, they also have little patches that act like molecular Velcro, making them sticky if they are matched up with another patch that is the opposite kind of Velcro. Sometimes two different molecules will have just the right shapes and have their Velcro patches arranged in just the right way that they fit snugly up against each other."
"Some aptamers grab onto proteins that are much more abundant on the surfaces of certain tumor cells than on healthy cells," he continued. "The aptamers then hitch a ride with those proteins as they get recycled back inside the cells. Next thing you know, the aptamer is inside the cell, taking with it anything that we have attached to [it]."
For the latest study, the team engineered nanoparticles, made up of aptamers and a fluorescent cargo, that both mimicked a cancer-targeting compound and provided a means of visualizing the particle's interactions in order to learn more about it.
They then placed these special nanoparticles among both target cancer cells and non-target cells. Promisingly, they found that only the malignant cancer cells were illuminated by the fluorescent payload, demonstrating that the aptamers had efficiently bonded with their desired target.
According to Burke-Agüero, the latest study is an important milestone in a long process: "The cargo that we have delivered is roughly 10 times larger, in a molecular sense, than what investigators typically work with," he said. "We have opened the door to exploring many other large cargos, each of which could tweak tumor cells in different ways. There is still lots of work to do, but each time we hit these new milestones, we can see that we are getting closer."
He noted that the field is becoming "very good" at using aptamers to target drug delivery. Nevertheless, he stresses that there is still room for improvement because not all methods that showed initial promise have withstood further scrutiny. Furthermore, while the use of aptamers is generally safe, some research has shown that there are exceptions, and their long-term effects on the body remain unknown.
Verbridge agrees that the new work shows promise as it gives more control over the complex processes involved in nanoparticle drug delivery when compared to traditional nanotherapies.
"However, as a caveat, it is important to keep in mind there are still major physical hurdles often preventing drugs or nanoparticles from even reaching malignant cells in the first place—such as the dense and poorly vascularized structure of tumors. These delivery challenges must also be tackled for there to be real breakthroughs for patients," Verbridge said.
"In other words researchers have learned a great deal about how to destroy malignant cells once a therapy reaches the cell and how to improve selectivity at this stage, however, much less attention has been given to the initial delivery."
The next step for the Missouri researchers is to prove definitively that these aptamers can be loaded with therapeutic substances that can specifically treat cancer cells, while leaving other tissues untouched.
Techniques such as the one in the latest study take inspiration from an old medical concept, known as the "magic bullet," which was first proposed in 1900 by German Nobel laureate Paul Ehrlich.
"Imagine a bullet that could look for its target, weave around obstacles, and only hit the thing that you wanted it to hit, with no damage to anything else along the way," Burke-Agüero said. "Now imagine a medicine that quietly eliminates all of a patient's tumor cells, no matter where they might be hiding, and that causes no damage at all to any healthy tissue. That is the literal idea of a 'magic bullet.'"
This article has been updated to include additional comments from Scott Verbridge.