Odds are you’ve never heard of them, but stimuli-responsive nanobots may revolutionize medicine by allowing micro repairs and targeted drug delivery. The possibilities are amazing, including precisely controlling the release of therapeutic agents in response to specific environmental cues. Nanobots might be able to be triggered remotely to relocate to new locations upon receiving wireless signals, for example. Here are a few types of triggers that have been explored.

pH-Responsive Nanobots

pH-responsive nanobots are designed to release drugs in response to changes in pH levels, such as the acidic tumor microenvironment[1][3][5]. These nanobots can be fabricated with pH-sensitive linkers or materials that undergo conformational changes or degradation at acidic pH, triggering drug release[1][4][6]. By targeting the acidic conditions found in solid tumors, pH-responsive nanobots enhance treatment efficacy while minimizing side effects to healthy tissues[1][3][5].

Temperature-Responsive Nanobots

Temperature-responsive nanobots release drugs upon exposure to specific temperature thresholds, often associated with disease sites[5]. These nanobots can be engineered using materials that undergo phase transitions or structural changes at targeted temperatures, leading to drug release[5]. By responding to elevated temperatures, temperature-responsive nanobots enable localized drug delivery to areas of inflammation or tumors[5].

Light-Responsive Nanobots

Light-responsive nanobots employ light as a stimulus for drug release, utilizing photoactive materials or light-sensitive linkers[5]. Upon exposure to specific wavelengths of light, these nanobots undergo photochemical reactions, resulting in drug release at precise locations[5]. Light-responsive nanobots offer spatiotemporal control over drug delivery and can be externally activated, providing on-demand therapeutic intervention[5].

WiFi-Responsive Nanobots

The latest innovation in stimuli-responsive nanobots is the development of WiFi-responsive systems that can relocate to new locations upon receiving wireless signals[8]. These nanobots are equipped with wireless receivers and actuators that enable them to move in response to WiFi signals[8]. By precisely positioning the nanobots at the target site, WiFi-responsive systems optimize drug delivery and enhance treatment efficacy[8].

Ultrasound Responsive Nanobots

Ultrasound-responsive nanobots are an emerging class of nanorobots designed to be powered and controlled by external ultrasound stimulation. These nanobots typically consist of materials like gold nanowires or polymeric nanoparticles that can be propelled by the pressure gradients generated from ultrasound waves[29][32]. The directional movement of ultrasound-powered nanobots allows them to effectively penetrate biological barriers and reach target sites like tumors[29]. Additionally, the ultrasound energy can trigger the release of therapeutic payloads, such as drugs or siRNA, from the nanobot carriers[29][32]. Compared to other propulsion methods, ultrasound provides deep tissue penetration and strong thrust to overcome the complex in vivo environment[29]. However, potential side effects like oxidative stress on cells must be carefully considered when applying ultrasound to power nanobots[29][30]. Overall, ultrasound-responsive nanobots show great promise for targeted drug delivery and cancer treatment applications.

Shapes and Sizes

Stimuli-responsive nanobots can be engineered in various shapes, including spheres, rods, cubes, and even more complex structures[2][4][6]. The shape and size of the nanobots can be tuned to optimize their performance, such as enhancing cellular uptake or improving circulation time[2][4][6]. By carefully designing the nanobot architecture, researchers can create highly efficient and targeted drug delivery systems.

Mysterious dark spot near fovia caused partial obstruction of vision. From eye exam on May 20, 2021.

IMAGE: This dot (left) is a high resolution OCT scan view finder picture of what appears to be a nanobot inside of a human eyeball. It is roughly 200 micrometers (um) in size . The ophthalmologists who saw it visually (no image was taken), said was is a clump of blood cells. It could be about 20 to 40 blood cells in a clump, but it looks like more of a starfish than a clump of blood cells. Why didn’t they point the OCT at the actual clump? That is just one more mystery. Perhaps they did, but omitted that frame in the output given to the patient.

Back to our educational post about nanobots:

Shape-Morphing Capabilities: Research has shown that microrobots can change their shapes in response to environmental stimuli, which could be beneficial for pentagon-shaped nanobots to adapt to different biological environments or tasks, such as drug release[27].

IMAGE: Hey, isn’t that that the mysterious thing in the eye image? The above is a SMMF (Shape Morphing Microfish). Where are these researchers? China. If the scale is right on this, the one here is over six times smaller than what was in the eye on the OCT scanner above, so that makes the whole theory much less likely. Still, it’s a weird coincidence. Perhaps China has a secret program to nano-fish certain US persons? That would be wild speculation based on almost no evidence.

The above image is a still from a video accompanying an article titled: “Environmentally Adaptive Shape-Morphing Microrobots for Localized Cancer Cell Treatment” by the following authors: Chen Xin, Dongdong Jin, Yanlei Hu, Liang Yang, Rui Li, Li Wang, Zhongguo Ren, Dawei Wang, Shengyun Ji, Kai Hu, Deng Pan, Hao Wu, Wulin Zhu, Zuojun Shen, Yucai Wang, Jiawen Li, Li Zhang, Dong Wu, and Jiaru Chu ACS Nano, DOI: 10.1021/acsnano.1c06651

Below is the video of the SMMF in action. It can really move. I think you’d feel that. This proof of concept seems to not be self-propelled, but to be guided by a magnet. It is very hard to believe that the ability to control this remotely to a very fine degree in three dimensions currently exists, but you never know!

Current Smallest Functional Nanobots

Many of the smallest functional nanobots are designed at the nanoscale, typically around 1 to 100 nanometers in size. This small size allows them to navigate biological environments effectively, reaching areas that traditional therapies cannot. For instance, DNA origami nanobots can be constructed to perform complex tasks at the molecular level, making them suitable for precise drug delivery and biosensing applications, A 100 micrometer nanobot might seem relatively large, but it is still considered a nanobot due to its microscale size and the unique properties it exhibits at that scale.

The Usefulness of Larger Nanobots

At around 200 micrometers (0.2 millimeters), larger nanobots possess several advantages over their smaller counterparts:

Ease of Fabrication: Constructing nanobots at the 200-micrometer scale is generally easier and more cost-effective than creating devices at the true nanoscale (1-200 nanometers). This allows for more efficient mass production and wider accessibility.
Increased Payload Capacity: Larger nanobots can carry more cargo, such as therapeutic agents or imaging probes, enabling more effective drug delivery or diagnostic capabilities.
Enhanced Visibility: These microscale nanobots are more easily observable using conventional microscopy techniques, facilitating real-time monitoring and tracking of their movement and function within biological systems.
Improved Propulsion: Larger nanobots can be equipped with more powerful propulsion systems, such as magnetic or acoustic actuators, allowing for better control and navigation within the body.
Potential for Hybrid Designs: 200-micrometer nanobots can serve as platforms for integrating various components, such as sensors, drug-loaded nanoparticles, or even smaller nanobots, creating hybrid systems with enhanced functionality.

Ethical Concerns about Misuse of Stimulus Response Nanobots

Nanobots capable of responding to external stimuli raise several ethical concerns regarding their potential misuse:

Weaponization

Nanobots could potentially be weaponized to attack biological organisms at the molecular level. Armies could develop disassemblers to target physical structures or living cells. Even without considering extreme disaster scenarios, nanobots could be used to erode freedom and privacy if misused as tiny microphones, cameras or tracking devices[22].

Uncontrolled Replication

If nanobots were designed to be self-replicating and there was a problem with their limiting mechanism, they could multiply endlessly like viruses, leading to catastrophic consequences. A similar hazard is the “Gray Goo Scenario” where general purpose disassemblers get loose in the environment and start breaking down every molecule they encounter[22].

Fairness and Access

There are concerns about the equitable distribution of benefits from nanobot applications. People may doubt that everyone will have access to the benefits, suggesting the ethical principle of equity is compromised. There are also doubts about whether nanobot applications will deliver on promised benefits or be oversold[21].

Ethical Oversight

Ethical reflection and oversight must accompany nanobot research every step of the way. Factual scientific knowledge about nanobots is influenced by biases and values. Risk assessments are partly subjective and likely to be politicized. Alternative assessments are needed to capture the ethical and political values that inform nanobot policies[20].

In summary, while stimulus response nanobots hold great potential, their development must be accompanied by robust ethical analysis and governance to prevent misuse, ensure equitable access, and maintain public trust. Ongoing collaboration between scientists, ethicists, policymakers and the public is critical to navigate the complex issues raised by this transformative technology.

Top 10 Nanobot Developers

Bionaut Labs
Location: Los Angeles, USA
Website: bionautlabs.com
Shapes: Microscale robots under 1 mm, customizable shapes for specific therapies
Focus: Development of nanorobots for targeted drug delivery to treat brain diseases, including gliomas and Huntington’s disease.
Nanorobotics
Location: Hod HaSharon, Israel
Website: nanorobotics.com
Shapes: Molecular nanomachines, various configurations for targeting cancer cells
Focus: Creation of nanomachines that target and kill cancer cells using light stimuli.
AMAROB Technologies
Location: Besançon, France
Website: amarob.com
Shapes: Microbot surgical devices with flexible designs for surgical applications
Focus: Manufacturing microbot devices for intracorporeal laser surgeries.
Theranautilus
Location: Bengaluru, India
Website: theranautilus.com
Shapes: Magnetic nanobots with various geometries for oral healthcare
Focus: Development of magnetic nanobots for oral healthcare, targeting bacterial biofilms and teeth desensitization.
Microsure
Location: Eindhoven, Netherlands
Website: microsure.nl
Shapes: Robotic devices designed for microsurgical precision
Focus: Enabling robot-assisted microsurgery to improve surgical outcomes.
CureMetrix
Location: San Diego, USA
Website: curemetrix.com
Shapes: Imaging solutions incorporating nanotechnology
Focus: Development of AI-driven imaging solutions for breast cancer detection.
Senti Bio
Location: San Francisco, USA
Website: sentibio.com
Shapes: Programmable cell therapies utilizing nanotechnology
Focus: Engineering programmable cell therapies for treating various diseases, including cancer.
NanoXplore
Location: Montreal, Canada
Website: nanoxplore.ca
Shapes: Graphene-based nanomaterials in various forms
Focus: Research and development of graphene-based nanomaterials for biomedical applications and drug delivery systems.
Zymergen
Location: Emeryville, USA
Website: zymergen.com
Shapes: Bioengineered materials with nanostructures
Focus: Utilizing bioengineering and nanotechnology to develop new materials and processes for pharmaceuticals and industrial applications.
Nanosys
Location: Milpitas, USA
Website: nanosys.com
Shapes: Nanostructured materials for various applications
Focus: Development of nanostructured materials for displays, batteries, and medical diagnostics.
ACS Nano
Location: United States, Scientists World-Wide
Website: https://pubs.acs.org/doi/10.1021/acsnano.1c06651
Shapes: Nanostructures, including nanomaterials and self-assembled structures
Focus: An international forum for comprehensive articles on nanoscience and nanotechnology research, covering synthesis, assembly, characterization, and applications across chemistry, biology, materials science, physics, and engineering.

Conclusion

Stimuli-responsive nanobots represent a significant advancement in targeted drug delivery, offering precise control over drug release and localization. With the development of pH-responsive, temperature-responsive, light-responsive, and WiFi-responsive systems, researchers can tailor the nanobots to specific disease conditions and patient needs[1][3][5][8]. As this field continues to evolve, we can expect to see even more innovative designs and applications of stimuli-responsive nanobots in the future.

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