Materials Today: Proceedings xxx (xxxx) xxx

Contents lists available at ScienceDirect

Materials Today: Proceedings

journal homepage: www.elsevier.com/locate/matpr

A futuristic insight into a ‘‘nano-doctor”: A clinical review on medical

diagnosis and devices using nanotechnology
Ojo P. Bodunde a, Omolayo M. Ikumapayi b,e,⇑, Esther T. Akinlabi c, Bankole I. Oladapo d,
Adeyinka O.M. Adeoye e, Samuel O. Fatoba b
a
Department of Mechanical and Automation Engineering, Chinese University of Hong Kong, Shatin, NT, People’s Republic of China
b
Department of Mechanical Engineering Science, University of Johannesburg, Auckland Park Kingsway Campus, Johannesburg 2006, South Africa
c
Pan African University for Life and Earth Sciences Institute (PAULESI), Ibadan, Nigeria
d
School of Engineering and Sustainable Development, De Montfort University, Leicester, UK
e
Department of Mechanical and Mechatronics Engineering, Afe Babalola University, Ado Ekiti, Nigeria

a r t i c l e i n f o a b s t r a c t

Article history: Surgical sciences are very important for human existence and survival. Surgery, however, is not a 100
Received 20 August 2020 percent success probability operation. In fact, some decades ago, surgical operations are generally
Accepted 10 November 2020 regarded as a 50 percent probable risk operation. This review highlights the invention of nanotechnology
Available online xxxx
to eliminate piercing type of surgery and invent a step by step approach that could bring about the devel-
opment of a nano-doctor who can operate by minimal invasion and much less invasion. The coming to
Keywords: limelight of nanomedicine as a child’s play of combining nanotechnology with pure sciences such as biol-
Nanotechnology
ogy and chemistry were discussed. The possibility of developing a nano-doctor was discussed based on an
Nanomedicine
Nanosurgery
integration with 4th industrial revolution (4IR) technologies and the pros and cons of inventing and
Nano-doctor adopting a nano-doctor were explained as a documented review which could serve as a baseline knowl-
Minimally invasive technologies edge for its realization. Few challenges such as human body complexity, safety, ethical, regulatory, man-
ufacturing and characterization concerns were also identified and cogently discussed as some upcoming
issues. The possible integration of modern 4IR tools such as artificial intelligence (AI), robotics, machine
learning, ZigBee technology, and internet of things (IoTs) were briefly touched. This review established
the possibility of inventing a nano-doctor for surgical operation which will in turn be of great benefits
to human health.
Ó 2020 Elsevier Ltd. All rights reserved.
Selection and peer-review under responsibility of the scientific committee of the International Confer-
ence on Materials, Processing & Characterization.

1. Introduction mental used. The desirability of nanomedicine’s applications owes

Surgery and surgical related medicines are traditionally carried
out using piercing objects such as surgery knives, scissors etc. The
major purpose of carrying out this piercing operation is to see the
internal organ or tissue that is/are malfunctioning. Usually, it takes
a close relative of the patient to sign as the surgical operation is 50
percent success probability. Nanotechnology and health are two
words that seem not to belong in the same school of thoughts
and ideas. This is not the case, as nanotechnology has recently
become the pillar behind some of the most significant inventions
in the medical treatments in the modern day which is now funda-
⇑ Corresponding author.
E-mail address: ikumapayi.omolayo@gmail.com (O.M. Ikumapayi).
to the fact that there are unbeatable attributes of 3-D develops
with various components in nanoscale [1]. Human body is an
extremely complex structure of interacting cells, tissues, organs
and/or systems. Therefore, it is imperative to deploy appropriate
technology to understand the human body and develop novel gad-
gets to repair it, should damage arises. Due to the complexity of
human body and its internal structure, nanomedicine product
must be carefully design with engineering standards, a well-
controlled physicochemical, manufacturing procedures and an
highly replicate scale-up to meet up with standardized products
with consistent physicochemical properties, pharmacological pro-
file as well as biological characteristics [2]. It must be noted that
the safety and the regulatory issues in the field of nanomedicine
must be well guided and guarded as compared to conventional

https://doi.org/10.1016/j.matpr.2020.11.232
2214-7853/Ó 2020 Elsevier Ltd. All rights reserved.
Selection and peer-review under responsibility of the scientific committee of the International Conference on Materials, Processing & Characterization.

Please cite this article as: O.P. Bodunde, O.M. Ikumapayi, E.T. Akinlabi et al., A futuristic insight into a ‘‘nano-doctor”: A clinical review on medical diagnosis
and devices using nanotechnology, Materials Today: Proceedings, https://doi.org/10.1016/j.matpr.2020.11.232
O.P. Bodunde, O.M. Ikumapayi, E.T. Akinlabi et al. Materials Today: Proceedings xxx (xxxx) xxx

medicines. This review details the prospects, challenges and merits

in the past, present and future that has been occurred during the
phase changes of nanotechnology as well as commercialization of
nanomedicine products and a well analysed solutions has been
proposed to speed-up the growth of this earth-shaking and signif-
icant field. Nanoscience involves research, technology, and innova-
tions at nanoscale. A nanoscale ranges from 1 nm to 100 nm and by
definition is the one-billionth of a metre (1 billionth of 1 m) or one-
millionth of a millimeter (1 millionth of 1 mm). Fig. 1 illustrates
diagrammatically the measurements at nanoscale and objects that
are measured at nanoscale, also compares them with other scales.
As tiny as the human hair, its metrics cannot be classified as nanos-
cale because it size is about 80,000 nm [3].
It aims at monitoring, controlling, repairing, construction and
defence of human biological system from the perspective of molec-
ular level. It uses engineered devices and nanostructures to benefit
medical well-being. As shown is Fig. 2, nanomedicine covers
branches of science with an application of nanotechnology. Fig. 2. Nanomedicine/surgery as an interdisciplinary field of science and
The invention of Nanomedicine has been probed by the nanotechnology.
researched conducted by some group of best doctors and some
remarkable findings have been documented. The findings had
posed several questions to the doctors, e.g. What if we could stop room at the bottom: An Invitation to Enter a New Field of Physics”
treating a genetic disease, and simply ‘‘turning off” the offending [7]. Nonetheless Albert Hibbs and his idea of ‘‘swallowing the sur-
gene? That is a typical question and hence a great potential of nan- geon” were credited with illuminating the medical field with nan-
otechnology. It was revealed that DNA nanoparticle that are very otechnology. In this situation, the diagnosis could be made by tiny
small in size were able to pass through the cell walls that were robots which examine the internal structures of the body and thus
developed using the knowledge garnered from nanotechnology recognize any problems that have been identified and then repair
and the study further revealed that they are capable of enable cells them [8].
to create their own therapeutic substances, to replace defective
genes as well as ‘‘turn off” the problem genes. This particular tech-
nology has gone beyond theoretical practices [4]. Since the debut 2. Historical background
entrance of nanotechnology in medical devices, reports show that
several industries have gone into the business of nano-coating that As mentioned earlier, the concept of nanotechnology was not
make full-size devices in order to prolong their expectant life e.g. clear until late 1950s when a physicist named Richard Feynman
pacemakers or artificial hips, more harmonious and synergetic delivered a broad-minded lecture during a section at the American
with the human body. They can possess the following attributes: Physical Society at CALTECH, USA entitled ‘‘There’s Plenty of Room
less rejection, less irritation, more healthy results as well as less at the Bottom”. His suggestion was based on the possibility of mak-
infection [5]. For nanomedicine to be possible, certain materials ing machines at nanoscale. Later the process of nanotechnology
must be explored. Such nanomaterials are easily obtainable, rang- was described and named in early 1970s by Professor Norio Tani-
ing from magnetotactic bacteria using iron oxide nanoparticles in guchi of the Tokyo Science University, Japan.
reaction to magnetic fields to peculiar butterfly wing colours The word ‘‘nanotechnology” could not be used aftermath of his
resulting from light interactions with complex nano-architectures lecture not until 1974 by Norio Tanaguchi, he then gave definition
and not from colour or pigment absorption [6]. Recently, Richard for nanotechnology as being able to manipulate a single nanoscale
Feynman conceived a conceptual idea requiring nanoscale-level object [9]. Ever since this debut entrance, nanotechnology has
manipulation of matter, propelling the lecture given in a 1959 metamorphosed into so many fields including the field of medicine
American Physical Society program entitled ‘‘There is plenty of and surgery. Hence, it is called nanomedicine/nanosurgery [10].

Fig. 1. Measurements at nanoscale [3].

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O.P. Bodunde, O.M. Ikumapayi, E.T. Akinlabi et al. Materials Today: Proceedings xxx (xxxx) xxx

Fig. 3. Increasing trend of nanotechnology applications.

The increasing trend of nanotechnology applications is presented
in Fig. 3.
2.1. 1980’s
The innovation made about scanning tunneling at IBM and the
atomic force microscope in the early to mid-1980s brought about
the imaging of atomic-resolution surfaces [11,12]. The imagery
later led to the placement of atoms in certain positions and marks
the beginning of nanotechnology realization [13]. Also, in the early
1980s, at the Massachusetts Institute of Technology, a group devel-
oped a promising alternative vision designed for nanotechnology
that centred significantly on the biological devices which is more
of protein design and this approach was bottom-up nanotechnol-
ogy [14]. This vision came into being as a result of the speech deliv-
ered by Feynman’s 1959 and this lead to the birth of the first book
on nanotechnology entitled, ‘‘Engines of Creation: The Coming Era of
Nanotechnology” which was officially published in 1986 and also
the creation of the first organization – the Foresight Institute in
the same year, specially assigned to see to the development of nan-
otechnology [15]. Earlier year before this development, Kroto and
his colleagues, in 1985 discovered the 60 Carbon atom structure
from Rice University which also has remarkable contribution to
the emerging of nanotechnology [16].
2.2. 1990’s
However, In the 1990s, as the field of nanotechnology continu-
ally spreading, leading to the introduction of the first international
journal devoted for subject related to nanotechnology and this was
entitled ‘‘Nanotechnology,” published by IOP Publishing in the Uni-
ted Kingdom and in this journal the first time the word
‘‘Nanomedicine” was coined out. The scientific advancements in
the field continued to grow, therefore emergence of nanoparticles
i.e. the discovery of the carbon nanotube, the discovery of the poly-
electrolyte complex micelle [17,18].
to new development especially in the field of medicine. Alliance
for Nanotechnology in cancer was launched in 2004 by the United
States National Institute of Health (NIH) in collaboration with
National Cancer Institute (NCI). The multipurpose institutional
centre was established for training, research, collaboration as well
as characterization. The established centres for cancer nanotech-
nology excellence across the globe had been foreseen to lose fund-
ing in 2020 and this was attributed to lack of interest in the field.
Nonetheless, a transition has also been previsioning for nanotech-
nology to change from emerging field to a more established field
[18,19].
3. Application of nanotechnology in medicine
Nanotechnology finds application in day to day activities as
depicted in Fig. 4, is a statement that cannot be overemphasised.
Nanotechnology encapsulates the production and the materials
usage in nanoscale dimensions across different fields of human
endeavour. Due to nanoscale dimension of nanoparticle, the high
surface-to-volume ratios and specific properties were always
established. Nanotechnology has a new and emerging area, its
applications amongst others involve the development of innova-
tive methods, formulation of new chemical and materials, fabrica-
tion of new products as well as substitution of current generation
of equipment with the most recent and sophisticated and
improved performance equipment that will eventually lead to
lower materials and energy consumption, reduce environmental
risk and proffer environmental remediation [20].

2.3. Modern history till date

It is apparent that the enthusiasm and confidence of nanotech-

nology would soon penetrate the political globe, and this led to the
creation in 1998 of the Interagency Working Group on Nanotech-
nology, which launched the United States National Nanotechnol-
ogy Initiative in 2000 [National Research Council, 2002]. In the
same vein, the National Nanotechnology Institute of Canada was
founded in 2001. These initiates will surge money that will lead Fig. 4. Nanotechnology as applied to day to day activities [20].

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O.P. Bodunde, O.M. Ikumapayi, E.T. Akinlabi et al. Materials Today: Proceedings xxx (xxxx) xxx

3.1. Diagnosis nanoparticles could be modified in order to absorb near infrared

It was revealed that nanomaterials possessed inherent physico-
chemical properties due to their sizes as well as compositions and
these attributes engineered the applications in medical and biolog-
ical context. One of the areas within the remit of nanomedicine in
which there has been intense investigation especially in recent
years was nanoparticle research [21]. ‘‘Nanoparticle” is a coverage
term for several shapes and sizes of nanovector structures as
depicted in Fig. 5 and these nanoparticles possessed the potency
to revolutionise the manner at which diseases like cancer are pre-
sently diagnosed and treated. It is essential to note that, nanopar-
ticles are entrenched with such ability as a result of their high
surface area to volume ratio as against macromolecular counter-
parts, magnetic, tuneable thermal as well as optical and electrical
attributes. Different shapes and sizes can be compounded either
as solid or hollow with desirable surface chemistry as well as
chemical compositions which can be manipulated with endoge-
nous and exogenous stimuli. Nanoparticles have the tendency to
prevail over the chemical as well as biological barriers inherent
in human body as a result of its multifaceted characteristics which
permitting diagnostic localisation, augmented therapeutic as well
as potency for higher biocompatibility and lower invasiveness aim-
ing at improving the patient qualify of life. Although, pre-clinical
results have been fantastically promising, the full translation pro-
spect of nanoparticles are yet to accomplished [20].
3.2. Therapeutics
Nanotechnology has been discovered to have several prospects
in biomedical applications and is currently receiving extensive
development and as a vast scientific interest. It was ascertained
that nanotechnology can be integrated with cellular therapy tech-
niques to combat the limitations occasioned by conventional ther-
apeutics. Nanoparticles such as colloidal zinc oxide were
established to have contained antibacterial properties to overcome
a large number of pathogens [22]. Zinc oxide nanoparticles pos-
sessed higher bactericidal activity to combat Staphylococcus aureus
as against other nanoparticles metal oxide [23]. It was further
revealed that gold nanorods has the potential to destroy patho-
genic microorganisms by applying phytothermal treatment [24].
Gold nanoparticles are more photostable, easily keyed to surface
modification and is less toxic as compared to silver. Also, gold
radiations, and this could be transferred to the attached bacterial
cells in the form of heat and could lead to permanent cellular dam-
age [25].
3.3. Medical instruments and sensory
In recent year, nanotechnology has been identified as a means
of detecting contamination, even at a minute level using nanoscale
sensors [26,27]. These nanoscale sensors had been proven to have
the capacity to measure and monitor materials developed from the
metabolism and bacteria growth substance, hence has the capabil-
ity to monitor bacterial and viral toxicity.
3.4. Nano drugs
It is pertinent to make mention of carrier-free nanodrugs which
are self-delivery drugs that are in nano-sizes and these drugs are
produced by different active agents with or without the use of inert
materials [28,29]. The active constituents that could congregate
into carrier-free nanodrug are targeting agents, photosensitizers,
as well as anticancer drugs with various techniques of therapy
etc. The following characteristics can be attributed to carrier-free
multi-agent nanodrugs:
(a) The possibility to produce all-in-one nanosystem for cancer
diagnosis and therapy can be achieved.
(b) The possibility to subdue the multidrug resistance as the
major obstacle to cancer treatment.
(c) The synergistic cancer therapy has higher tendency and
promising curative effect when compare to free multidrug
group with the same number of doses.
(d) It has excellent targeting capability with reduce toxic and
side effects without any carriers.
(e) It has tremendous drug pharmacokinetics as well as drug
loading ability which could even reach 100%.
3.5. Orthopedics
Researchers have revealed that nanomaterials possessed the
attributes to fabricate future orthopaedic implants due to the abil-
ity to reproduce as well as simulate the constituent organs of a nat-
ural bone [30,31]. The demand for bone substitutes in orthopaedic
applications is indispensable due to its promising usage in the cure
of irreversible damage of the natural as well as healthy bone. On
this note, nanomaterials played a vital role by regulating cell pro-
liferation, migration as well as differentiation asides the structural
support providing for the cell such as nano-functionalized scaffolds
[32–34].
As shown in Table 1, different bioimplants can be used for sev-
eral engineering applications. This is possible due to some promis-

Table 1
Bioimplants’ applications.

S/ Bioimplant Functions Reference

N
1 ligaments, dental assist in healing Cross
implants et al.,
2 Joint This responsible for the repairing or [36]
replacements, re-establishing the functionality of
vascular grafts disintegrated tissues
3 Intraocular lenses This responsible for correcting the
cosmetic irregularities functions
4 Bone plates, This responsible for rectifying the
sutures, heart functions of a body part
valves
Fig. 5. Comparison of nanoparticles as organic and inorganic.

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O.P. Bodunde, O.M. Ikumapayi, E.T. Akinlabi et al. Materials Today: Proceedings xxx (xxxx) xxx

ing chemical and physical properties. It was established that archi-
tectural gradient of tissues and organs can be simulated via con-
ventional metallic or non-metallic materials. Nevertheless, the
main setback of the conventional bioimplants are inability to agree
to the tissues, they are not usually in harmonious with the tissues
and as such not usually conform to the human body [35].
3.6. Spine surgery
In recent years, the debut entrance of microscopic cellular and
subcellular level was regarded as promising alternatives to macro-
scopic surgical options for the treatment. One must not shy away
from the fact that, nanotechnology is one of the approaches which
has found irresistible applications in biomedical even in the treat-
ment of spine pathologies [2,37,38]. This technology gave birth to
the ground-breaking materials and devices by nanoscale (10 9 m)
activity on matter. The effectiveness of this technology can be
related to the drug carrier or other components and can operate
on the basis of synthesizing complex structures from particles of
atomic size, rather than breaking down the complex materials into
smaller parts. This article focuses on the clinical analysis of the
advantages of nanotechnology in the treatment of spinal pathology
and addresses the effectiveness of the current literature on this
technology [39] [Jain, 2007]. The summary of nanotechnology
applications as shown in Table 2, the table shows various indus-
tries and product explored using nanotechnology methods.
4. Methodology and systematic review design
The study conducts a systematic review of studies pertaining to
nanomedicine for drug delivery and various other applications of
nanotechnology relating to human health and therefore recom-
mending a nano-doctor, who can carry out minimal invasive oper-
ations or perhaps much less invasive operations. This focus is
motivated by the fact that nanomedicine is growing geometrically
around the world with some well-established innovations based
on nanotechnology. However, works related to the invention of
an autonomous nano-doctor are limited and still open for a system-
atic research. All the present studies on nanomedicine as basically
for targeted drug delivery, diagnostic system, destruction of tissue,
attacking of virus, fighting autoimmune diseases, therapy enhance-
ment, synthetic vaccines, blood clotting, etc.
5. Advantages, disadvantages, and challenges
5.1. Advantages of nanotechnology ditto nanomedicine
5.1.1. Electronics and computing
Over the years, nanotechnology has been revolutionised by a
field of electronics and computing. Quantum dots are tiny-
producing cells have been purposely used for display screen as well
as illumination. It was revealed that silicon chips which contains
more than millions of components are already reaching its limit;
at a particular point in time, the circuit will not work appropriately
because it is so small since the molecule is out of place [40]. On this
premise, nanotechnology will enhance the accurate construction of
circuits on an atomic level. It must be aware that nanotechnology
can excellently revolutionized many aspects of electronics prod-
ucts, procedures as well as applications. Several areas stand to gain
from the continue development of nanotechnology when is fully in
place in respect to electronic products, most of the areas of benefits
are plasma displays, nano transistors, OLED, quantum computers,
nono diodes and many more [41].

Table 2
Nanotechnology medicine’s products.

S/ Manufacturer Product name Purpose Specific purpose References

N
1 DNA Diagnostic testing Diagnostic Generally, for diagnosis tests Wagner et al., [42]
Medicine system system
Institute
2 MagArray Diagnostic testing Li et al., [21]
system
3 T2 magnetic Diagnostic testing using magnetic nanoparticles Pankhurst et al., [43]
Biosystems nanoparticles
4 Cristal Polymeric micelle Drug Delivery Drug Delivery to tumors Kalhapure &
Therapeutics nanoparticles Renukuntla, [44]
5 CytImmune Gold nanoparticles Responsible for effective delivery of the drugs to tumors Zhang et al., [24]
6 Sirnaomics Sirnaomics Nanoparticles responsible for the effective discharge of siRNA Zhou et al., [45]
7 SignaBlok SignaBlok Assist in the delivery of drugs and imaging agents Mark et al., [46]
8 Starpharma Dendrimer Improving solubility for drug delivery systems Najafi et al., [47]
nanoparticles
9 Taiwan Liposome Drug delivery using lipsomes Crommelin, et al., [48]
Liposome
10 BlueWillow Nanoemulsions Destruction of Responsible for Nasal delivery to overcome the effects of viruses (like colds as Bai et al., [49]
tissue well as flu) or via the skin to deal with effect of bacteria
11 Nanobiotix Tumor nanoparticle Target tumor cells, uses XRAYS to generate electrons that will be responsible Han et al. [50]
for localized destruction of tumor cells.
12 Nanospectra AuroShell particles Used for thermal destruction of cancer tissue Mirjavadi et al., [51] &
(nanoshells) Karami et al., [52]
13 NanoViricides Nanoviricides Attack virus It is designed to attack virus particles [53]
particles
14 Parvus Imomuno Fight Nanoparticles designed to fight autoimmune diseases Cirstoiu-Hapca et al.
Therapeutics nanoparticle autoimmune [54]
diseases
15 Nanoprobes Gold nanoparticles Therapy It is used for radiation therapy enhancement Zhang et al., [24]
enhancement
16 Selecta Synthetic vaccines Synthetic Nanoparticle based synthetic vaccines Dobrovolskaia and
Biosciences nanoparticle vaccines McNeil, [55]
17 Z-Medica Medical gauze with Blood clotting It helps blood clot faster in open wounds. McGann et al., [56]
aluminosilicate

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O.P. Bodunde, O.M. Ikumapayi, E.T. Akinlabi et al.
5.1.2. Energy sector
It has been revealed that energy sector can benefited from nan-
otechnology in such a manner that it will transform the production
and consumption rate of our energy. It is evidential that nanotech-
nology will guide the construction of solar panels and any other
related equipment thereby reducing the cost of construction and
make the solar power readily available and this will make energy
storage devices to be more efficient [57]. Nanotechnology will pave
ways for new techniques of producing and storing energy. The cre-
ative ideas of developing more efficient energy storage, energy-
generating, as well as energy-absorbing products in a reduce and
in more effective devices will be alarming with this technology.
Products like fuel cells, batteries as well as solar cells can be pro-
duced in smaller sizes and be more effective with this technology
[58].
5.1.3. Manufacturing sector
Nanotechnology has made it possible to manufacture different
products in different sizes, shapes and forms, faster, safer, stronger,
cleaner, smarter and lighter with accuracy. Nanotechnology has
made it possible for different materials to be recolonized in manu-
facturing sectors. Nanomaterials could come from four aspects
such as metals, polymers, composites as well as ceramics. How-
ever, unlike these other materials, they are not distinguished based
on their chemistry, but rather size. Nanotechnology has begun the
development of new materials that will change many aspects of
manufacturing sector. Nanoparticles as well as nanotubes are such
developments in which particles and tubes exhibit a few atoms
across, similarly, aerogel. These materials are very strong and are
light in structure with outstanding insulating properties which
could enhance the development of new products with dynamics
techniques. Beside this, nanorobots and nanofactories will also be
a useful tool in the construction of novel materials and objects [59].
5.1.4. Medical field
Since nanotechnology has made debut entrance into the medi-
cal world, it has helped in creating smart drugs which helps in cur-
ing diseases and illness faster than traditional drugs without any
side effects. In recent years, nanotechnology has been channelling
its expertise to some areas of medical applications such as bone
repair, tissue regeneration, immunity, and cure for ailments such
as diabetes, cancer as well as other life-threatening diseases. Nan-
otechnology has the capability to liberate major advances in med-
icine. Blockages in patient’s arteries could be cleared by Nanobots.
Surgeries can be done faster and more accurate the nanotechnol-
ogy is employed and at the same time repaired injuries cell-by-
cell. It could be possible to fix damaged genes by heal genetic con-
ditions. Finally, nanotechnology could be employed to refine drug
production in such a manner that it is tailored towards molecular
level by reducing the side effects and making them more effective
[24].
5.2. Disadvantages of nanotechnology/nanomedicine
Despite lots of benefits that can be derived from nanotechnol-
ogy because of its increasing research and advancements in medi-
cal surgery, food packaging, electronics and computing, medicine,
manufacturing, textile as well as energy generation. There is some
capability of engineering evil potentials that are still inherent in
nanotechnology industries. A system responsible for checks and
balances to assist in overcoming the mishandling of scientific
research and capabilities exists. Notwithstanding, nanotechnology
has offered lots of possibilities and advancements in recent times,
there exist certain severe discussions on the prevalence of the nan-
otechnology in the world. Some potential risks with the disadvan-
tages have been anticipated in the nanotechnology in recent time.
6
Materials Today: Proceedings xxx (xxxx) xxx
It can never be denied that nanotechnology has greatly increased
the standard of living across the globe, nevertheless, it was estab-
lished that it has caused lots of pollution which includes air pollu-
tion, as well as water pollution [57,58]. This type of pollution is
known as nano pollution and it is very dangerous to living organ-
isms. The following are the disadvantages nanotechnology can
offer:
i. Nanotechnology has caused lots of unemployment in the
fields where it has experienced tremendous advancements
such as manufacturing, traditional farming as well as indus-
trial sectors due to its vast research and development which
is one of the biggest disadvantages. It has been revealed that
nanotech devices and machines have replaced human efforts
which are prone to errors, because nanotech devices are fas-
ter, smarter, and more accurate [60].
ii. Nanotechnology has made possible for some infinitesimal
recording devices, which would be virtually undetectable.
Frankly speaking, nanotechnology can be weaponized. The
development of novel atomic weapons would be easier to
manufacture. Another way to achieve this, is the develop-
ment of a computerized bullet also known as ‘‘smart bullet”
which can be controlled and aimed accurately at the targets,
likewise atomic bomb. All the development will make a
defence industry especially military and other arms to be
more effective and efficient in their operations, nevertheless,
if they are wrongly handed or fell into wrong hands, the con-
sequences would be disastrous [59]. Since atomic weapons
can be developed via nanotechnology, it has become move
powerful and destructive in its operation. Nanoparticles
could potentially have a toxic effect [48].
iii. It is most unlikely to achieve mass production of nanotech-
nology materials. How likely can nanotechnology achieve
the procurement a truthful and certifiable molecular manu-
facturing machine for every household?
iv. It has the potential for mass poisoning over a period. Prod-
ucts made from nanotechnology could cause great health
challenges to the consumers of the products and this can
be enormous. It is mostly likely that the nanoparticles
inhaled can settle at the brain and lungs whereby leading
to great increase in biomarkers for stress response and
inflammation. Experts in nanotechnology had recent
debunked some of the extravagant negative future scenarios
in the field. One of these scenarios was so-called ‘‘gray goo”,
in which nanobots that are self-replicating consume what-
ever that is around them in order to make copies of them-
selves. This scenario was widely discussed over the years
but as it is today, it is no longer considered as a credible
threat. Notwithstanding, nanotechnology may pose some
negative and adverse effects on the environment through
the release of new toxins and poisonous pollutants [59].
v. Inadequate knowledge of nanotechnology will make it
impossible to manufacture. It is factual that materials can
be developed from nanotechnology. It is therefore essential
to understanding the impact of the products of these devel-
oped materials on the nanoscale.
vi. The cost of developing and servicing the nanotechnology
devices is very alarming and to assemble the nanoparticles
materials in different shapes, forms and sizes may require
experts and many technologies.
vii. It is most likely that nanotechnology will cause great
changes in the economy like other previous technologies
before it. However, it was revealed that products made from
nanotechnology will be very expensive at initial entering
being luxury products and specialist items, by and large, as
the production increases more markets will experience its
O.P. Bodunde, O.M. Ikumapayi, E.T. Akinlabi et al.
impact. Some materials and technologies will be outdated
because the materials they specialise are out of business.
Great changes experiencing in the manufacturing processes
due to nanotechnology may lead to job losses [36].
viii. There are some products that developed sporadically with
their instant performance accelerated the decrease of certain
markets such as oil and diamond due to the low value of oil
as well as diamond. The availability of a promising alterna-
tives has reduced the demand because it was established
that alternates have higher performance and the use of fossil
fuels are not needed. Nanotechnology has made the dia-
mond to be less valued because of its mass production
through nano-technique. The production of bulk products
at molecular scale is now possible through nanotechnology
since the decomposition can easily be carried out on them
to give room for new components [59].
ix. Setting up of nanotech plant involve high risk since the man-
ufacturer will invest so much to start up the business in
order to satisfy the demand and interest of their customers
and if peradventure the business fails, the manufacturers
bear a great loss. The maintenance cost of the nanotech plant
as well as the product is so huge, and the original product
cannot be regained since it will serve as double cost for
the manufacturers.
x. Nanotechnology can generate practical problems like the
mass production of coal as well as petroleum. Nanotechnol-
ogy has been responsible for the crashing of some small
industries of their sub products involving enormous materi-
als loss resulting to low quality of sub products of petroleum
as well as coal in the markets due to complete used of nano
particles [36].
5.3. Present challenges faced by nanosurgery/nanomedicine
A successful metamorphosis of nanomedicine from the tradi-
tional and pre-clinical concepts to a demonstration of nanosurgery
in the clinic is still a great challenge. Several obstacles which could
retard the growing field of nanotechnology as applicable to surgery
have been identified as top scientific steeplechases in bringing
nanoengineered products to surgical patients. Such hurdles are
diagrammatically shown in Fig. 6. The following cross-roads barri-
ers have been identified to affect a successful metamorphosis to
nanomedicine, they are consequently potential issues for nanosur-
gery or issues that could deter the emergence of a nano-doctor.
Fig. 6. Challenges of nanomedicine.
7
Materials Today: Proceedings xxx (xxxx) xxx
5.3.1. Biological barriers
It has been established that before the drugs can get to the site
of the disease on the patient, a few biological barriers must be
overcome through nano-formulation [61,62]. Oral nanoparticles
as a case study, must be stable in the gastrointestinal tract, the ten-
dency to enter intestinal epithelium and the capability to maintain
an increase systemic bioavailability of drugs after crossing differ-
ent obstacles [62,63].
5.3.1.1. Safety barriers. In recent years, safety issues have been
raised on the use of nanomedicine, especially the injection of
nanoparticles which are widely used in medicine. This necessitates
addressing issues of human health toxicity and compatibility
[64,65]. The nanoscale element of nanomedicine-designed prod-
ucts may be used to mimic intracellular organelles or biomolecules
such as protein, polysaccharide, and biological enzymes involved
in cell signalling. These could lead to harmful biological interac-
tions. The good news about this is that, nanotoxicology is an
emerging and independent field of research which and aid the doc-
umentation of toxic nanoparticles and can be used for other appli-
cations rather than injection into human body [55,66]. Several
information and data stating and informing the toxicity of the
available nanoparticles are being documented by the researchers
in the field of nanotoxicology.
5.3.1.2. Regulatory barriers. There is a lack of guidance in nanome-
dicine administration and examination, nanomedicine therapeu-
tics, and targeted drug delivery processes. A lack of guidelines
will only allow regulatory decisions that are biased, arbitrary,
and based on an individual benefit and risk assessment [67]. The
regulatory process is also more time consuming and requires
high-level expertise in nanotechnology, i.e. high-level experience
in emerging technologies, which can lead to delays in regulatory
guides. Regulatory issues are of prime significance for the inven-
tions of ground-breaking nanotechnologies tools to analyse and
control the quality of the products of nanomedicine which is
incomparable with the clinical trials as well as the process
approval. Emphatically speaking, the characterizations and the
evaluation of the quality of the products of nanomedicine requires
detailed guidelines to serve as a mirror for their operations [68].
However, various professional are working on the definitions,
guidelines for nanomedicine and its several areas of applications
[69–70].
O.P. Bodunde, O.M. Ikumapayi, E.T. Akinlabi et al.
Fig. 7. An integration of nano-tool to develop a nano-doctor.
5.3.1.3. Manufacturing barriers. Most nanoparticles are complex 3D
products having some unique arrangements of multiple compo-
nents, which make the physical requirements, chemical require-
ments, manufacturing, and control process very demanding.
Scaling is a key issue for successful manufacturing of nanomedi-
cine product and services. It is important to control and keep con-
stant the stability of physicochemical properties on a batch-to-
batch basis [1], before carrying out nanofabrication. Scaling to
small sizes are generally difficult processes and the success of
nanofabrication is a discussion of reproducibility of well-
characterized nanoparticles.
An in-depth understanding and identifying the components and
how they interact with each other in the early development will
assist in defining the key features greatly, such as the critical steps
and analytical criteria, to ensure reproducibility of the product dur-
ing mass production or manufacturing of the nanoparticle in inter-
mittent manner. Generally, nanoparticle preparation methods are
categorized as, ‘‘top-down” and ‘‘bottom-up” approaches [71]. In
the manufacturing of nano-entities, the top-down techniques
require the grinding of particles from larger ones to smaller pieces
via milling methods. Contrary to that, bottom-up techniques
require the assembling of smaller components into a functional
super-assembles. For examples, several monomers developed into
a polymer, and molecular self-assembly developed to a single or
multi-molecule component into a usable nanostructure by natural
driving [72]. In the course of nanomedical formulation process, the
following parameters are usually engaged: filtration, milling,
lyophilisation, emulsification, centrifugation, high-speed homoge-
nization and crosslinking etc. It is therefore to essential to know
which of the parameters and approaches are best suited to scale
up at the lab or small-scale stage and to determine which process
conditions will benefit the development. The targeting moieties,
nanomaterials, the type of organic solvent, drugs, temperature,
pressure, and pH are suitable parameters that can involve [72].
8
Materials Today: Proceedings xxx (xxxx) xxx
5.3.1.4. Analysis and characterization barriers. When compared with
traditional medicine products, nanomedicine products are 3-
dimensional sophisticated products comprises of various compo-
nents and each part of the component functions uniquely [73].
However, it will need more complex and accurate analytical testing
methods to detect, characterise and evaluate each component
fully; and to quantify interrelationship among these components
in relation to biological as well as physiochemical properties
[74]. This scenario is one of the challenges encountered during
nanomedicine development which is not limited to technical
aspect but also regulatory perspective. Frankly speaking, the most
cogent nanomedicine physicochemical properties are surface prop-
erties, charge, composition, size, stability, structure, as well as
porosity [75,76]. Variability properties of nanomedicine products
made it difficult for its characterization and this also goes to char-
acterization of storage as well as stability properties of nanomedi-
cine. It was noted that polymer and lipid possessed promising
attributes of biodegradable materials and as such are widely inte-
grated in nanomedicine products development. This promising
property of biodegradable will change nanomedicine products
properties in the course of storage either in the form of solutions
or as a lyophilized powder [77,78]. Therefore, biodegradable mate-
rials must be well scrutinized and assessed for quality assurance
and ensure that it meet up with guidelines and set-up standard
to be used for the development of nanomedicine products.
6. Summary, conclusion, and recommended studies
In summary, in the areas of drug delivery, therapy and treat-
ment, nanotechnology has made significant contributions to clini-
cal medicine, and many other ground-breaking heights and
especially new technologies will continue to emerge following
the same basic design principles. This study extensively examines
numerous nanotechnology milestones and focuses in particular on
O.P. Bodunde, O.M. Ikumapayi, E.T. Akinlabi et al.
the potential realization of a ‘‘nano-doctor” that is inevitably still in
the infancy stage and needs to resolve many obstacles to human
anatomy requirements, technological designs, IoT integration,
machine learning and AI algorithms before it is accepted for com-
mercialization. A need for designing and engineering nanostruc-
tures with suitable physicochemical properties and associated
metabolic behaviours mirroring directly from humankind, enhanc-
ing reproducible automation and industrial operations, and identi-
fying a robust characterization analysis tool is unavoidable. If the
scientific tool integrated in Fig. 7 is adopted, there is a possible
of developing a nano-doctor which can be controlled virtually with
the 4IR technologies. It is recommended to harness 4IR with the
existing nanotechnology method to develop the so-called nano-
doctor.
Declaration of Competing Interest
The authors declare that they have no known competing finan-
cial interests or personal relationships that could have appeared
to influence the work reported in this paper.
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