Nanobot: Futuristic Intelligent Doctor

Tokyo, Japan: In the year of 1966, the future of nanobots (nano-robot) was first featured in a popular Hollywood Sci-Fi movie, “Fantastic Voyage”. The concept of the movie was a submarine and its crew was shrunken to the size of a microbe in such a way that they can be injected into the bloodstream of an injured scientist whose brain was blocked and stopped working by a deadly blood clot. Based on the reel man’s imagination, the real life scientists have been fascinated by the advancement of technology to do revolutionary innovations in the medical science. The best example is to treat inoperable tumours in the brains with the help of nanobots. Meanwhile, the concept of these nanobots was also introduced in the story lines of other popular Hollywood movies, such as Seven of Nine in Star Trek: Voyager, Innerspace, I Robot, Hulk, Iron Man, Terminator 3, G.I joe-The Rise of Cobra, Ghost in a Shell, The Avengar-Infinity War. Prof. Gao Wei of Carolina Institute of Technology inspired a lot based on the movie “Fantastic Voyage” and developed a microbot that can be guided towards specific parts of the digestive tract to treat the tumours. Even he stated, in the future, a tiny machine would be able to travel inside the human body to sense the particular diseased area, deliver the drugs with high precision, and perform surgery or stimulate the neuron in the brain [1]. The idea of the nanobot was again influenced by a novel “Prey” by Michael Crichton in 2002 where he had mentioned two important terms, “Nanobots” and “Assembler”. Nanobot is a miniaturised robot that performs certain functions, whereas “Assembler” can build new structures and is able to multiply himself if he knows the right blueprint. Soon both of these ideas were merged to form a new thought named as “Grey Goo” which extinguishes all life on earth by multiplying themselves in an uncontrolled manner. The scientific discussions of the novel were essentially argued by two well renowned scientists, Erik Drexler and the Nobel laureate Richard Smalley. Their controversial discussions even gave more in-depth findings on the function of nano machines. Drexler claimed that depending on the equipment this tiny nanomachines could be assembled themselves to move like an organism to do different work properly and could even allow to reproduce further on the addition of a definite mechanism. On the other hand, his hypothesis was strongly opposed by Richard Smalley who had stated the fact that these tiny machines would not work because of Van der Waals forces between the atoms would not allow the machine parts to move. The strong gravitational forces between the matters would not allow independent nanobots to be assembled in small structure, although it could be possible within micro or millimetre sized structures.

There are various components required to build a nanobot including, “shell” (principle component of the machinery system),  “motor” (driving machine), “energy source” (to operate the machine),“sensor” (detect the environment to navigate the machine), and “payload” (a chamber built inside the machine to load the drugs for targeted delivery approach). In current scenario, there are plenty of technological developments are going on throughout the world’s top most research laboratories and it is reasonable to expect that use of nanobots may take a pivotal role for human disease cure in next decade. Prof. Sun and his team from Beijing’s Tsinghua University have developed a 3D printed nanoscale robot (trial version) to repair the meniscus, the thin fibrous cartilage in between knee joints. By targeting drug delivery approach, a small dose of drugs can be reached to the injured knee than a bigger dose of medicine swallowed by mouth [2]. Dr Jinxing Li, Post Doctorate Fellow at Standford University developed a drug delivery system based on micromotors powered by stomach acid [3]. In a recent work, scientists from the Arizona State University in collaboration with researchers from the National Center for Nanoscience and Technology (NCNST), of the Chinese Academy of Sciences, have successfully developed a DNA nanobot name as “DNA Origami”. In this study, they have fabricated thrombin (anticoagulating agent) loaded DNA nanobot and injected into the blood stream to shrink the cancer cell by blocking tumour blood flow and ultimately cause cancer cell death [4]. Researchers from Massachusetts Institute of Technology have created cell-sized nanobots that can sense their environment, form cluster together. Moreover, this can be controlled by magnetic field operated from outside. [5] Scientists from the University of Pennsylvania have designed catalytic antimicrobial robots (CARs) which could even eliminate dental plaque via magnetic field operating system [6]. Even many of these nano designs inspired by nature to swim, crawl or walk and they could be powered by heat or electricity within the body. [7] A group of researchers from ITMO University, Russia has discovered a new concept of a drug delivery approach against cancer. Their innovative concept is based on an idea in a “theranostic” approaches (combined effect of therapeutic and diagnostic) on simultaneous diagnostic of a disease [8]. Such DNA based nanobots consist of two parts: a detection one and a therapeutic one. Detection part of the nanobot detects the pathogenic cells in terms of incorrect RNA molecule by chemically binding with substance artificially introduced into the cell. Whereas, the therapeutic part destroys the pathogenic RNA strand to prevent the production of harmful proteins, which inhibits the multiplication of the cancerous cells. In India, a research team from both Maharashtra Institute of Medical Education and Research and MIT World Peace University, Pune have done an excellent in-vitro study on multi component magnetic nanobot designed with chemically

conjugating magnetic Fe₃O₄ nanoparticles (NPs), anti-epithelial cell adhesion molecule antibody (anti-EpCAM mAb) to multi-walled carbon nanotubes (CNT) loaded with an anticancer drug, doxorubicin hydrochloride (DOX). Their work reveals that the multicomponent nanobot’s design represents a promising strategy in targeted cancer therapy [9]. In other hand, medical professionals/ Surgeons are also constantly looking for minimal invasive ways to treat their patients with faster recovery, as there are usually fewer complications in the postoperative methods. The potential of these nanobots in surgery is huge. Eye surgeons can perform eye surgeries by tiny microneedles injected through a standard needle into the eye and this whole process can be directed by using a specialised magnetic field [10]. For the treatment of cardio vascular diseases, corkscrew chain of iron oxide beads are injected into the bloodstream to clear the blocked arteries (work done by engineers of Drexel University) [11]. Nanobots resembling unfolded cubes made of

elastic polymer grab tissue samples by folding up and collect the sample for biopsies [12]. Nanopatch vaccines made up of thousands of silicon microneedles which offer similar immune response with a smaller dose of vaccine can eliminate the need for refrigeration. Smart bandage made from hydrogel, can be left on infected area until they dissolve and release the antibiotics as needed to heal. Vibrant capsules promote muscle contraction to quick start digestion. Even it treats IBS (irritable bowel syndrome) patients to recover from constipation without any laxatives. In 2001, the first FDA (US. Food and Drug Administration) approved ingestible camera attached smart pill name as PillCam has been launched. Another smart pill developed in US, contains a sensor which fetches the data through a patch worn by the patient. The imprinted App tracks the drug, dosage and time, which can be shared with both doctors and patients. Atmo gas capsules diagnose Gastrointestinal disorder and colon cancer by detecting the levels of oxygen, hydrogen and carbon dioxide, which may enter the capsules through an outsider permeable membrane surrounded it. Even this level of oxygen allows the researchers to navigate the capsule’s location.   It is highly mentioned that by 2024, the global market for nanotech will exceed $125B and by 2025, the global smart pill market will reach $650M [13]. The scenario of medical science is expected to completely change in next decades where indigestible capsules, nanobots containing sensors, cameras, and microprocessor units will be used as a therapeutic approach. In future, surgical nanobots, programmed by a human, may act as an autonomous on-site surgeon inside the human body. These nanobots will help the surgeon’s life easier from the use of surgical tools and may lead to planned treatment with more precision and better execution.

Sources:

1. Micro/nanorobots for biomedicine: Delivery, surgery, sensing, and detoxification, Jinxing Li, Berta Esteban-Fernández de Ávila, Wei Gao, Liangfang Zhang* and Joseph Wang*, Science Robotics  01 Mar 2017:Vol. 2, Issue 4, eaam6431, DOI: 10.1126/scirobotics.aam6431
2. https://www.todayonline.com/these-tiny-robots-are-turning-science-fiction-medical-reality
3. Micromotor-enabled active drug delivery for in vivo treatment of stomach infection BEF de Ávila, P Angsantikul, J Li, MA Lopez-Ramirez, Nature communications 8 (1), 1-9
4. Tasciotti, E. Smart cancer therapy with DNA origami. Nat Biotechnol 36, 234–235 (2018). https://doi.org/10.1038/nbt.4095
5. Nanoparticles take a fantastic, magnetic voyage Tiny robots powered by magnetic fields could help drug-delivery nanoparticles reach their targets. Anne Trafton | MIT News Office Publication Date:April 26, 2019, https://news.mit.edu/2019/nanoparticles-magnetic-robots-0426
6. Catalytic antimicrobial robots for biofilm eradication, Geelsu Hwang1,*,Amauri J. Paula1,2,*, Elizabeth E. Hunter3, Yuan Liu1, Alaa Babeer1,4, Bekir Karabucak4, Kathleen Stebe5, Vijay Kumar3, Edward Steager3,† and Hyun Koo1,†, Science Robotics  24 Apr 2019: Vol. 4, Issue 29, eaaw2388, DOI: 10.1126/scirobotics.aaw2388
7. Palagi, S., Fischer, P. Bioinspired microrobots. Nat Rev Mater 3, 113–124 (2018). https://doi.org/10.1038/s41578-018-0016-9
8. Aleksandr A. Spelkov  Ekaterina A. Goncharova  Artemii M. Savin  Dr. Dmitry M. Kolpashchikov, Bifunctional RNA‐Targeting Deoxyribozyme Nanodevice as a Potential Theranostic Agent,13 January 2020 https://doi.org/10.1002/chem.201905528
9. Andhari, S.S., Wavhale, R.D., Dhobale, K.D. et al. Self-Propelling Targeted Magneto-Nanobots for Deep Tumor Penetration and pH-Responsive Intracellular Drug Delivery. Sci Rep 10, 4703 (2020). https://doi.org/10.1038/s41598-020-61586-y
10. https://www.intelligentliving.co/nanobots-swim-eye/
11. https://www.smithsonianmag.com/innovation/tiny-robots-can-clear-clogged-arteries-180955774/
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13. https://www.roboticsbusinessreview.com/news/infographic-nanobots-and-nanotech-deliver-medicines-future/