The collective movement of nanorobots observed in vivo

Nanobots are machines whose components are located at the nanoscale (one millionth of a millimeter) and can be designed to move autonomously in liquids. Although still in the research and development phase, significant progress is being made towards the use of nanorobots in biomedicine. Their uses are varied, from the identification of tumor cells to the delivery of drugs at specific locations in the body. Nanorobots powered by catalytic enzymes are among the most promising systems because they are fully biocompatible and can use “fuels” already in the body for propulsion. However, understanding the collective behavior of these nanorobots is essential to move on to their use in clinical practice.

Now, in a new study published in the journal Science Robotics, researchers led by ICREA Research Professor Samuel Sánchez and his team “Smart Nano-Bio-Devices” at the Institute of Bioengineering of Catalonia (IBEC), together with the Radiochemistry & Nuclear Imaging Lab group of CIC biomaGUNE led by Jordi Llop and the Universitat Autònoma de Barcelona (UAB), have succeeded in observing in vivo the collective behavior of a large number of autonomous nanorobots in the bladder of living mice using radioactive isotope labeling.

“The fact that we’ve been able to see how nanorobots move together, like a swarm, and track them in a living organism, is important, as millions of them are needed to treat specific pathologies, such as cancerous tumors,” said Samuel Sánchez, principal investigator. at IBEC.

“We have shown for the first time that nanorobots can be monitored in vivo via Positron Emission Tomography (PET), a highly sensitive, non-invasive technique used in the biomedical environment,” said Jordi Llop, principal investigator at Radiochemistry & Nuclear Imaging Lab. from CIC biomaGUNE.

To do this, the researchers first conducted in vitro experiments, in which they monitor the nanorobots by means of optical microscopy and positron emission tomography (PET). With both techniques they were able to observe how the nanoparticles mixed with the liquids and were able to follow complex paths together. The nanorobots were then administered intravenously to mice and finally introduced into the bladders of these animals. Because nanorobots are coated with an enzyme called urease, which uses the urea from urine as fuel, they collectively swim and induce fluid flows in the bladder.

Collective movements similar to flocks of birds or schools of fish

The team of scientists found that the distribution of nanodevices in the bladder of the mice was homogeneous, indicating that the collective movement was coordinated and efficient. “Nanorobots exhibit collective movements similar to those in nature, such as birds flying in flocks or the orderly patterns that schools of fish follow,” explains Samuel Sánchez, ICREA Research Professor at IBEC. “We have seen that nanorobots that have urease on the surface move much faster than nanorobots that don’t. It is therefore a proof of concept of the original theory that nanorobots will be better able to reach a tumor. and penetrate them, ”says Jordi Llop, principal investigator at CIC biomaGUNE.

This study demonstrates the high efficiency of millions of nanoscopic devices to move in a coordinated manner in both in vitro and in vivo environments, a fact that represents a fundamental advance in the race of nanorobots to become key players in high-precision therapies and treatments. Future applications in medicine of these nanoscale devices are promising. It has also been shown “that the movement of these devices can be tracked using imaging techniques that can be applied to the in vivo environment, in other words, they can be applied in laboratory animals and have the potential for transmission to humans,” says Cristina Simó, one of the study’s first authors and a researcher in the CIC biomaGUNE group.

“This is the first time that we have been able to directly visualize the active diffusion of biocompatible nanorobots into biological fluids in vivo. The ability to monitor their activity in the body and the fact that they show a more homogeneous distribution would revolutionize the way we understand. Nanoparticle-based drug delivery and diagnostic approaches, ”said Tania Patiño, co-corresponding author of the paper.

Nanobot swarms can be especially useful in viscous media, where drug delivery is often limited by poor vascularization, such as in the gastrointestinal tract, eye, or joints. “Since different enzymes can be incorporated into the small engines, nanorobots can be adapted to the part of the organism by adapting the device to the accessible fuel in the environment in which they need to move,” concludes Professor Sánchez.