INTRODUCTION:

The area of nanorobotics is multidisciplinary, encompassing not just nanorobotics but also different aspects of material science, biomedical engineering and nanotechnology. Nanorobots are machines with nanoscale intelligence, actuation, sensing, signaling, information processing manipulability, and collective behavior. Nanorobots show promising effect in a variety of applications including manufacturing, material removal, information security and micro-assembly, as well as localized diagnosis, targeted dosage delivery and the implantation of active devices. Nanorobotics is a rapidly developing field with the potential to revolutionize targeted drug delivery in the field of medicine.^1,2

HISTORY:

In his remarkably prescient 1959 talk "There's Plenty of Room at the Bottom," the late Nobel in Physicist Richard P. Feynman recommended using machine tools to produce smaller machine tools, which would then be used to make even smaller machine tools, and so on down to the atomic level. It determines which valve is malfunctioning and uses a little knife to cut it out. Small machines may be implanted in the body to support malfunctioning organs. Feynman explored the prospect of creating an object capable of maneuvring at the level of biological cells.^3,4

STRUCTURE OF NANOROBOT:

A magnetic helical nanorobot consists of at least two components: a helical body and a magnetic substance. The helical body gives the nanorobot a structure that allows for translation along the helical axis. Nanorobots can be constructed using most of the substances; therefore, the manufacturing method varies depending on what type of material is being used. Many nanorobots are composed of both organic and inorganic components. ^5,6

Structure of Nanorobot:

Objectives of nanorobots in Drug Delivery:

· Increased surface area and volume allows regulated distribution of higher drug payloads.

· Simple surface functionalization using ligands and biomolecules.

· Constant monitoring of the body and feedback.

· To eliminate malignant cells without harming the normal cells.^7,8

LIMITATIONS OF NANOROBOTS

· Surface modification of nanorobots is extremely challenging, as is their traversal inbody.

· Nanorobot movement in biological fluids is complex and material-dependent.

· Nanorobots are still limited for usage because of their low biocompatibility or biodegradability, since the human body recognises them as foreign particles.

· Nanorobots therapeutic and diagnostic operations are time consuming.

ADVANTAGES OF NANOROBOTS

· The nanorobot drug delivery technology increases bioavailability.

· Nanorobots can be controlled by an external computer via nanorobots to fine-tune the amount of medicine released, frequency of dosing and release timing.

DISADVANTAGES OF NANOROBOTS

· The nanorobots design, components and assembly costs are extremely high.

· Electrical systems can generate stray fields in biology, which can activate bioelectric-based molecular recognition mechanisms and cause serious cellular damage. ^9,10

CLASSIFICATION OF NANOROBOTS:

Nanorobots are broadly classified depending on their form, function, propulsion methodand biohybrid mechanism.

Morphological Classification:

Morphologically, nanorobots are divided into four types depending on geometry and synthesis.

· Sphere dimers: It consists of two sections. One half is composed of a silica sphere, while the other is constructed of platinum spherical. Thermal annealing combines both portions into a single unit. Sphere dimers are created by surface articulating silica nanoparticles with platinum placed on one side.

· Janus particles: Janus particles are formed by layering various metals over mesoporous silica nanoparticles. They can navigate thanks to the oxygen bubbles that are generated. The platinum layer decomposes hydrogen peroxide, resulting in the formation of oxygen bubbles.

· Hollow nanorobots: These are created by introducing catalysts into hollow particles. It resembles a tubular rocket-like structure with a set speed. Hollow nanorobots are created using advanced atomic layer deposition techniques. This approach was utilized to develop 100 nm nano rockets. Hollow nanorobots are made up of platinum in the inner shell and titanium dioxide (TiO2) in the outer shell.

· Nanorobots with intrinsic asymmetry: Topological asymmetry is employed to provide self-propulsion effects in nanorobots. Because nanorobots are inherently asymmetric, enzyme-powered nanomotors exhibit increased diffusivity.

Functional Classification:

1. Chemically powered nanorobots use internal energy sources such as glucose, urea, and hydrogen peroxide to navigate.

2. Biohybrid systems incorporate non-living components into Nanorobots and are dPivided into three basic categories based on how they perform.

Propulsion Mechanism Based Classification:

Nanorobots are classed according to their propulsion mechanism and the type of power source. Propulsion-based nanorobots are:

1. Exogenous power-driven nanorobots

2. Endogenous power-driven nanorobots

· Exogenous power driven nanorobots: Nanorobots with much functionality rely on external power sources, such magnetic fields, light energy, and ultrasonic energy, to complete their activities.

· Magnetic field propelled nanorobots: Magnetic fields have unique properties such as powerful driving force, and navigation control, and are non-invasive to the human body. It is effectively used to propel nanorobots in a non-contact way and deliver medications to the desired location

· Light energy propelled nanorobots: Nanorobots move via light irradiation or photocatalysis methods. They start the conversion of light energy to mechanical energy, which causes heat and chemical reactions. The energy liberated during these processes is used to navigate nanorobots.

· Ultrasound energy-propelled nanorobots: Ultrasound has a good penetrating ability and strong adaptability, propelling nanorobots towardtumor cells and enhancing drug uptake by tumor cells.

· Endogenous power-driven nanorobots: In this situation, nanorobots will use biological fuels as their power source. Examples of biological fuels include hydrogen peroxide, urea, glucose, and adenosine-5-triphosphate (ATP). Endogenous power enables nanorobots to navigate autonomously by using their fuel.

· Chemical reaction propelled nanorobots:

Hydrogen peroxide may be degraded into water and oxygen in the presence of a peroxidase enzyme, and the generated oxygen bubbles can be used to propel nanorobots.

Urea is hydrolyzed in the presence of a urease enzyme. During hydrolysis, it is transformed into ammonium and bicarbonate ions. The quicker diffusion of ammonium ions can create a local electric field. This electric field promotes the diffusion of particles. In the presence of the enzyme glucose oxidase, glucose is transformed into D-glucono-1,5 lactone and hydrogen peroxide. Hydrogen peroxide can be used in conjunction with enzymes like catalase to power nanorobots.

· Enzyme propelled nanorobots: Enzymes involved in catalytic reactions produce oxygen bubbles, which serve as a driving force for nanorobots. Oxidoreductase enzymes function as catalytic engines in nanorobots. Glucose oxidase enzyme converts glucose to gluconic acid and hydrogen peroxide. Catalase enzyme converts hydrogen peroxide to water and oxygen. This oxygen aids the navigation of nanorobots. Urease is an enzyme involved in the conversion of urea to carbon dioxide and ammonia.

Biohybrid Classification:

Biohybrid nanorobots are small devices made up of biological components (such as DNA, enzymes, cytomembranes, and cells) and artificial components (such as inorganic or polymer particles). They can accomplish a variety of functions, including single cell manipulation, cell microsurgery, and targeted medication delivery

· DNA based nanorobots:

DNA origami is used to create DNA nanorobots. This technique creates DNA nanostructures by repeatedly folding single-stranded DNA and anchoring the structure with oligonucleotides. Biohybrid magnetic microrobots are created by combining DNA flagella with magnetic iron oxide particles.

· Leukocyte based nanorobots:

Macrophage-based biohybrid nanorobots, also known as immunrobots, deliver anticancer medications to tumours and are useful in targeted immunotherapy. Neutrophil-based biohybridnanorobots, known as neutrobots, transport medications to malignant glioblastoma. The advantage of nanorobots is their ability to evade phagocytosis and elimination by the mononuclear phagocyte system.

· Sperm based nanorobots: Male reproductive cells are known as sperms, and they feature a tail called the flagellum. Motile sperms are turned into robotic micro swimmers known as spermbots. Sperm-based medication delivery systems can use

sperm rheotaxis and thigmotaxis to deliver pharmaceuticals to their intended target sites.

· Magnetotactic bacteria-based nanorobot:

Bacteria-based biohybrid microswimmers are known as bacteriabots. Motile E. Coli MG1655 is utilized to adhere to epithelial cells and deliver drugs to them in the urine and gastrointestinal systems. Bacteriabots are employed to deliver anticancer medications such as doxorubicin to the targetregion.

MECHANISM OF NANOROBOTICS:

If any obstacles come nanorobots of proximity sensors sense both moving and non-moving obstacles that hinder them in their pathway, Nanorobots wait for 0.0025 milliseconds and select a new path for their traversal. Nanorobots after reaching the target site, deliver drugs by utilizing internal and external sources. Once the target is achieved, they will be removed from the body through human excretory channels. In some cases, they can also be removed by active scavenger systems, which are known as nano terminators.

Preparation Methods for Nanorobots:

Nanorobot manufacturing can be done following the below methods.

1. Physical vapor deposition technology: Physical vapor deposition must be carried out in an ultra-clean vacuum atmosphere. The hefty target is first converted into gaseous atoms and molecules, which are then deposited on the sample surface to produce nanofilms.

2. Self-winding technology: The TiO₂/Pt bifunctional film microsphere robot was produced in batches, and its "start and stop" functions were managed using chemical and optical synergy. The self-coiling technology is to deposit multi-layers of different materials, and then following the wet etching of the sacrificial layer, the asymmetric stress is relieved. This technology isused to form the coiling of various inorganic material (Pd/Fe/Pd, TiO2, ZnO, Al2O3, C, etc.,) films.

3. Laser direct writing 3D printing technology: The optical polymerization effect is used in 3D printing to process any 3D microstructure with high precision and the nanorobot can be successfully driven through physical vapor depositionof various elements (Ni, Fe, and Fe3O4).

4. Electrochemical template deposition technology: Electrochemical deposition offers the advantages of being simple to use and inexpensive, making it ideal for the development of nanorobots. Nanorobots of various shapes (tubular, rodand spiral) can be deposited.

5. Wet chemical synthesis: The primary step of wet chemical synthesis is to decrease the target materials compound solution to simple forms such as spherical, rod-like and peanut-like forms. For example, to create magnetic peanut-like nanorobots, Na₂SO₄ was heated in an electric oven at 100^◦C for seven days^[5-10

NANOROBOTS IN THE FIELD OF MEDICAL SCIENCE

1. NANOROBOTS FOR DIAGNOSIS: Researchers has demonstrated that nanorobots perform important activities in the fields of purification, detoxification and sensory detection.

· Sensing Detection: Nanorobots can mix with fluids and activate target receptors, allowing for medical diagnosis. Nanorobots can selectively recognize metal ions, bacterial toxins, proteins, cells and so on, providing precise pre-treatment screening for disease treatments. Accurate detection of metal ions in the blood can help preserve human health by preventing excessive metal ion concentration. Thenanorobot selectively monitors the concentration of copper ions in the blood based on changes in fluorescence signals.

· Imaging of Medical Nanorobots: Because of the high space-time, a primary clinical application for medical nanorobots is to monitor individuals or groups. The ability to be easily discovered and guided in the body, as well as provide signals to promote trigger release and medical imaging. For example, the nanorobot is easily identified in the in-vivo environment at a penetration depth of 2 mm, and its real-time position in a vein is tracked using optical coherence tomography imaging to offer feedback on the nanorobot movement in-vivo.

2. NANOROBOTS FOR DISEASE TREATMENT: In recent decades, the therapeutic potential of drug delivery systems utilizing nanoparticles has gained significant attention in the scientific community. The limitations of current drug delivery systems lie in their inability to accurately target specific locations and permeate barriers, thereby hindering the effective delivery of therapeutic agents to localised areas. Compared with nanoparticles, the controllable movement of nanorobots can complete the drug delivery from single cells to local tissues/organs at a cross-scale local area to summarize, the newly designednanorobot boasts an impressive propulsion system, precise navigational capabilities, and a controlled mechanism for loading and releasing, thereby opening up vast possibilities for its application across various domainsin targeted therapy.

· DRUG CARRIERS: In traditional therapies, the common approach is to repeat the medicine in large dosages if the desired therapeutic effect is obtained, but this is likely to increase toxicity and adverse effects. The precise delivery potential of nanorobots at the target area is predicted to alleviate the toxicity associated with excessive drug use. Ultrasound-mediated therapy can reduce the toxic effects of the drug because the nanorobot can be precisely directed to the target position and the loaded dose can be selectively released by ultrasound focus.

3. TARGETING DRUG DELIVERY SYSTEMS FOR TUMOR

· PASSIVELY TARGETED DRUG DELIVERY SYSTEM: Passively targeted drug delivery systemsfor tumour therapy rely primarily on the enhanced permeability and retention effect, which is heavily influenced by the unique pathophysiological characteristics of tumour, nanomaterial properties and blood circulation parameters. In general, tumours have the following four basic pathophysiological features: Extensive angiogenesis, Lymphatic drainage/recovery system, Significant increased production of permeability mediators, Abnormal vasculature.

· ACTIVE TARGETED DRUG DELIVERY SYSTEM: Active targeted drug delivery systems are based on the interaction of connected high-affinity ligands and cognate receptors, with the ligands preferentially binding to receptors on target cells. These employed a variety of ligands, includingsmall molecules (e.g., FA) as well as macro-molecules (e.g., Peptides). More importantly, some advanced active drug carriers can achieve environmentresponsive or controllable drug delivery and transport nanocarriers to target sites when exposed to endogenous (pH, hypoxia, etc.,) and exogenous stimuli. Eg: ultrasound, light, heat and magnetic field.^10-12

APPLICATIONS OF NANOROBOTS

· Nanorobots in cancer detection and treatment: The early detection of cancer can lead to a successful treatment and a potential cure. Nanorobots aid in the early diagnosis of cancer because nano sensors can detect tumorproducing cells at an early stage. Chemotherapy involves side effects because current anticancer drug delivery systems lack intrinsic navigation for long-term circulation, targeting, localised drug delivery and tissue penetration. Nanorobots self-navigational functions enable accurate cell targeting, tissue penetration, and therapeutic efficacy.

· Nanorobots in diagnosis and testing: Micro syringes and catheters are utilized to deliver surgical nanorobots into the human circulatory system. Surgical nanorobots function as semi-autonomous on-site surgeons within the human body, programmed or guided by a human surgeon. Nanorobots can aid in the early detection of diseases at the cellular and molecular levels, as well as the collection of biological samples and tissue fluids for micro-analysis.

· Nanorobots in gene therapy: Gene therapy offers the potential to change a person's DNA and heal or cure genetic illnesses. Gene therapy works by replacing a disease-causing gene with a healthy copy, inactivating a disease-causing gene or introducing a new or modified gene.

· Nanorobots in regenerative medicine and cell therapy: Regenerative medicine helps in regenerating human cells to restore normal function. Regenerative medicine and cell therapies include usage of stem cells for tissue regeneration.

· Nanorobots in wound healing: Healing chronic wounds on their own is quite tough. Chronic wound healing relies heavily on epidermal growth factors. Chronic wound healing is hampered by biological systems that are faulty or have low coagulation factor levels. In such instances, nanorobots serve as carriers for growth and clotting factors and the successful distribution of these factors to chronic wound sites promotes speedy and effective wound healing.

· Nanorobots in dentistry: Nanorobotic dentifrices were used in dental preparations such as mouthwash, medicated paste and dental gels. They use specialised motility mechanisms to penetrate sublingual surfaces and eliminate harmful germs. A colloidal suspension enriched with nanorobots will be injected into the afflicted area to induce anaesthesia in the patient's gingival region.

· Nanorobots in haematology: Nanorobots offer a variety of uses in haematology. Respirocytes are artificial mechanical red blood cells that can perform various roles while flowing through the bloodstream.

· Nanorobots in vascular therapy: Nanorobots have proven to be invaluable in screening and monitoring chronic life-threatening conditions, including brain aneurysms, unstable atherosclerotic lesions and lung cancer. Nanorobots have potential applications in vascular treatment.^13-15

CONCLUSION:

Nanorobots have been used as diagnostic tools to detect ion content in the human body and as biosensors; as imaging tools, relying on light, sound, magnetism and other means of in-vivo and in-vitro imaging; as a means of transport load and transport drugs, biological reagentsand live cells, among other things; and as surgical tools to examine tissues and eliminate cancer cells and bacteria. This study provides an overview of nanorobots functioning processes and uses in drug delivery. This study also concentrates on the latest development in nanorobotics for therapeutic applications, surgical interventions, diagnostic methodologies and medical imaging techniques. Nanoroboticswill eventually evolve into modern medicine and have the potential to improve people's lives. Nanorobots are programmed to complete certain biological activities, which have potential use in all areas of medicine. Nanorobots have the possibility to extend therapeutic options while also improving the efficacy of current tr

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Received on 08.10.2024 Revised on 03.12.2024

Accepted on 11.01.2025 Published on 27.02.2025

Available online from March 05, 2025

Asian J. Pharm. Tech. 2025; 15(1):95-100.

DOI: 10.52711/2231-5713.2025.00016

This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License. Creative Commons License.