Nanobots for Medicinal Applications

Review Article

Austin J Nanomed Nanotechnol. 2023; 11(1): 1067.

Nanobots for Medicinal Applications

Smrutimedha Parida1; Anil Ramdas Bari2*

¹School of Chemical Sciences, NISER, Odisha, 752050, India

²Department of Physics, Arts, Commerce and Science College, Bodwad, Maharashtra, 425310, India

*Corresponding author: Anil Ramdas Bari Department of Physics, Arts, Commerce and Science College, Bodwad, Maharashtra, 425310, India. Tel: +91 9421523832 Email: anilbari_piyu@yahoo.com

Received: April 07, 2023 Accepted: May 11, 2023 Published: May 18, 2023

Abstract

The applications of nanotechnology have increased exponentially in the field of medicinal chemistry with the implementations of nanorobotics. Nanobots provide one of the most promising areas of nanotechnology spreading its roots to applications in various fields including medical imaging, drug delivery and even in the development of Nanobots have the advantages of small size, low weight, large thrust-to-weight ratio, high flexibility, and high sensitivity. The applications of nanobots are varied and are being explored in various fields. The aim of this review is to offer an overview to the emerging field of nanorobotics within medicinal chemistry and their applications for diagnosis, treatment and prevention of various diseases. It provides a comprehensive overview of the development of nanobots. The key components of the robots and the types of nanobots are discussed separately. The review also focuses on the disadvantages and the challenges in the development of nanobots for their specific causes. And finally, the efforts and measures that can bring us steps closer to the dream of catching up with our fantasies of developing tiny robots that could roam about inside our bodies, delivering drugs with unprecedented precision, and hunting down and destroying infected cells and most importantly science fiction becoming scientific fact are discussed.

Keywords: Nanomedicine; Nanobot; Nanomotors; Sensors; DNA nanorobot; Targeted drug delivery; Precision surgery

Introduction

Nanotechnology makes it possible to manipulate matter at the atomic and molecular scale to design materials with remarkably diverse and advanced properties. It is a rapidly expanding area of research with huge potential in many sectors, ranging from healthcare to construction and electronics. The advance in nanotechnology leads to great scientific progress in the field of medical sciences. Applications of nanotechnology in oncology have produced an emerging field of study, nanooncology and with the ease they offer in design, nanoparticles have revolutionized the drug delivery sector [1,3]. Drug loaded nanoparticles can selectively target tumor cells, thereby keeping our healthy cells safe [2]. Above all, the small size of these nanoparticles makes it possible for them to cross the physiological barrier of our body.

Nanomedicine is the field in medicine that is applied in diagnosis to treatment of diseases and nanotechnology is used for developing diagnostic systems. Technology like electrochemiluminescence makes it possible to measure the substance at nanolevel [4]. For medical diagnosis, cellular imaging by nanoprobes like quantum dots, plasmonic nanoparticles, magnetic nanoparticles, nanotubes, nanowires, and multifunctional nanomaterials can be done [5-7]. The advantage of using nanoprobes is high volume/surface ratio, surface tailorability, multifunctionality, and intrinsic properties. Nanotechnology also helps in developing drugs, improving drug formulation and distribution in the body and also in targeting the specific therapeutic site. It can even be integrated into the classical medical procedure to help improve efficacy.

The rapid growth of robot technology expanded its applications in the health and medicinal science field which led to the development of nanobots. Nanobots are nanoscale machines that can be controlled to perform specific activities in the body. They have great flexibility, adaptability and accuracy. Nanobots consist of sensors and motors. In presence of any trouble causing intruders, they undergo conformational changes that catalyses the release of a substance to act against them. The concept of nanobots was first thought of by famous physicist Richard Feyman in 1959 and he talked about that being used as a cure for heart diseases in his talk “There’s Plenty of Room at the Bottom”. Robert Frietas then did a study on medical nanobots called respirocytes; resembling red blood cells. Advances in the fields of robotics, nano structuring, medicine, bioinformatics, and computers have led to the development of nanobot drug delivery systems. Some of the examples of nanobots are respirocyte nanobots, microbivore nanobots, surgical nanobots and cellular repair nanobots.

Among various elements that are used in nanobots, carbon due to its inert nature and strength becomes the best choice. These are used as an exterior coating of the nanobots to avoid attack by the host immune system [8]. Techniques like Scanning Electron Microscopy (SEM) and Atomic Force Microscopy (AFM) are used to establish a visual and haptic interface to learn about the molecular structure of nanobots. The main challenges in development of these nanobots are their fabrication and controls.

Robotic systems have dramatically extended the reach of human beings in sensing, interacting, manipulating and transforming the world around us [9]. Particularly, the confluence of diverse technologies has enabled a revolution in medical applications of robotic technologies towards improving healthcare. Medical robotic devices are designed for environments and operations relevant to the treatment and prevention of diseases. They require miniaturized parts and smart materials for complex and precise operations and mating with the human body. The rapid growth in medical robotics has been driven by a combination of technological advances in motors, control theory, materials, medical imaging and increased in surgeon/patient acceptance [10,11]. Before moving on to its further applications, let us first understand how exactly it is made, the parts involved and their functioning.

Parts and Design of Nanobots

One of the important applications of nanobots is to develop treatment to target the active site by minimising the impact on other unaffected parts of the body [12]. They are designed to detect and get to the affected part of the body and send feedback. nanobots can be made from almost any type of material and can have varied manufacturing processes. The two principle manufacturing conventions are top down or bottom up. The former process involves the extreme miniaturization of existing robotic devices while the latter describes a process of building starting at the atomic level and constructing any object one atom at a time.

Current technology has employed atomic force microscopes and scanning tunneling microscopes to arrange atoms. These can resolve specimens at the atomic level and be used to move atoms and molecules. The microscope precisely locates the particle that will be moved and then a higher electron force than is normally used for imaging is targeted on the particle. This is done in a vacuum and at very low temperatures approaching four degrees Kelvin to inhibit electron excitation and spatial uncertainty caused by temperature drift in the room and between the specimen and the probe when using a scanning probe microscope.

The important parts of a nanobot are sensors, motors, power supplies, molecular computers and manipulators.

Sensors: Different types of sensors are used in nanobots like mechanical, thermal, optical, magnetic, chemical and biological sensors [13]. Sensors detect the presence of the target molecules and indirectly know the amount of damage that exists from the change in the functional properties of nanobots. Biosensors use biological reactions to detect target analytes [14]. An example of biosensors is use of nano cantilevers as Nano Electro Mechanical System (NEMS). This system utilizes biological material that will be attached by itself to a coated cantilever, causing fundamental changes in mass or its surface tension [15]. They measure cell mass, biomolecules, nucleic acids and others, and detect specific molecules or even manipulate and place nanoparticles in a predefined arrangement [16-18]. Carbon Paste Electrodes (CPE) is also a type of nanosensor used for voltammetric measurements and even in coulometry, as a renewable surface for electron transfer reactions. They are easy to fabricate, can be miniaturised, have good electrical and mechanical resistance and come at a low cost [19].

Propulsion equipment: These are needed for movement of nanobots inside the body. Nanomotors are nanodevices with their own propulsion, obtaining the energy by chemical reactions of the medium, electricity, magnetic or acoustic fields [20,21]. Challenges faced to control movement of nanobots are viscosity and Brownian motion of the medium. To facilitate movement of nanobots, MRI devices were used. The speed and direction of nanobots were controlled from an external computer, decreasing the risk [22] and the MRI was used to get real-time feedback of the behavior of the nanobots.

In 2000, bio nanomotors were introduced. In this nano-electro-mechanical device was integrated with adenosine triphosphate synthase (ATPase). Another example is Janus motors which are made by nanoparticles that have two or more sides on their surface with different properties [23]. In this, there is a chemical reaction on one side of these nanoparticles, which produces the force for the movement of these motors. There are also nanomotors based on sphere based propulsion and osmotic propulsion. Gold-nano wired ultrasound-driven motors are being developed for their utilization as drug delivery devices in cancer cells. These motors are based on the nanoporous gold segment for increasing superficial area and hence the loading capacity of the drug.

Nanocomputers: They can be electronic, biochemical, organic or quantum and have the function of controlling or directing nanobots inside the body. Computers developed at a molecular level made up of DNA, having software coded with four letters of DNA nitrogenous bases can regulate gene expression. It can also detect the type of mRNA associated with specific genes that in case of being over expressed or its opposite induce the cancer. This allows diagnosing different types of cancer and counteracting the disease with the indicated drug [24].

The nanobot design consists of integrated nano electronics and components. Binding sites of different sensors have a different affinity for distinct molecule types. Sensors detect obstacles which require a new trajectory planning and their design depends on the environment and the task. A nanobot needs transducers capabilities and smart sensors directly related to specific biomedical application. It relies on chemical contact sensors to detect them. Different nanobot sensor based actions can be evaluated by this interaction capabilities [25]. By this, we can choose the kind of low-level control to maximize the information acquired for an effective real time performance. The nanobot kinematics can be predicted using state equations, positional constraints, inverse kinematics and dynamics, while some individual directional component performance can be simulated using control system models of transient and steady state response [26]. The capacity to design, build, and deploy large numbers of medical nanobots into the human body would make possible the rapid elimination of disease and the effective and relatively painless recovery from physical trauma.

Types of nanobots: Generally nanobots can be classified into two types i.e. organic also called bionanobot and inorganic nanobots.

Nanobots in drug delivery and therapeutics can also be classified according to the applications as described below:

Pharmacyte: It is a medical nanobot used to carry a given drug in the tanks. It is controlled using mechanical systems for sorting pumps. For full targeting accuracy, it has molecular markers or chemotactic sensors. Glucose and oxygen that are extracted from the local environments such as blood, intestinal fluid and cytosol are the on board power supply. Nanobots are removed after completing their tasks by centrifuge nanapheresis [29].

Diagnosis and Imaging nanobots: These nanobots have microchips projected to send electrical signals when the human molecules on the chips detect a disease. They can also be used to monitor the sugar level in the blood. Their production cost is and they can be easily manipulated [27].

Respirocyte: It is Artificial Oxygen Carrier nanobot. Its power is obtained by endogenous serum glucose. This artificial cell is able to give 236 times more oxygen to the tissues per unit volume than RBCs (Red blood cells). It is also used to administer acidity [28].

Microbivores: It is an oblate spheroidal device for nanomedical applications. The nanobot can continually consume power up to 200pW and this power is used to digest trapped microbes. It also has the ability to phagocyte approximately 80 times more efficiently than macrophages agents, in terms of volume/sec digested per unit volume of phagocytic agent [29].

Clottocytes: This nanobot has the ability for instant hemostasis. They are also called artificial mechanical platelets that are roughly spheroidal nucleus-free blood cells. Platelets join at a place of bleeding and are activated. Then they aid in stamping the blood vessel and stop the bleeding. They also deliver substances that help promote coagulation [28].

Chromallocyte: They replace entire chromosomes in individual cells thus reversing the effects of genetic disease and other accumulated damage to our genes, preventing aging. Usually inside a cell, first the repair machine sizes up the situation by examining the cell’s contents and activity, and then takes action by working along molecule-by-molecule and structure-by structure [29].

DNA nanobots: They are used to deliver the drug to the targeted cell so as to avoid side effects. Their aim is the design and fabrication of dynamic DNA nanostructures that do specific tasks via state changes done from the hybridization/denaturing of a single base to the hybridization/denaturing of entire strands. DNA nanobots use DNA origami where one long strand of DNA is folded to produce the desired structure with the help of smaller staple strands. This method is based on the folding of the large ssDNA (usually the 7.3 kilobase genome of the M13 bacteriophage) with an excess of smaller complementary strands called staple strands (typically 32 bases). These strands are complementary to at least two distinct segments of the long ss DNA. DNA nanobots are used as a targeted drug delivery system to improve treatment of diseases [64].

Applications of Nanobots

Owing to their small size, the nanobots have unique properties that do not exist in other larger counterparts, including increased surface area, charge, reactivity, and other physicochemical properties, all of which may affect how these nanomaterials interact with biological entities. The potential applications of nanobots are:

For Drug delivery: Nanobots having the ability of controlled navigation deliver drugs to the target or affected areas, hence treating many diseases. They can even penetrate into tissues [30]. These nanobots are usually propelled and/or guided by endogenous or exogenous stimuli towards the area of interest [31]. Wire-shaped magnetoelectric nanobots designed and fabricated can be precisely steered toward a targeted location by means of wireless magnetic fields and can perform on-demand magneto electrically assisted drug release to cells [32]. Ultrasound-powered nanowire motors has been developed based on a nanoporous gold segment and showed that the nanoporous gold structure can facilitate the Near-Infrared (NIR)-light-controlled drug release through photothermal effects [33]. A DNA nanobot was made which was capable of delivering molecular payloads to cells and was controlled by an aptamer-encoded logic gate, enabling the robot to respond to a wide array of signals such as cell surface markers [34]. Gold nanowires conjugated with a cytokine such as tumor necrosis factor-alpha can be transported along any prescribed trajectory or orientation using electrophoretic and dielectro-phoretic forces to a specific location with subcellular resolution, promoting the development of controlling signaling events on the single-cell level [35].