Discussions are emerging about conducting clinical trials on humans with nanorobots for medical applications. Currently, in the United States, four burgeoning companies are striving towards this aim, working to advance their nanomachines into Phase 1 studies, subsequent to laboratory research and preclinical trials on animals.

The article “Delivering drugs with microrobots“, published in Science on December 7, 2023, has recaptured the international scientific community’s attention on the practical, effective use of nanorobots in Clinical Practice and Medicine.

Its author, Bradley Nelson, a Robotics and Intelligent Systems professor at ETH Zurich, poses a straightforward question: “where are” these diminutive biocompatible machines, designed to be injected into the human body for more efficient exploration, internal repair, and precise, targeted drug delivery? Researchers have discussed them for years – he notes – yet we still do not see them progressing from laboratories to the forefront of clinical trials. How close are we to this milestone?

However, before addressing this pertinent question, a semantic clarification is necessary. Nelson uses the term “microrobot” in his paper – as he explains – because it’s the more widely used, general term. This term usually refers to robots ranging in size from a micron (a hundredth of a hair’s thickness) to a few millimeters.

Yet, if the device is smaller than a micron, it’s classified as a nanorobot (or “nanobot”) and falls under the realm of nanorobotics. This field involves creating robots ranging from 0.1 to 10 micrometers in size (a micrometer being one-thousandth of a millimeter), utilizing principles and methods from nanotechnology and nanofabrication. This is the focus of our discussion in this article.

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TAKEAWAYS

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Nanorobots in Clinical Practice and Medicine: Anticipated Healthcare Applications

The research that led to the creation of the first nanodevice, as thick as a human hair and capable of autonomous movement in fluids (powered by glucose), dates back to 2004 and is attributed to the University of California. This pioneering work in nanometric robotics immediately captured attention for creating cell-sized nanomachines that could be injected into the human body and navigate internally as a full-sized robot does in reality.

From their inception, the primary application of nanorobots has been in medicine. So much so that researchers began using the term “nanomedicine” before 2010 to describe the future use of nanorobotics for penetrating living cells to release molecules and perform tasks typically requiring invasive microsurgery.

Constructed from synthetic, biological materials (like DNA filaments), or both (though most are magnetically driven), nanobots can transport and release drugs at specific body sites (known as “drug delivery“). They also have potential for restructuring tissues, suturing blood vessels, exploring arteries and organs en masse, and dissolving blood clots in stroke patients’ brains.

However, the most compelling therapeutic area for nanorobotics has always been oncology. The aim is to surpass classical chemotherapy – deemed too invasive and aggressive – by utilizing nanorobots’ size to target cancer cells, even in hard-to-reach areas, and deliver drugs directly to the tumor. This method bombards the tumor from within while preserving the surrounding healthy cells and tissues.

These are the expected tasks and functionalities of such nanodevices in routine clinical practice. And the wait for their implementation might soon be over.

Startups Progressing Towards Human Clinical Trials

“How long until we transition from laboratory experimentation to clinical trials?” is the question posed by Bradley Nelson in his article on nanorobots supporting medicine.

Nelson, a professor at ETH Zurich, is optimistic about these devices reaching hospitals. Some have already advanced from laboratory settings to preclinical trials on larger animal models, including pigs. In the United States, at least four startups are developing nanobots for human clinical trials to assess their safety and effectiveness.

One such company is Bionaut, based in Los Angeles, which invested 43 million dollars in January 2023 to progress its nanomachines to Phase 1 studies, coinciding with tests on the human body.

Specifically, the American company is focusing on developing and producing nanorobots, as large as a pencil tip, tasked with targeted drug delivery for treating a rare genetic condition known as “Dandy-Walker Syndrome”, identifiable even during embryonic development.

This syndrome leads to severe cerebellum malformation and fluid blockage in brain cavities in affected children. The nanodevice, still under development, aims to precisely release the active ingredient to the cysts obstructing spinal fluid flow in the brain and puncture them.

This pioneering therapeutic approach, with its historical significance, promises to revolutionize the management of rare genetic diseases.

Future Directions in Nanorobot Research

Regarding nanorobots in medicine, while the most eagerly awaited applications in daily clinical practice are as described earlier, two studies in 2023 have ventured into previously uncharted territories of nanorobotics engineering, related to neurology and in vitro fertilization.

On November 30, 2023, as Nelson describes, Advanced Science published an article (“Motile Living Biobots Self-Construct from Adult Human Somatic Progenitor Seed Cells“) detailing Tufts University researchers’ development of a nanobot using tracheal cells from volunteer patients.

The choice of the trachea is due to its internal “waving cilia” structure, designed to capture external microbes and materials, which proved beneficial in designing an organoid with outward-facing cilia.

These nanorobots, based on the shape and coverage of their cilia, could move in a straight line, circle, or oscillate. However, an unforeseen discovery was made when the team ran a tiny metal rod along neurons in a lab experiment: the nanobot composed of waving tracheal cilia “invaded the area and triggered new neuron growth.”

This pioneering research opens up possibilities for growing neurons in the brain’s damaged areas using normal, unmodified tracheal cells capable of autonomous movement.

In February 2023, a paper titled “Medical microrobots in reproductive medicine from the bench to the clinic“, published in Nature Communications, described a German team’s development of a magnetically guided nanorobot for potential use in in vitro fertilization.

These nanomachines could safely return externally fertilized embryos to the uterus, potentially boosting implantation success rates. Nelson notes that the study’s authors envision future magnetically guided nanorobots transporting fertilized embryos, releasing them into the patient’s body, and then naturally degrading.

Challenges Past and Present

Since the initial research in 2004, medical nanorobot researchers have been clear about their goals, especially concerning the size of nanomachines for injection into the human body. They’ve also focused on solving movement challenges in various bodily fluids and tissues and addressing biodegradability.

Creating increasingly smaller nanobots for more precise human organ and tissue analysis, thereby avoiding invasive biopsies, remains the primary challenge for nanorobotics engineers.

Yet, Nelson warns of the viscosity of human blood, which can hinder the movement of smaller nanodevices, especially against rapid blood flow.

Another critical issue is the biodegradability of nanorobots in the bloodstream and, relatedly, the safety of the materials used in their fabrication, particularly regarding potential toxicity.

On the verge of human clinical trials, regulatory hurdles also loom, particularly for nanorobots’ drug delivery function. The combination of drug and device is a focal point:

“Even if the drug is already well-known and authorized, the ‘in-situ’ release method, involving significantly higher concentrations than traditional administration, will prompt local Regulatory Authorities to require additional studies. This will, in turn, prolong the wait for human organism experimentation,” Nelson concludes.