1 Int. J. Biomol. Biomed.

International Journal of Biomolecules and Biomedicine (IJBB)

ISSN: 2221-1063 (Print), 2222-503X (Online)
http://www.innspub.net
Vol. 14, No. 3, p. 1-10, 2022

REVIEW PAPER OPEN ACCESS

Assets and liabilities of nanotechnology

Zakia Kanwal, Maheen Wajid, Nimra Noman*, Sumaira Pervaiz

Department of Zoology, Lahore College for Women University, Jail Road, Lahore, Pakistan

Key words: Nanotechnology, Nanoparticles, Biomedical applications, Gene delivery, Bioimaging,

Magnetic hyperthermia, Nanotoxicity, Oxidative stress, Lipid peroxidation

Article Published: 10 June 2022

Abstract

In recent years, nanotechnology played a central role in research and has shown its significant impact on the
field of medicine. Nanoparticles are more efficient than other bulk materials. Novel nanoparticles possess
properties like high magnetic proneness; biocompatibility and chemical stability make them efficacious to be
use in biomedical field as in treatment and diagnosis of various diseases, bioimaging, hyperthermia, drug
delivery, gene delivery and photo ablation therapy. Although, nanotechnology is providing us benefits in many
technology and industry sectors i.e., medicine, food safety, environmental science, information technology etc.
but besides its positive aspects, it can prove to be a cause of nanotoxicity as well. The toxicity of nanoparticles
can be assessed by their size, shape, surface charge, surface coating etc. Humans and cell cultures can be
affected by nanoparticles as they can cause lipid peroxidation, oxidative stress, DNA damage and eventually
cell death. This review article encompasses pros and cons of nanotechnology and focuses on an attempt to
promote its advantageous use and to reduce its hazardous effects in different fields.
*Corresponding Author: Nimra Noman  [email protected]

Kanwal et al.
2 Int. J. Biomol. Biomed.

Introduction In this method drug is directed to a particular area

Nanoparticles where tumor is present and thus it's an efficient
Nanoparticles as the term narrate are nano-size (10-9) method of delivering drug with reduced side-effects.
solid colloidal particles which have gained Nanoparticles provide an error free and effective
significance due to their particular utilization in every delivery to the targeted area than larger micro-
field of science. Nanoparticles have a number of molecules. For delivery they are either integrated in
properties such as chemical reactivity, particles' matrix or may be attached to the surface of
biocompatibility, energy absorption, biological particle. Mostly drug is delivered by magnetic
mobility and high magnetic sensitivity that nanoparticles as they are easy to control and more
distinguish them from bulk materials. In the past biocompatible than the other nanoparticles.
years, nanotechnology has revolutionized the field of
nanomedicine and emerged as important players in Gene delivery is narrated as a process in which
modern medicine. (Shashi, 2007). foreign genes are inoculated into living cells and it is
designated as important advancement in gene
Categorization of Nanoparticles therapy. Viral vectors still dominate this field but an
According to their applications in biomedical field ever-increasing attention is being diverted toward
they are classified into four different nano-systems as non-viral vectors as a measure to deal with the safety
described in Fig. 1. concerns of viral vectors (Mody et al., 2010)
• Metallic nanoparticles such as gold and silver
• Bimetallic nanoparticles as Fe–Co, Fe–Ni and Fe–
Pt nanoparticles
• Metal oxide nanoparticles as TiO2
• Magnetic nanoparticles include Fe3O4, Mn–Fe2 O4 etc.

Fig. 2. Schematic diagram representing Targeted

drug delivery to tumor cell.

Nanoparticles as effective drug carriers

Fig. 1. Classification of Nanoparticles. Silver nanoparticle due to its ultra-small and
antimicrobial activity as potent efficient agent against
Biomedical Applications
infection size as high surface area and increased
In this section of review, the most interesting and
reactivity with active functional structure. The surface
investigated applications of nanoparticle in
ligand coating of silver nanoparticle incorporated
biomedical field are described with special emphasis
drug as drug delivery vehicle enlightens its sustained
on their therapeutic effect.
release and ensures less complicacy (A, Mandal et al.,
Targeted Drug and Gene delivery 2017). Ag nanoparticles have properties to be used as
Targeted drug delivery is a technique that is drug delivering agent to deliver doxorubicin along
developed as a possible substitute of chemotherapy. with alendronate which are often used to treat cancer

Kanwal et al.
3 Int. J. Biomol. Biomed.

and to slow down the process of dissolving bone cascade of therapeutic response by successful
tissues to cervical cancer cells, respectively conversion of prodrug 5-Flurocytosine to 5-
(Benyettou et al., 2015). Lee and his co-workers Fluorouracil and nanoclusters of silver and gold. Cell
produced conjugates by using AgNPs with demise resulted by formation of reactive oxygen
oligonucleotide. And they evaluated that they show species and the cell demise was apoptosis mediated
high cooperative binding properties (Lee et al., (Dutta et al., 2016). Anti-fouling magnetic
2009). Ferrous platinum nanoparticles when loaded nanoparticles have properties that make them
with an anti-cancer medicament can be used as effective carriers for siRNA delivery to cells and it was
carrier to target cancerous gastric cell lines. done by generating IONP siRNA nano-carriers. The
Fabrication of Fe–Pt nanoparticles was done by transfection efficiency revealed the non-toxicity of
giving Ferrous platinum/ Poly di-ally di-methyl carriers to cells and it was measured both with and
ammonium chloride silica composite particles a without magnetic field using human neuroblastoma
hydrothermal treatment. Cancer cell growth of cell SHEP cells (Boyer et al., 2010).
line was prevented by Fe–Pt–Dox capsules with 70%
destruction of cancer cell line.

Wu et al. (2011) studied that titania nanoparticles

(mesoporous in nature) can be used for drug delivery
by preparing them through controlled hydrolysis. He
investigated the cytotoxicity on cell line of breast
cancer cells of human. It resulted in favor of
nanoparticles providing evidence of more compatibility
along with high propinquity for those compounds that
contain phosphate in them like DNA etc.
Fig. 3. Gene delivery by Magnetic Nanoparticles.

Role in Gene Delivery

Bioimaging
Various diseases that occur in humans are due to
Bio imaging techniques are used to detect or diagnose
mutations or deletions in genes which result in
a disease. It includes techniques like Ultrasound,
metabolic pathway disorder and disturbance in cell
MRI, computerized tomography etc. The basic need
cycle regulation, protein function and its structure,
to employ contrast is just to spot area of interest and
function of receptor, and cell skeleton. Gold
also help to differentiate and identify healthy group of
nanoparticles that are cationic in nature can be
cells from the diseased one. Toxicity is one of the
prepared in the presence of 2-aminoethanethiol by
major concerns for using contrasting agents for MRI
reducing HAuCl4 with NaBH4 which result in
and CT imaging. Many researches have been done
formation of a multiple in collab with DNA from
that encourage the use of nanoparticle mostly core-
plasmid and can be used to transfect cultivated cells
shell nanoparticle for their use as contrast agents in
(Niidome et al., 2004).
bioimaging techniques as they have an increased
A cBSA nanoparticle system that contained a complex imaging time as compared to other agents and are
of silver and gold nanoparticles was devised to deliver biocompatible too. They give good quality resolution
suicide gene (therapeutic) to HeLa cells. With cBSA images of internal organs (Mccnamara et al., 2017)
silver and gold nanocluster composite NPs which are
loaded with plasmid DNA, combinatorial therapy was Role of Nanoparticles in Bio imaging
accompanied. A suicide gene named as (CD-UPRT) Ferrous and Platinum nanoparticles can be used as
was successfully delivered by the help of composite contrast agents for diagnosis of brain tumors.
NPs that were loaded with pDNA, into cells initiated a Ferrous-Platinum NPs coated with L-cys assessed

Kanwal et al.
4 Int. J. Biomol. Biomed.

against C6 glioma cell lines from rat, SGH44 cell line results like high biocompatibility to be used in
and U251 cell line from humans. These were used as hyperthermia therapeutic technique. Fe3O4 and γ-
contrast agents for CT and MR imaging. The cystine Fe2O3 have a low magnetic coercivity while ε-Fe2O3
coated ferrous platinum nanoparticles found to be exhibits a huge coercivity. The heating power of ε-
compatible as cell viability represented no difference Fe2O3 nanoparticles as compared with γ-Fe2O3
(Liang et al., 2015). To determine toxicity studies on nanoparticles of comparable size (∼20 nm) was
cell viability were accomplished by study on HeLa measured. In contrast, γ-Fe2O3 nanoparticles heat
cells obtained from cervix with Ferrous-Platinum more efficaciously within the high frequency range
NPs. From (MR) signal enhancement studies, (400–900 kHz). No toxicity was observed by cell
researchers deducted that amphiphilic Ferrous- culture lines at all. ε- γ-Fe2O3 nanoparticles were
Platinum nanoparticles provide more effective result proved to be slightly superior to Fe2O3 nanoparticles
than other nanoparticles when used in place of other in human magnetic hyperthermia applications. Thus
contrast agents (Yang et al., 2010). ε-Fe2O3 nanoparticles open the route for magnetic
heating (Gu et al., 2010).
Magnetic Hyperthermia and contribution of
Nanotechnology
It is a technique in which heat is used to kill or
dissolve destroy cancerous cells and tissue. It is done
by raising the temperature up to 40–47 °C of infected
or diseased area. This technique kills cancer cells but
not the healthy ones, which is an advantage of this
technique. Diseased cells or tumor cells are sensitive
to temperature so cell apoptosis is initiated when cells
are treated at a temperature of 40-47°Celsius and this
is termed as hyperthermia effect. Heating cell up to
47–49 °Celsius can kill the cells and this phenomenon Fig. 4. Process of Magnetic hyperthermia technique.
is as termed as thermo-ablation. Hyperthermia
treatment with radiotherapy and chemotherapy in Photo ablation Therapy and Role of Nanotechnology

collaboration is used to treat cancerous cells. The Photo ablation therapy involves use of a laser beam to

material properties along with cytotoxicity and remove cancerous cells and lesions by irradiation as

magnetic isotropy of one-dimensional iron nanowires upon heating with a laser beam, the tumor cell or

were explored by analyzing effect on EMT-6 cells. By tissue got vaporized which causes the destruction of

application of magnetic field and using reducing tumor or cancerous and thus it is an effective

method, these nanoparticles were synthesized and it treatment for cancer. It is classed as photodynamic

was concluded that iron wires were effective agent to therapy and photo thermal therapy, both of which are

be used in hyperthermia treatment (Lin et al., 2013) used as a treatment for killing cancerous cells in body
at a target site. Photodynamic Therapy uses light
Seeman and his workers in 2015 investigated the role sensitive compounds mainly non-toxic called
of Fe–Pt NPs coated with tungsten oxide to be used in photosensitizers. When exposed to light, a photon of
treatment technique of magnetic hyperthermia. particular wavelength, these show toxicity. This is
Preparation and annealing of SiW11O39-coated Fe–Pt accustomed to target effective cells like cancer.
nanoparticles was done at 700 °C. Magnetometry and Photodynamic Therapy process is characterized by
magneto-caloric measurements measured the heating the exposure of certain nanoparticles which are
effect as well as magnetic characteristics of these mostly photosensitizers, like TiO2 nanoparticles, are
nanoparticles. It was concluded that tungsten oxide- exposed to light due to which electrons and holes are
coated Ferrous-Platinum nanoparticles show effective created at a particular wavelength.

Kanwal et al.
5 Int. J. Biomol. Biomed.

Reactive oxygen species and oxygen form when these nanoparticles in mice and it also inhibit tumor growth
light reduced electrons and holes react with the water with increased survival time (Wang et al., 2011). Folic
and hydroxyl ions. (Dickerson et al., 2008). acid functionalized Fe–Pt nanoparticles can be used
Inevitable necrosis occurs due to production of these to EMT-6 breast tumor cells as it was studied by Chen
species. Tumor cells are exposed to radiation by near and his coworkers. Near Infrared laser was used for
infrared light. Heat which is produced by light causes activation of functionalized Ferrous-Platinum
hyperthermia. Necrosis results due to hyperthermia. nanoparticles. Results depicted zero toxicity along
Titanium dioxide nanoparticles are used because they with high biocompatibility to cell. Upon irradiation by
have many attractive properties like biocompatibility the laser, the plasma membrane of cancerous cell got
to body, have chemical stability and prominent photo ruptured which indicate that this method is useful for
catalytic activity. targeted cancer therapy (Chen et al., 2013).

TiO2 nanoparticles when exposed to light causes the Nanoparticle use in fields of medicine is increasing as
growth inhibition tumor cells and it was evaluated by in current century researchers have done much work
Wang and his co-workers on glioma cells. Study was on its uses in different areas of medical science which
conducted in vivo and in vitro on Uppsala 87 is one of important concern for scientist as to devise a
Malignant Glioma cells and nude female Bagg Albino- cheap and more appropriate replaceable agent for
c mice. These mice were injected with glioma cell diagnosis and treatment of diseases and for use in
lines and the TiO2 suspension under their skin and various sub-fields as it is described below in given
cytotoxicity was determined too. It was found that no analysis on researches done by scientist to assess use
cytotoxic effect was associated with TiO2 of nanoparticles in biomedical field.

Table 1. Biomedical applications of Nanoparticles.

Nanoparticles Use in Biomedical Field References
Cationic BSA templated Au–Ag bimetallic nanoclusters as a Mandal, A. K. 2017.
theranostic gene delivery agents for HeLa cancer cells
Use of silver nanoparticles for effective delivery of doxorubicin Benyettou et al., 2015.
and alendronate to tumor cells
Silver NPs
Silver NPs used as drug delivery vehicle against infections Dutta et al., 2016.
PVP-coated silver nanoparticles cause anti-leukemia activity Guo et al., 2013.
Colloidal silver NPs shows anti-tumor activity on human breast Franco-Molina et al.,
cancer cells 2010.
Used in anti-cancer drug delivery system mediated magnetically Fuchigami et al., 2012.
One-pot synthesis of amphiphilic superparamagnetic Ferrous Yang et al., 2013.
Platinum nanoparticles and magnetic resonance imaging in vitro
Biocompatibility and Magnetic heating properties of tungsten- Semann et al., 2015.
oxide coated Ferrous Platinum core–shell nanoparticles
FePt NPs
Use of femto second-laser-excited Ferrous Platinum Chen et al., 2013.
nanoparticles in Photothermal cancer therapy
L-cysteine-coated Ferrous Platinum nanoparticles for use in Liang et al., 2015.
MRI/CT imaging as contrast agent for glioma
siRNA delivery by anti-fouling magnetic nanoparticles Boyer et al., 2010.
Magnetic Measurement of morbidity and quality of life during Johannson et al., 2007.
NPs thermotherapy using magnetic nanoparticles in locally recurrent
prostate cancer
Transfection ability amine modified gold nanoparticles into Niidome et al., 2004.
cultivated cells.
Gold NPs
Near-infrared plasmonic photo-thermal therapy of squamous Dickerson et al., 2013.
cell carcinoma by gold nanorods
Iron Effects of iron nanowires on hyperthermia treatment Lin et al., 2013.
Nanowires
TiO2 can increase survival rate in glioma-bearing mice Wang et al., 2011.
Titanium NPs
Photocatalytic treatment of cancer by TiO2 Lagopati et al., 2010

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6 Int. J. Biomol. Biomed.

Nanotoxicity and Nanomaterials and in vitro (cell cultures). In vivo tests prove to be
The toxicity caused by nanomaterials is termed as more prognostic for human effects but they seem to
nanotoxicity. Whereas, it remits to the hazardous create some hinderance due to biochemical and
impacts on living organisms and their environment physiological differences among the species. So, in
after an exposure to engineered nanoparticles. It can vitro testing is usually preferred due to inexpensive,
be classified as biological as well as environmental coherent and reliable outcomes. In vitro testing is
toxicity depending upon the target of nanoparticles. performed by performing different assays. For this
Different nanomaterials (i.e., nanofiber, carbon purpose, those cell lines are selected which present
nanotubes, nanoparticles etc.) are being used in the great reliability, stability and homogeneity in tests
field of nanotechnology but nanoparticles are most and results (Drasler et al., 2017). NP toxicity
commonly used, of which all three dimensions are assessment results indicate the hazardous effects of
equal to each other (Walters et al., 2016). different NPs at different levels of cellular
organization. Thereby, different lethal and sub-lethal
Entry routes of nanoparticles in the human body effects have been observed such as cell mortality,
Nanoparticles mostly enter into the body via skin, developmental malformations, oxidative stress, lipid
respiratory tract and gastrointestinal tract. Through peroxidation, alteration in gene expression etc. NP
different exposures, nanoparticles get access to the toxicity causes the formation of reactive oxygen
human body i.e. species (ROS) and free radicals that further induce
oxidative stress, lipid peroxidation and DNA damage.
Inhalation exposure
Nanoparticles enter into the human respiratory tract
via inhalation. The size of nanoparticle and its
spreading pattern decides that in which part of the
respiratory tract it will reside. The defensive
mechanisms of respiratory tract (mucociliary pathway
and macrophages) play a vital role in the clearance of
NPs, once they are absorbed into the body via
respiratory tract. Defensive system of respiratory tract
proves to be efficient in 33% elimination of inhaled
nanoparticles from the body (Sajid et al., 2015).

Dermal exposure
When the NPs enter the skin via dermal exposure then Fig. 5. Toxicity assessment of nanoparticles.
they accumulate in the stratum corneum and dermis
(Senzui et al., 2010). Sometimes, when the NPs are Toxic effects of nanoparticles

absorbed into the skin they can leak into the bloodstream. Besides revolutionizing in technology and industrial
sectors, NPs can cause hazardous effects in
Ingestion exposure environment and humans as well if they are used in
From gastrointestinal tract, NPs can be absorbed an uncontrolled way. Different nanoparticles cause
directly or indirectly through secondary ingestion different types of toxicity.
of inhaled particles. Nanoparticles are usually
ingested accidentally in the form of pesticides and Juvenile common carps (Cyprinus carpio) were

metallic compounds. exposed to two different doses (20 and 100mg/L) of

Cu-NPs for 7 days, then an increase in activity
Assessment of NP toxicity oxidative stress enzymes catalase, glutathione-S-
The toxicity of nanoparticles is assessed both, in vivo transferase and superoxide dismutase in their liver,
(in organism i.e., fishes, crustaceans, rodents etc.) gills and kidney was observed (Gupta et al., 2016).

Kanwal et al.
7 Int. J. Biomol. Biomed.

Gold nanoparticles exert cytotoxic effects in sac and pericardial edema, tail and head
mammalian cell lines. It was confirmed by apoptosis malformation were detected in zebrafish embryos,
induction and delay in cell cycle in mammalian cell when they were exposed to silica nanoparticles (Duan
lines. Gold NPs modulate cellular physical processes et al., 2013). In rats, nickel nanoparticles induced
by inducing cell signaling and several sets of gene cardiac toxicity, lung inflammation, liver and spleen
expression (Chuang et al., 2013). Sperm cells of injury after fourteen days of an intravenous injection
Rainbow trout (Oncorhynchus mykiss) were exposed (Magaye et al., 2014). Functionalized nanoparticles
to various doses (0.01, 0.1, 0.5, 1, 10 and 50mg/L) of show their interaction with polymeric membranes.
TiO2 NPs, then a significant decrease in the velocities The nanoparticles studied were composed of gold,
of their sperm cells after 10mg/L TiO2 NPs and an silver and titanium dioxide, had organic coatings to
increase in the activity of TSGH and SOD levels was capitulate surface charge either positive or negative.
observed. On the exposure of TiO2 NPs, the More than 99% rejection was detected in case of
kinematics as rainbow trout sperm cells mortality and positively charged NPs by negatively charged
their fertility values were seen to be affected (Özgür et membranes, even though pore diameters were 20
al., 2018). Embryonic malformations, including yolk times greater than NPs diameter.

Table 2. Toxic effects of different nanoparticles.

Nanoparticles Toxic Effects References
Barium titrate
Differentiation of adipocytes and osteocytes in rat Ciofani et al., 2013
NPs
Renal toxicity in rats Rana et al., 2018
Cadmium
Loss of epithelial, mucous and pillar cells in the gills of a
sulphide NPs Verma et al., 2020
freshwater fish
Carbon black NPs Oxidative stress in alveolar epithelial cells and macrophages Koike et al., 2006
Cerium oxide
Genotoxicity in untransformed human fibroblast Franchi et al., 2015
NPs
Production of free radicals lead to the disturbance of internal
Gupta et al., 2016
Copper NPs homeostasis of fish
Hepatic and renal toxicity in freshwater fish Hoseini et al., 2016
Apoptosis induction or cell cycle delay in mammalian cell lines Chuang et al., 2013
Gold NPs
Cytotoxicity and genotoxicity in mammalian cell lines Chueh et al., 2014
Magnesium oxide
Cellular apoptosis and malformation in zebrafish embryos Ghobadian et al., 2015
NPs
Nickel NPs Cardiac toxicity, liver and spleen injury in rats Magaye et al., 2014
Platinum NPs Nephrotoxicity and disturbance of kidney functions in mice Yamagishi et al., 2013
Embryonic malformations i.e., pericardial & yolk sac edema,
Silica NPs Duan et al., 2013
tail and head malformation
Erythrocyte lysis and hem-agglutination Asharani et al., 2010
Silver NPs
Hepatic toxicity in rainbow trout Farkas et al., 2010
Alterations in hepatic tissues compatible with oxidative stress
Diniz et al., 2013
in freshwater fish
Titanium dioxide DNA damage & tumor-like phenotypes in human gastric
Botelho et al., 2014
NPs epithelial cells
Mortality and fertility values of rainbow trout sperm cells were
Özgür et al., 2018
affected
Cardiovascular dysfunction in human coronary artery
Chuang et al., 2016
Zinc oxide NPs endothelial cells
Renal & hepatic toxicity in common carp Chupani et al., 2018

Contrary to this, fewer negatively charged NPs were an uncontrolled way), cause damage to membrane
less rejected (Ladner et al., 2012). Accelerated integrity and nucleic acids, protein destabilization
synthesis and use of engineered NPs elevate their and oxidation, production of reactive oxygen species
concentration in environment, promoting their (ROS) and release of various harmful and noxious
reciprocations with biotic and abiotic components of components (Bhatt et al., 2011). Magnesium oxide
ecosystem. These engineered NPs (if they are used in nanoparticles induced different types of

Kanwal et al.
8 Int. J. Biomol. Biomed.

malformations, intracellular reactive oxygen species different mechanisms is needed. For this purpose,
and cellular apoptosis in zebrafish embryo. Besides it, there should be proper check and balance regarding
a significant reduction was observed in the rate of the use of nanoparticles i.e., nanotoxicity can be
embryo hatching and their survival in a dose reduced by physical alterations (coatings) and besides
dependent manner (Ghobadian et al., 2015). it, biological method (green synthesis) should be
Significant lysis, hem-agglutination, membrane preferred to synthesize NPs.
damage, pernicious morphological alterations, and
cytoskeletal deformations were observed in human Abbreviations
erythrocytes, when exposed to silver NPs at a NPs (Nanoparticles), NCs (Nanoclusters), MRI
concentration of 100mg mL-1 (Asharani et al., 2010). (Magnetic Resonance Imaging), ROS (Reactive
Cadmium sulphide NPs induced renal toxicity in rat, Oxygen Species)
resulted in a consequential increase in Cd-MT
(cadmium metallothionein), lipid peroxidation and References
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