They’re microscopic, autonomous, and on a mission.
They are nanorobots programmed to seek and destroy tumors. And it’s not science fiction.
Scientists from Arizona State University, with researchers from the National Center for Nanoscience and Technology of the Chinese Academy of Sciences, have successfully programmed nanorobots to shrink tumors in mice.
It’s a major breakthrough in the field of nanomedicine for cancer.
Radiation and chemotherapy are common cancer treatments. They’re often quite effective in destroying cancer cells.
They can also cause serious damage to healthy tissue, with long-term consequences.
In this first-of-a-kind study in mammals, the researchers developed a way to attack cancerous tumors while preserving healthy tissue.
They programmed the nanorobots to find these tumors and cut off their blood supply.
Details of the study are published in Nature Biotechnology.
How nanorobots kill tumors
The researchers in this study used a mouse tumor model.
Human breast, melanoma, ovarian, and lung cancer cells were injected into mice to spur tumor growth.
Once the tumors grew, the nanorobots were injected into the mice.
The nanorobots were made from flat, rectangular DNA origami sheets 90 nanometers by 60 nanometers. They were outfitted with an enzyme called thrombin, which helps blood to clot.
The nanorobots traveled the bloodstream carrying a DNA aptamer. The DNA aptamers targeted a protein called nucleolin, high amounts of which are found only on the surface of tumor endothelial cells. This particular protein is not found on the surface of healthy cells.
After locating and binding to the tumor blood vessel surface, the nanorobots opened up and delivered the thrombin. This caused clotting in blood vessels that feed tumor growth, cutting off the blood supply and killing tumor tissue.
And it happened quickly.
Within a few hours of injection, the nanorobots had gathered in large numbers around tumors.
Within 24 hours, tumor blood supply was blocked and tissue damage had begun.
Healthy tissues were not affected.
There was no evidence of the nanorobots entering the brain, where they might cause serious side effects.
The researchers found the nanorobots to be safe and effective in shrinking tumors in both mice and Bama miniature pigs.
Most nanorobots were cleared from the body after 24 hours.
In the mouse model, median survival time doubled from 20 days to 45 days.
Dr. Santosh Kesari is a neurologist and neuro-oncologist and chair of the Department of Translational Neurosciences and Neurotherapeutics at the John Wayne Cancer Institute at Providence Saint John’s Health Center in California.
Kesari told Healthline that there are currently many drugs that go to the tumor within a few hours of administration, but tumor shrinkage can take a long time.
“This approach seems a little faster than normal because it’s not attacking the tumor cell — it’s attacking by cutting off the blood supply and causing acute symptoms, similar to a stroke, in the tumor. Blood clots happen fast. We do see a similar effect with other angiogenesis drugs, like Avastin, that have a pretty quick effect relative to chemo for solid tumors,” he said.
Nanorobots can’t go it alone
In addition to targeting tumors, cancer treatment often requires a systemic approach.
That’s because cancer cells can break off the primary tumor and travel through the blood and lymphatic systems.
According to Kesari, the treatment used in the study will only work in the context of tumor blood vessels.
“It won’t target single cells. A group of tumor cells come together and start making new blood vessels. Only then can the drug be delivered to those sites,” he said.
In the study, the nanorobots did help prevent metastasis in the mice.
In an interview with Healthline, Dr. Jack Jacoub, medical oncologist and medical director of MemorialCare Cancer Institute at Orange Coast Medical Center in California, also helped put this research in perspective.
“This mechanism of action targets blood vessel formation. So, highly vascular tumors will be sensitive to this treatment. There are other agents we use now in multiple cancers to target blood vessel formation,” he said.
Cutting off blood supply may have some effect on circulating tumor cells that are spreading in the body, said Jacoub.
But it may not be enough.
“Cancer cells set up a location to grow, but they need nutrients to allow them to join with other cancer cells to create a tumor. In theory, it would affect them [circulating tumor cells], but it’s unlikely to be clinically meaningful. They might have already escaped the impact of this application. But it’s still early in animal models,” he said.
Jacoub said patients would likely still need additional drug therapy.
“This application combined with drug therapy would be a fairly realistic strategy for treatment. Chemotherapy, targeted drugs, biologic drugs. We’re moving away from traditional types of chemotherapy. There are a lot better therapies we include in the chemotherapy umbrella and it’s becoming a lot more refined,” he continued.
Jacoub suggested this application might help some patients avoid surgery.
“Or you might need it to reduce the size of a tumor before surgery. Limiting the blood supply of tumors will cause them to necrose or die without an adequate nutrient and blood supply,” he said.
The treatment used in the study slowed tumor growth and improved survival.
But Kesari notes that the mice are still dying of tumor burden.
“It seems safe because it doesn’t cause the normal toxicity of chemotherapy and radiation. So, I can imagine the next step will be to see how it will work in combination with chemotherapy and radiation. It’s potentially synergistic. Or it could be antagonistic. You need blood vessels to deliver drugs, so if you cut off the blood vessels, you can’t deliver more drugs,” said Kesari.
“This problem may be fixed with timing. For chemotherapy, it’s an issue. So, you would have to plan it that you give chemotherapy first, then this drug,” he explained.
Kesari said these are issues that could be figured out at the next level of analysis.
Jacoub observed some other potential issues.
For one thing, it’s an expensive proposition.
“It will require enormous resources to bring this technology to patients. They’ve got to find a pharmaceutical partner or a very deep-pocketed venture capital group,” he said.
There’s also a big difference between animal trials and human trials.
“What happens in animals and humans isn’t always identical when it comes to toxicity, efficacy, and tolerability. You’ve seen some benefit, but how much does it impact patient survival or curability? There are natural hurdles you have to go through for the development of technology like this, which are appropriate for the safety of patients,” said Jacoub.
The future of nanorobots
Until human clinical trials can be conducted, many questions will remain.
In addition to delivery, Jacoub believes the payload concept is also important.
“That is really what is working and it’s the nanorobots that deliver it. They’re trying to get this payload delivered. We have biologic agents that engage only with cancer cells because something on the surface (of the cell) allows it to be recognized as a cancer cell, and then release a payload. In this case, the researchers chose a payload that affects blood vessel formation. There’s a conceivable scenario of using multiple agents affecting different functions in cancer cells,” he said.
Jacoub explained that there are other nanoparticle-based therapies in late-stage clinical trials.
“Of course, the holy grail is not having it affect healthy cells. This is a very important field in oncology when it comes to chemotherapy. Over the next few years, you’ll see a movement away from the term [chemotherapy] even. It has a lot of connotations for both physicians and patients. We’re entering a totally different era,” he said.
As important as this latest research is, Jacoub cautions that it’s still early in development.
“Readers should understand that this is perhaps the next frontier parallel to immunotherapy and other therapies in cancer care. There’s a whole host of companies with similar technologies. Some will ultimately reach patients,” he continued.
“Progressing from phase 1 trials through phase two and phase three takes years,” said Jacoub. “That’s a big leap. We’ll have to see how it goes.”