The future is already here: hybrid nanosubmarines for detecting and killing cancer cells

Collaboration between universities in the US resulted in the creation of new hybrid nanosubmarines capable of identifying and killing cancer cells, marking them with iron grains for MRI examination and phosphoric molecules for surgery

You wake up one morning and go to the doctor for your annual routine checkup. He checks your weight, pulse, blood pressure, blood cholesterol level and finally injects you with a small ampoule, filled with billions of tiny nano-submarines. The nano-submarines are dispersed in the bloodstream and probe for tumors and cancer cells. When they find such, they cling to them, penetrate them and release a deadly poison inside the cell.

To verify the success of the treatment, the doctor takes you through a fast MRI. In addition to the poison they contain, the nano-submarines also carry paramagnetic iron grains that appear on an MRI and indicate their location in the body, where they have bound to the cancer cells. The MRI shows several tumors that were too large to be destroyed by the nanosubmarines alone. There is no choice: the tumor must be analyzed and removed from the body. But even this operation, which usually requires an expert oncologist, becomes extremely simple thanks to the nanosubmarines. Each of the tiny submarines also contains phosphorous molecules, in addition to the poison and the iron grains. The doctor uses special glasses that allow him to see the tumor glowing orange inside the body, and removes or burns it with a laser without leaving even a single living cancer cell in the body.

According to all the advances in the field of nanomedicine, there is no doubt that the described future is approaching us with giant steps. Different types of nanosubmarines have already been described in the past, including iron 'nanoworms' that identify tumors and mark them for the MRI examination, nanosubmarines containing a poison that kills tumors and even nanosubmarines that glow in the dark. Now, in a combined study from the University of California San Diego, Santa Barbara and MIT, all these features have been combined together to create a nano-submarine capable of doing everything at once: stick to a tumor, secrete a toxin into its environment, mark it for detection by MRI and remove it from the body by fluorescence (phosphorus).

"The idea combines imaging agents and drugs into a protective 'mother ship' that avoids the natural processes [in the body] that would eliminate these agents if they were unprotected," says Michael Saylor, professor of chemistry and biochemistry at UC San Diego. Saylor headed the team of chemists, biologists and engineers who turned the extraordinary idea into reality. "The diameter of the mother vessels is only 50 nanometers - 1,000 times smaller than the diameter of a human hair. They are equipped with an array of molecules on their surface, which allows them to discover and penetrate tumor cells in the body."
The 'shell' of the nano-submarines consists of lipids - fatty molecules that make up the surface of all body cells. The lipids in this study were specially modified, allowing the submarines to drift in the bloodstream for many hours before being eliminated, as demonstrated in a series of experiments on mice. The ability of the submarines to evade the body's immune systems is particularly important, because it allows them to import drugs in high concentrations and over time to the tumor cells.

"Many drugs look promising in the lab, but fail in humans because they don't reach the diseased tissue in time, or in high enough concentrations," explains Sangeeta Bhatia, a physician, bioengineer, and professor of health sciences and technology at MIT, who played a key role in the development of the nanosubmarines in his lab. . "These drugs do not have the ability to evade the body's natural defenses or differentiate between the target cells and the healthy tissues. In addition, we lack the tools to diagnose diseases, such as cancer, in their earliest stages of development, when the drugs can be particularly effective."

To optimize drug delivery to cancer cells only, a protein called F3 is attached to the surface of the submarines. This protein, engineered in the laboratory of Arki Ruoslati, recognizes the cancer cells, binds to them and is transported into their nucleus together with the submarine. This protein is only the first generation of proteins that identify tumors and enable their effective treatment.

"We are now assembling the next generation of nanodevices for smart tumor detection," says Ruoslatti, a professor and biologist at the Burnham Center for Medical Research at UC Santa Barbara. "We hope that these devices will improve the diagnostic imaging of cancer and allow precise targeting of treatments for cancerous tumors."

The submarines were loaded with three different types of cargo before being injected into the mice. Two of the payloads are nanoparticles of different types: superparamagnetic iron-oxide grains, and phosphorescent quantum dots. The third cargo is doxorubicin, an anti-cancer drug. The iron nanoparticles enable detection of the submarines in an MRI, while the quantum dots can be detected using a fluorescent scanner.
"The fluorescent image provides a higher resolution than the MRI," Saylor says. "One can imagine the surgeon checking the exact location of the tumor in the body before surgery using MRI, then using fluorescent imaging to find and remove all parts of the tumor during surgery."
The members of the research group discovered to their surprise that a single mother ship can carry several grains of iron oxide, which increase its brightness in the MRI image. Despite the fact that there are already hybrid nanosystems capable of carrying different types of nanoparticles, there are very few experiments done with hybrid nanosubmarines on living organisms.

"This study provides the first example of a single nanometer material capable of delivering drugs and enabling multi-mode imaging of diseased tissue in an animal," says Ji-Ho Park, a doctoral student in Saylor's lab who participated in the study. The researchers are now working on coating the nanosubmarines with chemical recognition molecules, which will allow them to reach specific tumors, tissues and organs in the body.

For information on the website of the University of California in San Diego

On the science website:

• The wondrous journey of the human body
• Nanotechnology - a look towards the future