Ajnn v11 Id1067
Ajnn v11 Id1067
Ajnn v11 Id1067
Review Article
Introduction
Nanotechnology makes it possible to manipulate matter at nanoprobes like quantum dots, plasmonic nanoparticles, mag-
the atomic and molecular scale to design materials with remark- netic nanoparticles, nanotubes, nanowires, and multifunctional
ably diverse and advanced properties. It is a rapidly expanding nanomaterials can be done [5-7]. The advantage of using nano-
area of research with huge potential in many sectors, ranging probes is high volume/surface ratio, surface tailorability, mul-
from healthcare to construction and electronics. The advance in tifunctionality, and intrinsic properties. Nanotechnology also
nanotechnology leads to great scientific progress in the field of helps in developing drugs, improving drug formulation and dis-
medical sciences. Applications of nanotechnology in oncology tribution in the body and also in targeting the specific thera-
have produced an emerging field of study, nanooncology and peutic site. It can even be integrated into the classical medical
with the ease they offer in design, nanoparticles have revolu- procedure to help improve efficacy.
tionized the drug delivery sector [1,3]. Drug loaded nanopar-
The rapid growth of robot technology expanded its applica-
ticles can selectively target tumor cells, thereby keeping our
tions in the health and medicinal science field which led to the
healthy cells safe [2]. Above all, the small size of these nanopar-
development of nanobots. Nanobots are nanoscale machines
ticles makes it possible for them to cross the physiological bar-
that can be controlled to perform specific activities in the body.
rier of our body.
They have great flexibility, adaptability and accuracy. Nanobots
Nanomedicine is the field in medicine that is applied in di- consist of sensors and motors. In presence of any trouble caus-
agnosis to treatment of diseases and nanotechnology is used ing intruders, they undergo conformational changes that cataly-
for developing diagnostic systems. Technology like electroche- ses the release of a substance to act against them. The concept
miluminescence makes it possible to measure the substance of nanobots was first thought of by famous physicist Richard
at nanolevel [4]. For medical diagnosis, cellular imaging by Feyman in 1959 and he talked about that being used as a cure
Journal of Nanomedicine & Nanotechnology Citation: Parida S, Bari AR. Nanobots for Medicinal Applications. Austin J Nanomed
Volume 11, Issue 1 (2023) Nanotechnol. 2023; 11(1): 1067.
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Anil Ramdas Bari © All rights are reserved
Anil Ramdas Bari Austin Publishing Group
for heart diseases in his talk “There’s Plenty of Room at the from the change in the functional properties of nanobots. Bio-
Bottom”. Robert Frietas then did a study on medical nanobots sensors use biological reactions to detect target analytes [14].
called respirocytes; resembling red blood cells. Advances in the An example of biosensors is use of nano cantilevers as Nano
fields of robotics, nano structuring, medicine, bioinformatics, Electro Mechanical System (NEMS). This system utilizes biologi-
and computers have led to the development of nanobot drug cal material that will be attached by itself to a coated cantile-
delivery systems. Some of the examples of nanobots are respi- ver, causing fundamental changes in mass or its surface tension
rocyte nanobots, microbivore nanobots, surgical nanobots and [15]. They measure cell mass, biomolecules, nucleic acids and
cellular repair nanobots. others, and detect specific molecules or even manipulate and
place nanoparticles in a predefined arrangement [16-18]. Car-
Among various elements that are used in nanobots, carbon bon Paste Electrodes (CPE) is also a type of nanosensor used
due to its inert nature and strength becomes the best choice. for voltammetric measurements and even in coulometry, as a
These are used as an exterior coating of the nanobots to avoid renewable surface for electron transfer reactions. They are easy
attack by the host immune system [8]. Techniques like Scanning to fabricate, can be miniaturised, have good electrical and me-
Electron Microscopy (SEM) and Atomic Force Microscopy (AFM) chanical resistance and come at a low cost [19].
are used to establish a visual and haptic interface to learn about
the molecular structure of nanobots. The main challenges in de- Propulsion equipment: These are needed for movement of
velopment of these nanobots are their fabrication and controls. nanobots inside the body. Nanomotors are nanodevices with
their own propulsion, obtaining the energy by chemical reac-
Robotic systems have dramatically extended the reach of tions of the medium, electricity, magnetic or acoustic fields
human beings in sensing, interacting, manipulating and trans- [20,21]. Challenges faced to control movement of nanobots
forming the world around us [9]. Particularly, the confluence of are viscosity and Brownian motion of the medium. To facilitate
diverse technologies has enabled a revolution in medical appli- movement of nanobots, MRI devices were used. The speed and
cations of robotic technologies towards improving healthcare. direction of nanobots were controlled from an external com-
Medical robotic devices are designed for environments and op- puter, decreasing the risk [22] and the MRI was used to get real-
erations relevant to the treatment and prevention of diseases. time feedback of the behavior of the nanobots.
They require miniaturized parts and smart materials for com-
plex and precise operations and mating with the human body. In 2000, bio nanomotors were introduced. In this nano-
The rapid growth in medical robotics has been driven by a com- electro-mechanical device was integrated with adenosine tri-
bination of technological advances in motors, control theory, phosphate synthase (ATPase). Another example is Janus motors
materials, medical imaging and increased in surgeon/patient which are made by nanoparticles that have two or more sides
acceptance [10,11]. Before moving on to its further applica- on their surface with different properties [23]. In this, there is
tions, let us first understand how exactly it is made, the parts a chemical reaction on one side of these nanoparticles, which
involved and their functioning. produces the force for the movement of these motors. There
are also nanomotors based on sphere based propulsion and
Parts and Design of Nanobots osmotic propulsion. Gold-nano wired ultrasound-driven motors
One of the important applications of nanobots is to develop are being developed for their utilization as drug delivery devices
treatment to target the active site by minimising the impact on in cancer cells. These motors are based on the nanoporous gold
other unaffected parts of the body [12]. They are designed to segment for increasing superficial area and hence the loading
detect and get to the affected part of the body and send feed- capacity of the drug.
back. nanobots can be made from almost any type of material Nanocomputers: They can be electronic, biochemical, or-
and can have varied manufacturing processes. The two princi- ganic or quantum and have the function of controlling or di-
ple manufacturing conventions are top down or bottom up. The recting nanobots inside the body. Computers developed at a
former process involves the extreme miniaturization of existing molecular level made up of DNA, having software coded with
robotic devices while the latter describes a process of building four letters of DNA nitrogenous bases can regulate gene expres-
starting at the atomic level and constructing any object one sion. It can also detect the type of mRNA associated with spe-
atom at a time. cific genes that in case of being over expressed or its opposite
Current technology has employed atomic force microscopes induce the cancer. This allows diagnosing different types of can-
and scanning tunneling microscopes to arrange atoms. These cer and counteracting the disease with the indicated drug [24].
can resolve specimens at the atomic level and be used to move The nanobot design consists of integrated nano electronics
atoms and molecules. The microscope precisely locates the par- and components. Binding sites of different sensors have a dif-
ticle that will be moved and then a higher electron force than ferent affinity for distinct molecule types. Sensors detect ob-
is normally used for imaging is targeted on the particle. This is stacles which require a new trajectory planning and their design
done in a vacuum and at very low temperatures approaching depends on the environment and the task. A nanobot needs
four degrees Kelvin to inhibit electron excitation and spatial un- transducers capabilities and smart sensors directly related to
certainty caused by temperature drift in the room and between specific biomedical application. It relies on chemical contact
the specimen and the probe when using a scanning probe mi- sensors to detect them. Different nanobot sensor based actions
croscope. can be evaluated by this interaction capabilities [25]. By this,
The important parts of a nanobot are sensors, motors, pow- we can choose the kind of low-level control to maximize the
er supplies, molecular computers and manipulators. information acquired for an effective real time performance.
The nanobot kinematics can be predicted using state equations,
Sensors: Different types of sensors are used in nanobots like positional constraints, inverse kinematics and dynamics, while
mechanical, thermal, optical, magnetic, chemical and biologi- some individual directional component performance can be
cal sensors [13]. Sensors detect the presence of the target mol- simulated using control system models of transient and steady
ecules and indirectly know the amount of damage that exists state response [26]. The capacity to design, build, and deploy
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large numbers of medical nanobots into the human body would Applications of Nanobots
make possible the rapid elimination of disease and the effective
and relatively painless recovery from physical trauma. Owing to their small size, the nanobots have unique prop-
erties that do not exist in other larger counterparts, including
Types of nanobots: Generally nanobots can be classified increased surface area, charge, reactivity, and other physico-
into two types i.e. organic also called bionanobot and inorganic chemical properties, all of which may affect how these nano-
nanobots. materials interact with biological entities. The potential applica-
tions of nanobots are:
Nanobots in drug delivery and therapeutics can also be clas-
sified according to the applications as described below: For Drug delivery: Nanobots having the ability of controlled
navigation deliver drugs to the target or affected areas, hence
Pharmacyte: It is a medical nanobot used to carry a given treating many diseases. They can even penetrate into tissues
drug in the tanks. It is controlled using mechanical systems [30]. These nanobots are usually propelled and/or guided by
for sorting pumps. For full targeting accuracy, it has molecular endogenous or exogenous stimuli towards the area of interest
markers or chemotactic sensors. Glucose and oxygen that are [31]. Wire-shaped magnetoelectric nanobots designed and fab-
extracted from the local environments such as blood, intestinal ricated can be precisely steered toward a targeted location by
fluid and cytosol are the on board power supply. Nanobots are means of wireless magnetic fields and can perform on-demand
removed after completing their tasks by centrifuge nanapher- magneto electrically assisted drug release to cells [32]. Ultra-
esis [29]. sound-powered nanowire motors has been developed based
Diagnosis and Imaging nanobots: These nanobots have mi- on a nanoporous gold segment and showed that the nanopo-
crochips projected to send electrical signals when the human rous gold structure can facilitate the Near-Infrared (NIR)-light-
molecules on the chips detect a disease. They can also be used controlled drug release through photothermal effects [33]. A
to monitor the sugar level in the blood. Their production cost is DNA nanobot was made which was capable of delivering mo-
and they can be easily manipulated [27]. lecular payloads to cells and was controlled by an aptamer-en-
coded logic gate, enabling the robot to respond to a wide array
Respirocyte: It is Artificial Oxygen Carrier nanobot. Its power of signals such as cell surface markers [34]. Gold nanowires con-
is obtained by endogenous serum glucose. This artificial cell is jugated with a cytokine such as tumor necrosis factor-alpha can
able to give 236 times more oxygen to the tissues per unit vol-
ume than RBCs (Red blood cells). It is also used to administer
acidity [28].
Microbivores: It is an oblate spheroidal device for nanomed-
ical 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 di-
gested per unit volume of phagocytic agent [29].
Figure 1: Nanobot (Courtesy-https://doctorinprogress.
Clottocytes: This nanobot has the ability for instant hemo- com/2019/09/01/nanobots-in-medicine/?locale=en).
stasis. 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 sub-
stances that help promote coagulation [28].
Chromallocyte: They replace entire chromosomes in individ-
ual 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 ac- Figure 2: Medical nanobot (Courtesy-https://www.cnet.com/
tion by working along molecule-by-molecule and structure-by news/nanobots-can-now-swarm-like-fish-to-perform-complex-
structure [29]. medical-tasks/).
DNA nanobots: They are used to deliver the drug to the tar-
geted 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/denatur-
ing 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 Figure 3: Nanobots with the size as small as bacteria (Credits-
ss DNA. DNA nanobots are used as a targeted drug delivery sys- https://www.cnet.com/news/nanobots-can-now-swarm-like-fish-
tem to improve treatment of diseases [64]. to-perform-complex-medical-tasks/).
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Table 1: Types of nanobots. Nanorobots can also be used for routine cleaning, cosmetics
Types Manufactured using Toxicity and teeth whitening, hypersensitivity, and orthodontics [100].
There are many benefits of neurosurgery including improved
Organic Viruses and bacteria DNA cells Less toxic
detection of pathology, minimally invasive intracranial monitor-
Inorganic Diamond structures, synthesized proteins More toxic ing, and pharmaceutical delivery. Intravascular nanorobots are
Table 2: Recent Nanobots. designed with the capability to detect aneurysm formation by
Field of medicine Nanorobotic application References
detecting increased levels of nitric oxide synthase protein within
the affected blood vessel. These nanorobots wirelessly commu-
Magnetotactic bacteria is used to transport
Microbiology [98] nicate information about pertinent vascular changes [101]. DNA
and navigate nanobots
robots can be programmed to transport payloads and present
Ultrasound-powered nanobots swim them specifically in tumors. The outer side is functionalized
Hematology through blood and remove harmful bacte- [99] with a DNA aptamer that binds nucleolin and the inside with
ria, nanobots is used for haemostasis blood coagulation protease thrombin. The nucleolin-targeting
Nanobot penetrating dentinal tubules aptamer acts as a targeting domain and a molecular trigger for
Dentistry is used for administration of targeted [100] the mechanical opening of the DNA nanorobot. The thrombin
analgesic inside is thus exposed and activates coagulation at the tumor
Nanobot is used for the monitoring of site and that induces intravascular thrombosis resulting in tu-
Neurosurgery intracranial aneurysm development and [101] mor necrosis and inhibition of tumor growth [102,103].
progression
Nanobots have diverse applications in medicinal chemistry
DNA nanobots can do precise drug delivery like molecular machines [73-75], self-propelled nanomotors
Oncology [102,103]
for cancer therapy.
[76-78], and DNA nanorobotics [79-81]. Nanobots are also be-
Screening nanobot can circulate and moni- ing used in the current world for transporting biological sub-
tor for detection of neoplasia stances (e.g., ions [82], molecules [83], drugs [84]), in vivo treat-
ing diseases (e.g., cancers [85], renal damage [81]), handling
The wide applications of nanobots promote the development different types of biological samples (e.g., single cells [86,87],
of biomedical technology and human healthcare. organelles [88], exosomes [89], single molecules on cells [90])
and also characterizing biomaterials for regulating cellular be-
Recent Nanobots
haviors [91-93]. However, the challenges that are faced put a
In 2012, Diagnostic nanosensor was invented for diagnosis in limit to their use.
medicine based on metallic semiconductors and magnetic na-
Challenges for Handling of Nanobots
noislands. The surface of these nanoparticles can be modified
to achieve interaction with the molecule of interest or recognize With the advancements in the fields of nanotechnology, ro-
a specific substrate surface as a cell membrane. So these can be botics, biomedicine, and electromechanical science, nanobots
used for the detection of pathogens or toxins inside the body have made considerable improvements. nanobots possess
[65]. In 2016, a nanobot was developed to create more efficient unique and multivalent functionalities that include fast motion
cancer markers and to reduce side effects from cancer treat- in complex biological media, large cargo-towing force for direc-
ment. This robot is composed of a loading component, a power tional and long-distance transport, easy surface functionaliza-
component and a connecting component. The nanobot releas- tion for precise capture and isolation of target subjects, and
es a labeling reagent at the specific point where there is a tu- excellent biocompatibility for in vivo operation. To accommo-
mor. The motor is propelled by ATP [66]. Nanobots called Nano date the growing demands of nanobots, we need to address the
Bee that destroy brain cancer cells were simulated in 2016 [67]. challenges associated with them.
These can detect cancer cells and destroy them. They emit an
acoustic signal when the tumor is detected. Though nanobots have unrivalled advantages due to their
size, they also face some challenges. When the dimensions are
Nanorobots containing therapeutic compounds integrated reduced to nano scale, the nature of certain physical laws is al-
into magnetotactic bacteria would be the bacterial cell com- tered due to changes in the surface area-to-volume ratio and
ponent. Magnetotactic cocci are used for intravascular func- surface area. Perimeter-related forces tend to predominate.
tions and travel in consistent and predictable patterns fol- The behavior of nanobots is also relatively susceptible to tem-
lowing established geomagnetic lines. These robots function perature, humidity, and fluids [46,47].
in and navigate through blood vessels. The magnetosomes in
magnetotactic bacteria are guided by magnetic fields [98]. Tiny One of the challenges faced by nanobots is multi-functional-
ultrasound-powered robots can offer a safe and efficient way to ity. Due to their size, existing nanobots have a single function,
detoxify and decontaminate biological fluids. These nanobots and it is challenging to integrate multiple functions into one
are built by coating gold nanowires with a hybrid of platelet and robot. It is important for smart nanobots to incorporate signal
red blood cell membranes. The platelets bind pathogens and perception, acquisition, processing and transmission in them.
red blood cells absorb and neutralize the toxins produced by To grasp the real-time position of the robot and for prevent-
these bacteria. The gold coating of the nanorobots responds to ing the nanobot from losing contact with external controls,
ultrasound, which gives them the ability to swim around rap- the feedback mechanism needs to be improved. The operation
idly without chemical fuel and speed up detoxification [99]. and intelligence of nanobots rely primarily on their materials
Nanorobots can be used in almost every aspect of dentistry. and surface properties. Biomedical nanobots are designed for
These are administered orally and they enter the gingival sul- environments like unanticipated biological events, changing
cus, and travel through the dental tubules to reach the pulp. physiological conditions, and soft tissues. Diverse smart materi-
These nanorobots allow activation of analgesic activity in highly als, such as biological materials, responsive materials, or soft
specific areas in proximity to where the treatment will be done. materials are expected to provide the necessary actuation and
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multi-functionality and avoid irreversible malfunctions in com- operations. For locomotion of nanobots in aqueous media,
plex physiologically-relevant body systems. Synthetic nanoma- many chemical fuels and external stimuli have been explored
chines coupled with natural biological materials can minimize [51]. nanobots have already demonstrated great performance
undesired immune evasion and biofouling effects experienced in viscous biological fluids such as gastric fluid or whole blood
in complex biological fluids, leading to enhanced mobility and [55-57]. Enzyme-functionalized nanomotors can be powered by
lifetime in them [60]. For designing configurable nanobots for bodily fluid constituents, such as blood glucose or urea [52-54].
adaptive operation under rapidly changing conditions, we need The power and stability of these motors need more improve-
responsive materials. Nanobots need to be soft and deformable ments for practically implementing them. Magnetic and acous-
to ensure maneuverability and mechanical compliance to hu- tic nanomotors can provide fuel-free and on-demand speed
man body and tissues [61,62]. They should be made of transient regulation for surgery at nanoscale but they might hinder au-
biodegradable materials that disappear upon completing their tonomous therapeutic interventions.
tasks [63]. For large-scale, high-quality, and cost-efficient fabri-
cation of biomedical nanobots, new synthesis and cutting-edge For working in human tissues and organs nanobots have
fabrication methods should be explored. an advantage of size. Nanoscale magnetic propellers display a
significant advantage for propulsion in viscoelastic hyaluronan
Biomedical nanobots need to cooperate with one another gels as they are of the same size range as the openings in the
for performing tasks like effective delivery of large therapeutic gel’s mesh, compared to the impeded motion of larger propel-
payloads or large-scale detoxification processes, which are not lers [58]. So, nanobots can achieve efficient motion in tissues by
possible using a single robot. Mimicking the natural swarm in- their nanoscale size and optimized design. They can overcome
telligence communication and synchronized coordination, from cellular barriers and internalize into cells [59].
one to many, is a challenging task. It is highly important for
enhancing their precision treatment capability. With the con- Current nanobots have drawbacks in energy conversion
ventional optical microscopy techniques, it is difficult for high- mechanisms, control methods and fabrication technologies.
resolution simultaneous localization and mapping of nanobots The magnetic drive needs an external magnetic field, the elec-
in the human body. Future biomedical nanobots will require tric field drive requires external electrodes, and the light drive
their coupling with modern imaging systems and feedback con- needs light to penetrate the tissue. Most existing methods con-
trol systems for arbitrary four-dimensional navigation of many- trol the nanobots to move in the 2D plane and lack movement
nanobot systems. control in the third dimension. Many nanobots are driven by
corrosive chemical fuels which creates problems when used in
Another challenge is problems faced by nanobots in clinical vivo. For better diagnosis and treatment, the nanobot should
applications and crossing the gap between scientific research load more drugs. For commercialization of nanobots, the manu-
results and the market demand. Though there are many models facturing costs should be reduced. Instead of expensive met-
of nanobots out there, they are rarely used. For in vivo appli- als, low-priced metals need to be used [95]. and water can be
cations things like biocompatibility, reliability and biodegrad- used instead of other chemical reagents to drive nanobots [96].
ability need to be considered. The nanobots entering the living Bio-syncretic robots have both living components and nonliving
body should have the ability to cross barriers like blood vessels components [97]. Some living microorganisms can be directly
and tissues. They also should not be rejected by the body when used to assemble nanobots since they have the capability to
they enter, should be harmless to normal tissues, and should act as sensing or driving elements for the robots. Biomateri-
have no side effects. The material of the robot should be biode- als have higher sensitivity than inorganic materials. But when
gradable or it should be equipped with an integrated recycling these nanobots are used in the air, the long-term survival of
mechanism. The nanoparticles involved in certain medical de- living biological components is a challenge. So, they must be
vices interact with both the outer environment and the human supplied with nutrients and gases and should be operated in a
body. The risks humans have with it are in the adsorption of controlled-humidity environment. This is why innovative mate-
biomolecules and oxidative stress, causing DNA damage. The rials with better environmental adaptability are needed.
inability to control the movement of the nanoparticles through-
out the body creates a risk that they can reach undesirable Discussion
locations and lead to side effects. One of the main character- Over the past few years, a number of theoretical and experi-
istics of nanoparticles is that they can cross biological barriers mental studies have led to the development of various nano-
[48]. This can be a disadvantage since the unnecessary cross bots that are propelled by different mechanisms. Currently, the
of barriers may be a trigger for some inflammatory reactions. clinical translation of nanobots is very limited because of the
The ethical aspects involved in the diagnosis of diseases should challenges faced by them. So, nanorobotics has been a reality to
also be evaluated. When patients are known to be prone to a some extent for medicinal chemistry applications but we have
disease through gene analysis, things like who will possess such a room for its advancement for better applications. The present
information, how fundamental rights can be protected, how nanobots mainly act as drug carriers and their movements rely
responsible use of nanomedicine can be promoted should be on the blood flow and once the drug inside is released at the
considered [48]. The risk nanobots pose for the environment is target site, the nanobots are cleared by our immune system. Re-
much more complex by the large number of interactions that using nanobots and communication and coordination between
are involved [49]. nanobots inside the body is needed to expand the applications.
For getting the full potential of the nanobots, great efforts Pathological changes in the cell, alters its physical properties.
and innovations are needed. Future nanobots are expected to So, applying physical property detection based on nano ma-
mimic the natural intelligence of their biological counterparts nipulators to drug efficacy prediction will increase their preci-
with great mobility, adaptable and sustainable operation, pre- sion. Automated hybrid nanorobotic systems integrating differ-
cise control, self-evolving and self-replicating capabilities. We ent types of nano manipulators can combine their advantages
need good energy sources for prolonged, biocompatible in vivo which will benefit handling biological samples of patients with
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Acknowledgements
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Virtual Internship with Science Leaders program for giving me 151.
the opportunity to work under an eminent scientist and uti-
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heartfelt gratitude to the supervisor Dr. Anil Ramdas Bari for applications of nanosensors and nanobiosensors in medicine
guiding the way throughout and acting as constant support. and environmental analysis. International Journal of Nanotech-
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Competing Interests
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The authors hereby declare that there is no competing inter- motors in diagnostics. Adv Drug Deliv Rev. 2015; 95: 104–116.
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