Nano-sized robots can help kill bacteria deep inside dentinal tubules


Nano-sized robots manipulated using a magnetic field can help kill bacteria deep inside dentinal tubules and boost the success of root canal treatments, a new study by researchers at the Indian Institute of Science (IISc) and IISc-incubated startup, Theranautilus, shows.

Root canal treatments are routinely performed to treat tooth infections in millions of patients. The procedure involves removing the infected soft tissue inside the tooth, called the pulp, and flushing the tooth with antibiotics or chemicals to kill the bacteria that cause the infection.

But many times, the treatment fails to completely remove all the bacteria – especially antibiotic-resistant bacteria such as Enterococcus faecalis – that remain hidden inside microscopic canals in the tooth called dentinal tubules.

“The dentinal tubules are very small, and bacteria reside deep in the tissue. Current techniques are not efficient enough to go all the way inside and kill the bacteria,” explains Shanmukh Srinivas, Research Associate at the Centre for Nano Science and Engineering (CeNSE), IISc, and co-founder of Theranautilus.

In the study published in Advanced Healthcare Materials, the researchers designed helical nanobots made of silicon dioxide coated with iron, which can be controlled using a device that generates a low intensity magnetic field. These nanobots were then injected into extracted tooth samples and their movement was tracked using a microscope.

By tweaking the frequency of the magnetic field, the researchers were able to make the nanobots move at will, and penetrate deep inside the dentinal tubules. “We have also established that we can retrieve them … we can pull them back out of the patient’s teeth,” says Srinivas.

Tiny bots that can deep clean teeth
Left: Nanobots entering a dentinal tubule. Centre top and bottom: Schematic representation and electron microscope image of nanobot moving through dentinal tubule to reach bacterial colony. Right: How locally induced heat from nanobot can kill bacteria. Live bacteria are green and dead bacteria are red. Bottom right shows band where targeted treatment has been done in human teeth. Credit: Theranautilus

Crucially, the team was able to manipulate the magnetic field to make the surface of the nanobots generate heat, which can kill the bacteria nearby. “No other technology in the market can do this right now,” says Debayan Dasgupta, Research Associate at CeNSE, and another co-founder of Theranautilus.

Previously, scientists have used ultrasound or laser pulses to create shockwaves in the fluid used to flush out bacteria and tissue debris, in order to improve the efficiency of root canal treatment. But these pulses can only penetrate up to a distance of 800 micrometers, and their energy dissipates fast.

The nanobots were able to penetrate much further – up to 2,000 micrometers. Using heat to kill the bacteria also provides a safer alternative to harsh chemicals or antibiotics, the researchers say.

Theranautilus was spun out of several years of work on magnetically-controlled nanoparticles carried out in the lab of Ambarish Ghosh, Professor at CeNSE. His group, along with collaborators, has previously shown that such nanoparticles can trap and move objects using light, swim through blood and inside living cells, and stick strongly to cancer cells. “These studies have shown that they are safe to use in biological tissues,” says Dasgupta.

The team has tested the dental nanobots in mice models and found them to be safe and effective. They are also working on developing a new kind of medical device that can easily fit inside the mouth, and allow the dentist to inject and manipulate the nanobots inside the teeth during root canal treatment.

“We are very close to deploying this technology in a clinical setting, which was considered futuristic even three years ago,” says Ghosh. “It is a joy to see how a simple scientific curiosity is shaping into a medical intervention that can impact millions of people in India alone.”

Nanotechnology in dental care

Micro- and nanorobots are a burgeoning technology that have been studied for waste management solutions as well as for healthcare applications; their usage as antibacterial agents is well-known, and they can evade our body’s immune defenses. But few studies have looked at such nanobots in dentistry.

Publishing in Advanced Healthcare Materials, Ambarish Ghosh and his team at the Centre for Nanoscience and Engineering at the IISc developed nanobots which are small enough to fit through the dentinal tubules and reach the bacteria to kill it. These nanobots can be incorporated during the root canal treatment and controlled externally, allowing the dentist precise control when disinfecting the affected tooth.

The internal structure of a human tooth prepped for root canal treatment. On the right, a cross section of the dentine shows a tubule with bacteria embedded deep within it

“Our research involves using remotely controlled nanorobots that can be driven using innocuous low-intensity magnetic fields,” explained Debayan Dasgupta, a Ph.D. student at the time of the research, in an email. “It is much more efficient at maneuvering in hard-to-reach anatomies and can be retrieved back, unprecedented for any contemporary drug delivery technology.”

This proves to be much better than contemporary disinfection methods, as Shanmukh Peddi, dental surgeon and co-author in this study, explained: “To increase the depth of penetration of drugs, various other modalities have been implemented such as lasers and ultrasounds, but as the energy decays quickly these methods are inefficient at deeper levels of drug tissue penetration. So, current methods cannot treat deep-seated bacterial colonies that persist over time and cause complications post-treatment.”

Freshly extracted teeth from orthodontic patients were used in the study, making it an in vitro study rather than clinical trial, but the results are no less promising. As Dasgupta explained, “We demonstrated [an] established antibacterial efficacy of the nanorobots (swarm) against Enterococcus faecalis bacterium biofilms inside the human tooth, using the localized heat released from the nanobots through magnetic hyperthermia at tissues depths of 2000 microns, which is highest depth achieved by any other contemporary market technology.”

Root canal nanobot
An SEM image of a nanobot within human dentin

Peddi also stressed the importance of targeting this particular bacteria, since it is the most common cause of post-treatment infection and “a WHO priority bacteria due to its ability to become antibiotic-resistant. We use localized heat to kill these bacteria, thus eliminating the need for antibiotics.”

Furthermore, the nanobots are retrievable after use. They can simply be controlled to exit the dentinal tubules where they can be collected, a feature that is “unprecedented” according to Dasgupta.

With all the bacteria in the dentine tubules destroyed, dentists can be safe in the knowledge that the risk of post-treatment root canal failure is minimized. The next step would be to move away from in vitro studies, which the authors hope to do soon after setting up a start-up company together to collaborate with scientists at the IISc.

“[Our] next challenge involves organizing randomized controlled trials for in vivo animal studies,” said Peddi in an email, “and proving their efficacy in living systems, which will further pave the pathway for clinical translation. The startup is currently exploring other medical domains where this technology can be applied.”

Ghosh is also hopeful his team’s work can be the start of a generalized approach to “nanosurgery”, not just in the dental field. “We show nanobots [can be] manipulated inside human organs and fight deadly bacteria,” he said, adding that their work is “bringing into reality one of the long standing goals of modern nanotechnology.”

More information: Debayan Dasgupta et al, Mobile Nanobots for Prevention of Root Canal Treatment Failure, Advanced Healthcare Materials (2022). DOI: 10.1002/adhm.202200232


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