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MINI REVIEW
published: 09 March 2018 doi: 10.3389/fmicb.2018.
Edited by: Arunas Ramanavicius, Vilnius University, Lithuania Reviewed by: Umme Thahira Khatoon, National Institute of Technology Warangal, India M. Oves, King Abdulaziz University, Saudi Arabia
*Correspondence: Pradeep Kumar pkbiotech@gmail.com Pranjal Chandra pchandra13@iitg.ernet.in; pranjalmicro13@gmail.com
Specialty section: This article was submitted to Antimicrobials, Resistance and Chemotherapy, a section of the journal Frontiers in Microbiology Received: 10 September 2017 Accepted: 22 February 2018 Published: 09 March 2018 Citation: Baranwal A, Srivastava A, Kumar P, Bajpai VK, Maurya PK and Chandra P (2018) Prospects of Nanostructure Materials and Their Composites as Antimicrobial Agents. Front. Microbiol. 9:422. doi: 10.3389/fmicb.2018.
Prospects of Nanostructure
Materials and Their Composites as
Antimicrobial Agents
Anupriya Baranwal 1 , Ananya Srivastava 2 , Pradeep Kumar 3 *, Vivek K. Bajpai 4 ,
Pawan K. Maurya 5 and Pranjal Chandra 1 *
(^1) Department of Biosciences and Bioengineering, Indian Institute of Technology Guwahati, Guwahati, India, 2 Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research, Guwahati, India, 3 Department of Forestry, North Eastern Regional Institute of Science and Technology, Deemed University, Nirjuli, India, 4 Department of Energy and Materials Engineering, Dongguk University-Seoul, Seoul, South Korea, 5 Interdisciplinary Laboratory of Clinical Neuroscience (LiNC), Department of Psychiatry, Universidade Federal de São Paulo-UNIFESP, São Paulo, Brazil
Nanostructured materials (NSMs) have increasingly been used as a substitute for antibiotics and additives in various products to impart microbicidal effect. In particular, use of silver nanoparticles (AgNPs) has garnered huge researchers’ attention as potent bactericidal agent due to the inherent antimicrobial property of the silver metal. Moreover, other nanomaterials (carbon nanotubes, fullerenes, graphene, chitosan, etc.) have also been studied for their antimicrobial effects in order ensure their application in widespread domains. The present review exclusively emphasizes on materials that possess antimicrobial activity in nanoscale range and describes their various modes of antimicrobial action. It also entails broad classification of NSMs along with their application in various fields. For instance, use of AgNPs in consumer products, gold nanoparticles (AuNPs) in drug delivery. Likewise, use of zinc oxide nanoparticles (ZnO-NPs) and titanium dioxide nanoparticles (TiO 2 -NPs) as additives in consumer merchandises and nanoscale chitosan (NCH) in medical products and wastewater treatment. Furthermore, this review briefly discusses the current scenario of antimicrobial nanostructured materials (aNSMs), limitations of current research and their future prospects. To put various perceptive insights on the recent advancements of such antimicrobials, an extended table is incorporated, which describes effect of NSMs of different dimensions on test microorganisms along with their potential widespread applications.
Keywords: nanostructured material, antimicrobial activity, cytotoxicity, human health, antimicrobial agent
INTRODUCTION
Microbial contamination even today is amongst primal causes of morbidity and mortality
across the globe. According to reports, about half of the population in developing countries are
infested with microbial contamination and annually more than 3 million people die because
of it (Armentano et al., 2014). Despite spectacular advances in diagnostic and therapeutic
strategies, microbial infections continue to affect biomedical and healthcare sectors due to
the emergence of resistance against several available antibiotics (Murphy, 1994; Desselberger,
2000 ). Numerous factors including but not limited to human lifestyle changes, industrialization,
civil wars, and microbial genome alterations have been recognized for their involvement in
emergence or re-emergence of pathogens (Morse, 2001). Keeping
this serious issue in consideration, development of better
antimicrobial drugs has become highly imperative. Other
than aforementioned issue, microbes are also known for
deteriorating textiles, spoiling food products, contaminating
surgical instruments and causing the damage to crops. The
available conventional solutions to avert these problems are not
sufficient enough, therefore, development of better alternatives is
highly sought to secure the basic living standard of human beings.
Recent advances in nanostructure-based antimicrobial
medications have unveiled novel prospects to combat drug
resistance in microbes. Therefore, usage of NSM as an
antimicrobial agent in both particle and composite form
has gained enormous importance in recent years. Application
of NSM in biomedical domain relies on a number of unique
properties viz. optical, physical, chemical, thermal, electrical, etc.
Some of these unique properties play a crucial role in providing
medical relevance to the NSM while, the other properties
enable them to have significance in other industries (Dakal
et al., 2016). The pivotal characteristics that an aNSM should
preferably possess are broad-spectrum effect, inexpensive, high
specificity, and least or negligible susceptibility toward resistance
development (Beyth et al., 2015). Both inorganic and organic
NSMs have shown antimicrobial effects over a wide range of
microbial strains (Dastjerdi and Montazer, 2010; Li et al., 2011;
Latif et al., 2015), paving way for their potential applications in
textile industry (Dastjerdi and Montazer, 2010), food packaging
and processing industry (Duncan, 2011), agricultural products
and crop safety (Khot et al., 2012), water treatment (Li et al.,
2008 ), and construction industry (Lee et al., 2010) to prevent
damages associated with microbial growth.
In this review, we have presented a broad classification
of NSMs produced via. different synthetic approaches
along with an overview of the nanomaterials which possess
antimicrobial activity. Though, it is practically impossible to
present a comprehensive overview on all NSMs including their
FIGURE 1 | (i) Illustration representing classification of nanostructured materials used as antimicrobials and (ii) depiction of various forms of nanostructured materials and their morphology.
method of synthesis, characterization techniques, and mode of
antimicrobial activity in this review. However, we have tried
to present a report which clearly heralds the current scenario
of application of aNSMs in widespread domains along with
inadequacies of current research and future prospects of NSMs
as antimicrobial agents.
CLASSIFICATION OF NANOSTRUCTURED MATERIALS
A wide variety of materials exist today that is colloquially
considered as NSMs, but the term NSM validates only those
materials which belong to 1–100 nm range. NSMs may exhibit
large particle size (>100 nm) when they combine with other
materials (like polymers, biomolecules, other NSMs, etc.)
to form composite NSM or when they exist in the form of
aggregates (Bhushan, 2010). NSMs are broadly classified into
three categories, which are further classified into different
sub-categories ( Figure 1i ). The inorganic NSMs include
nanosheets (a 2-D nanostructure whose thickness lies in the
nano range), metal and metal oxide nanoparticle (particles whose
diameter is usually <100 nm), nanoshells (typically, spherical
nanoparticles with a dielectric core enclosed inside thin metallic
shell), nanowires (wire exhibiting diameter/thickness of few
nanometers), nanocrystals (material composed of atoms aligned
in single- or poly-crystalline arrangement with its one dimension
usually <100 nm), quantum dots (3-D nanocrystals composed
of semiconducting material with their diameter lying in 2–10 nm
range), and carbon nanotubes (cylindrical carbon nanostructures
with unusual properties). Organic NSMs comprise of dendrimers
(3-D, hyperbranched, tree-like polymeric nanostructures),
liposomes (nano-vesicles obtained from hydration of
dry phospholipids), and nano/micro capsules (material
composed of natural or synthetic polymer shells in order
to enclose different active materials, such as drugs, catalysts,
biomolecules, etc. as its core) (Dastjerdi and Montazer, 2010).
nanoparticles (ONPs), etc. have found their usage in widespread
domains of consumer products, food safety, agricultural
products, crop protection, and industrial processes (waste
water treatment, architectural/construction material, etc.).
Such examples of NSMs along with their dimension analysis,
antimicrobial effect on test microorganisms, and potential
applications thereof has been discussed comprehensively in
Table 1. This table has been complied by including reports
published between year 2007 and 2018 explicitly. Though
there are several reports of NSMs being used in commercial
products, however, their exact nano-formulation is not disclosed
anywhere, most likely due to trade-secret constraints. Some of
the commercial examples of aNSM based products are nasiol ©R
AntiMoss protection, nasiol ©R^ HomeWood protection (https://
nasiolgulf.com/), I-canNano metal paints, and I-canNano fillers
(https://www.icannanopaints.com/), NanoSealTM^ NanoPack
(Duncan, 2011 ), 4Care Lenscare nano-Behälter, Acticoat
Antibacterial barrier, JR Nanotech SoleFreshT nanosilver socks,
and Miradent Miradent gelée toothpaste and mouth wash
(Wijnhoven et al., 2010). Following section exclusively deals with
applications of aNSMs in aforementioned domains.
Metal/Metal Oxide Nanoparticles
Amongst different types of metal nanoparticles (MNPs), AgNPs
have witnessed their usage at much wider scale. Currently,
they have been used in more than 100 consumer products
for imparting antimicrobial effect, starting from storage wares,
textiles, nutritional additives to kitchen appliance surface
coatings, hospital consumables and wares, etc. (Li et al., 2008).
The mechanism behind their microbicidal action is mostly
accredited to release of Ag+^ ions, cell membrane or cell wall
damage, disruption of electron transport and signal transduction
pathway, and damage to cellular DNA and proteins due to ROS
(Dakal et al., 2016; Qayyum et al., 2017). AuNPs are one of the
most valuable antibacterial agents due to their biocompatibility,
higher potential of functionalization, and ease of detection. The
mechanism behind antibacterial effect of AuNP is not yet fully
explored; however, there have been reports of bacterial damage
due to modification in membrane potential, loss of ATPs (Cui
et al., 2012; Abdel-Raouf et al., 2017), and ROS generation (Zheng
et al., 2017). Like other MNPs, copper nanoparticles (CuNPs)
have also shown excellent antimicrobial activity and changes in
the morphology of microbial cell is suggested to be the plausible
cause of their biocidal action (Bogdanovi´c et al., 2014). Other
examples of antimicrobial MNPs are incorporated in Table 1.
Iron oxide has long been known for its application in the
biomedical sector due to its biocompatibility and magnetic
property. However, analysis of antibacterial property of reduced
iron (Fe^0 ) and iron oxide nanoparticles (FeO-NPs) is relatively
new. The bactericidal effect of FeO-NPs is observed either due
to disruption of cell membrane, or oxidative stress inside the
cell, or both (Lee et al., 2008; Arokiyaraj et al., 2013) or due
to oxidation of protein and peroxidation of membrane lipids
(Dinali et al., 2017). Compatibility of ZnO-NPs with human
skin and their safety has made them appropriate additive for
cosmetics, fabrics, and surfaces that remain in close proximity
of human body (Dizaj et al., 2014). Owing to their microbicidal
effect on both Gram positive and Gram negative bacteria, ZnO
nanocomposites have been applied in food packing applications
(Espitia et al., 2012). The probable mechanisms behind their
antimicrobial action are the generation of ROS, the release of
Zn ions, and the cell membrane dysfunction (Dizaj et al., 2014).
Copper oxide nanoparticles (CuO-NPs) have been exploited for
widespread applications, such as gas sensing, batteries, catalysis,
etc. In recent past, CuO-NPs were studied for their antimicrobial
property and were reported to possess excellent bactericidal and
fungicidal activity (Ren et al., 2009). Changes in surface and
morphology of microbial cell are supposedly the plausible cause
of their biocidal action. TiO 2 -NPs alone and in conjugation with
non-toxic polymers exhibit spectacular antimicrobial property.
Due to high refractive index and whiteness property TiO 2 -
NPs (especially anatase form) have been used in a varied range
of consumer merchandises, such as sunscreen lotions, paints,
cement, coatings, and toothpaste (Weir et al., 2012). They have
also been studied for their potential of potable water disinfection
as they are inexpensive, significantly stable in water, nontoxic
after ingestion, and result in photocatalytic disinfection (Li et al.,
2008 ). The bactericidal effect of TiO 2 -NPs is strongly related to
the formation of ROS, particularly—OH free radicals.
Fullerenes, Graphene, and Carbon Nanotubes
Not many reports exist on the mode of antimicrobial action of
fullerenes (C 60 ) and their derivatives thus, it would not be wise
to propose their plausible applications. C 60 and their certain
derivatives have shown strong bactericidal activity; however, no
such effect is evident in case of fullerols but they have shown
virucidal activity. The antimicrobial effect of C 60 and fullerol
is attributed to ROS independent oxidation and formation of
highly reactive singlet oxygen species, respectively. The ability
of encapsulated fullerene to show antimicrobial effects in water
(Lyon et al., 2006) can be used to solve waste water problems.
Lately, owing to exclusive surface properties, graphene-based
materials like oxides, reduced oxides (rGO), and nanocomposites
have caught researchers’ attention for their ability to act as
antimicrobial agent (Zhu et al., 2017; Jilani et al., 2018 );
however, only limited number of reports are available in this
regard. The mechanism behind their microbicidal activity is
mostly accredited to “sheet effect” (Ocsoy et al., 2017), cell
membrane dysfunction, and oxidative stress inside the cell (Liu
et al., 2011). Depending on their ability to prevent microbial
contamination, graphene-based materials have potential to be
used in food packaging. Like other aforementioned NSMs, single-
walled nanotubes (SWNTs) have also displayed bactericidal
activity against both Gram-positive and Gram-negative bacteria,
but not much work has been done in this direction. The
recognized mode of microbial toxicity behind SWNTs is believed
to be either oxidative stress that aborts integrity of cell membrane
or their adhesion onto the microbial surface (Dizaj et al., 2014).
CNTs have also been used in filters and incorporated into hollow
fibers to inhibit bio-fouling of surfaces and formation of biofilms
(Li et al., 2008). In addition, they have also been studied for their
application as construction material to impart crucial benefits
TABLE 1 |
Different nanostructured materials and composites with their antimicrobial effect against selected strains and potential applications in different fields.
Nanostructured materials andcomposites
Size/diameter
(nm)
Test microbial organisms
Effect of nanostructured material
Potential industrial applications
References
ZnO nano needle
ca. 63
Escherichia coli, Bacillus subtilis, and
Aspergillus niger
Successful inhibition of test microbes wasobserved
Functional building material
Singh et al., 2018
Nano-liposomal formulation ofmupirocin
NR
Neisseria gonorrhoeae
Highly efficacious antibacterial activity wasobserved
Next generation antibiotics
Cern et al., 2018
Chitosan (CS) functionalizedpolyaniline-polypyrrole copolymer
E. coli and E. agglomerans
Excellent antimicrobial activity againstbacterial strains
Biomedical devices, water filters, andinstrument preparation
Kumar et al., 2017
Graphene oxide-chitosan (CS-GO)nanocomposite
NR
E. coli and B. subtilis
Efficient bacterial inactivation wasobserved
Food packaging
Grande et al., 2017
Polypyrole/Cu-doped ZnOnanocomposite
E. coli and B. subtilis
Successful inhibition of test microbes wasobserved
Environmental pollution monitoring
Khan et al., 2017
ZnO-NP coated cotton composites
E. coli, S. aureus, C. albicans,and Microsporum canis
Successful inhibition of test microbes wasobserved
Textile industry
El-Nahhal et al., 2017
Fe
O 2
-NPs 3
Bacillus cereus and Klebsiellapneumonia
High antibacterial activity was evident
Antimicrobial and biomedical applications
Ansari et al., 2017
AgNPs
E. coli, B. subtilis, S. cerevisiae,and C. albicans
Highest sensitivity was evident for
E. coli,
S. cerevisiae, and C. albicans
Textile industry
Khatoon et al., 2017
ZnO-ZnS@polyaniline nanocomposite
NR
E. coli
High antibacterial activity was evident
Waste water treatment
Anjum et al., 2017
AgNPs
E. coli and S. aureus
Diminished bacterial growth was evident
Portable water filters, medical devices,food packaging, clothing, washingmachine and refrigerator coating, andstorage containers
Andrade et al., 2016
AgNPs
Candida albicans
Successful inhibition of growth of
C.
albicans
Antifungal medication against urinary tractinfection (UTI)
Oves et al., 2016
Hydroxyapatite—AgNP composite
NR
E. coli and S. aureus
Effective inhibition of bacterial strains evenat low concentrations of AgNPs
Medical implants and dental applications
Andrade et al., 2016
Cobalt doped ZnO-NP
Shigella dysenteriae, Salmonellatyphi, Vibrio cholerae and E. coli
Effective bactericidal effect against
Vibrio
cholerae and E. coli was observed
Waste water treatment
Oves et al., 2015
PEGylated Ag- Graphene quantumdots (GQDs) nanocomposite
NR
P. aeruginosa
and
S. aureus
Synergistic antibacterial effect of AgNPand GQD was observed
Next generation antibiotics
Habiba et al., 2015
AuNP stabilized liposome
NR
S. aureus
Successful antibacterial action was evident
Antibacterial agent and Drug delivery
Gao et al., 2014
(GQD)
–^67
Methicillin-resistant
S. aureus
and E. coli
Selective antibacterial photodynamiceffect of GQD was evident
Next generation antibiotics
Ristic et al., 2014
AgNP-graphene oxide (GO)Nano-sheets composite
S. aureus
and
B. subtilis
Nanocomposite resulted in complete lossof bacterial stains
Next generation antibiotics
Das et al., 2013
AuNPs
–^75
Puccinia graminis tritci, A. flavus,A. niger
and
C. albicans
Effective inhibition of test fungal strainswas evident
Antifungal medication
Jayaseelan et al., 2013
AgNPs wrapped in carbon (GO)nano-scrolls (composite)
C. albicans
and
C. tropicalis
Prolonged and enhanced antifungalactivity was evident for nano-scrolls
Next generation antibiotics, medical, andhealth care products
Li et al., 2013
CuNP
C. albicans
Strong antifungal activity was evident
Dental materials
Usman et al., 2013
ZnO-NP
25 and 40
S. aureus, S. marcescens,
and
P.
mirabilis
Prominent inhibition of the bacterial strains
Antimicrobial creams, lotions andointments, sunscreen lotions, deodorants,ceramics, and self-cleaning glass
Gunalan et al., 2012
(Continued)
like mechanical durability, crack prevention, biocidal activity, etc.
(Lee et al., 2010).
Nanoscale Chitosan (NCH)
NCH as an antimicrobial agent has strong potential for
potable water disinfection across membranes or water storage
tank surface coatings. Owing to its strong, broad-spectrum
microbicidal action and innocuous effect on vertebrate animals,
NCH has superseded other disinfectants (Beyth et al., 2015).
In recent years, NCH has found its application not only in
healthcare and consumer merchandises but also in agriculture
and biomedical products (bone cement and wound dressing
material), food packaging, waste water treatment, etc. (Li et al.,
2008 ). The exact mechanism behind its microbial toxicity is not
very clear; however, loss of cell wall integrity and consequent
alteration in membrane permeability has been reported by Kong
et al. (2008). Also, electrostatic attraction amid polycationic
chitosan and anionic bacterial cell membrane in some cases is
known to neutralize and eventually reverse the bacterial cell
surface charge. Loss of semi-permeability of the membrane has
been suggested to cause intracellular components leakage and
ultimately cell death (Kong et al., 2010; Wassel and Khattab,
Organic Nanoparticles
Although a wide range of antimicrobial drugs is available which
can efficiently kill or hamper microbial growth, however, their
ineffective and inefficient delivery to the target may result in
the poor therapeutic index and cause several local and systemic
side effects. In last few years, antimicrobial drugs encapsulated
in ONP systems have appeared as path-breaking and promising
alternatives that have not only increased therapeutic index but
also reduced detrimental side effects of the drug (Yang et al.,
2009; Nath and Banerjee, 2013). Currently, liposome is one of
the most commonly used antimicrobial drug delivery system
because it can mimic the microbial cell membrane and easily fuse
with the pathogenic microbe (Pushparaj Selvadoss et al., 2017).
Owing to the unhindered fusion of microbial cell membrane and
liposome, cargos (drugs) easily get released inside the microbial
cell and eventually result in its death (Walsh et al., 2001; Yang
et al., 2009). Polymeric nanoparticles (PNPs) have also been
extensively studied for their potential to deliver wide variety
of antimicrobial agents, as they offer numerous unique features
like stable structure, narrow size distribution, zeta potential,
ability to finely tune drug release profile, etc. (Cheng et al., 2007;
Gu et al., 2008). Like PNPs, dendrimers also possess several
exceptional properties, such as large surface area, high in vivo
reactivity, and ability to load both polar and non-polar agents,
which make them a suitable nano-platform for microbicidal drug
delivery (Zhang et al., 2010). Not only this, dendrimer itself
can act as a powerful microbicide by using the antimicrobial
agent as an elementary unit and the plausible mode of microbial
toxicity is accredited to the polycationic structural feature which
facilitates its adsorption onto the negatively charged bacterial cell.
Once adsorbed, increased membrane permeability is witnessed
that ensures entry of more dendrimers inside the cell which
later facilitate K+^ ions leakage and complete loss of bacterial
membrane integrity (Chen and Cooper, 2002; Ladd et al., 2017).
The detailed discussion on antimicrobial activity of dendrimers
has been described elsewhere (Scorciapino et al., 2017).
LIMITATIONS OF PRESENT WORK AND FUTURE PROSPECTS OF aNSMs
The exact mechanism behind antimicrobial effects of NSMs still
remains unclear. Certain reports recognize ROS generation or
development of oxidative stress as a cause of microbicidal effect,
while others suggest antimicrobial effect cannot be associated
with metabolism regulation (Dakal et al., 2016). Therefore,
addressing exact mechanism behind the antimicrobial action of
NSMs should be considered in future work. Several microbes
present complex cell membrane structure, therefore, the in vitro
models cannot completely mimic the in vivo conditions to
accurately study the effect of aNSMs in duplicate real systems.
Other limitations of the current works include lack of unified
standards to compare antimicrobial effects of NSMs in order to
ensure their potency as antimicrobial agent. Application of NSMs
in waste water treatment has raised serious health concerns due
to their aggregation in water. Further, loss of nanoparticles during
downstream processing may cause toxicity in human beings
and affect different ecosystems, therefore future work should be
directed toward developing better technologies for retention of
nanomaterials. Also, cost effective NSMs should be looked for
the disinfection purpose in order to compete with conventional
disinfectants.
CONCLUSIONS
Owing to their spectacular properties, NSMs in both organic
and inorganic forms have engendered several interesting fields
in science and technology. Incessant investigation for their
application has led to the development of practical productions
and commercialization of products in some cases. Considering
the current scenario of human health, its comfort, and well-
being; NSMs have been welcomed open-heartedly by several
industries, such as health and personal care industry, textile
industry, environmental industry, etc. However, realizing the
application of NSMs at large scale in the economic setup is still
a long shot. Therefore, future work should be directed toward
designing novel, applicable, and inexpensive methodologies for
scaled up manufacturing of these NSMs in order to meet the
growing human needs.
AUTHOR CONTRIBUTIONS
AB and PC: wrote the manuscript; AS: helped in writing; PK,
PM, and VB: edited the manuscript. All authors proofread and
finalized the manuscript.
ACKNOWLEDGMENTS
This work is supported by DST Ramanujan Fellowship
(SB/S2/RJN-042/2015) awarded to PC by Government of India.
AS thanks Dr. U. S. N. Murty, Director NIPER- Guwahati for his
support and encouragement.
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Conflict of Interest Statement: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
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