Surface Modification and Application of Nanomaterials in Biotechnology-Juniper Publishers
Authored
by Hélio Ribeiro
Abstract
In the last years, inorganic nanostructures as carbon
nanotubes, graphene, hexagonal boron nitride, and metallic
nanoparticles have been applied in several biomedical and nanotechnology
fields. These different types of nanomaterials also are awakened as new
perspectives in prophylactic, diagnostic and therapeutic areas.
However, the uses depends strongly on their chemical and physical
surfaces that display an important role in their biocompatibility in
different biological systems. A brief study of several types of
nanomaterials, their modifications and biomedical application is the
main contribution of this short communication.
Keywords: Nanotechnology; Nanomedicine; Nanomaterials; Carbon nanotubes; Graphene; Hexagonal boron nitride; Gold nanoparticles
Abbreviations:
CNMs: Carbon Nanomaterials; h-BN: Hexagonal Boron Nitride; CNTs: Carbon
Nanotubes; rGO: Reduced Graphene Oxide; Dox: Doxorubicin; PEG:
Polyethylene Glycol; BNNTs: Boron Nitride Nanotubes; MDS: Molecular
Dynamics Simulations
Introduction
Many studies about nanomaterials have been widely
explored in recent decades in different scientific and technological
areas. Several authors consider that the discovery of CNTs by Iijima [1]
and graphene by Geim and Novoselov [2], stimulated the studies in
nanotechnology. Concomitantly, the advances in probe, scanning, and
transmission microscopies, it has also contributed to the discovery of
new nanostructures and the understanding of others that were not yet
well elucidated. It was expected exceptional physico-chemical properties
and biocompatibility of nanostructures such as CNTs, graphene, h-BN,
BNNTs and metallic nanoparticles, among others [3]. On the one hand,
these materials have an enormous potential range of applications in
nanotechnology, bioengineering and biomedicine [4,5], such as tumor
markers[6], drugs delivers [7], bio-packaging [8], biosensing [9-11],
adjuvant in vaccines [5-12,13], among others. However, the compatibility
and dispersion of these nanoparticles in the medium of interest are
fundamental to their potential applications [3]. The nanoengineering
interfaces between host biological system and nanoparticles involves
several challenges that need to be overcome. For instance,
there-stacking or agglomeration processes of nanoparticles do not allow
them to transfer their expected properties to the system, resulting in
an inhomogeneous dispersion medium with minimum of biocompatibility.
These undesirable processes can be overcome
by physical or chemical modification methodologies of their surfaces,
such as covalent or non-covalent functionalization. Thus, our choices
will depend on the nanoparticles and the biological system in study. The
covalent functionalization depends on bonding between the nanoparticles
and the functional groups that were chosen, according to the
selectivity [3]. Based on this approach, different organic or inorganic
functional groups or nanoparticles can be anchored. For instance, it can
be introduced on surfaces of oxidized CNTs or graphene oxide (GO),
functional groups such as alkoxy (-OR), amino (-NH2), amine
(-NHR), alkyl (-R) [14,15], heteroatom doping, metallic nanoparticles,
biomolecules and biopolymers, among others. These modifications process
alter significantly their interactions with the medium leading them to a
large range of solubility in water, co-polymers or organic solvents
[3]. On the other hand, non-covalent functionalization processes of
nanoparticles are strongly dependent of their physical interaction with
host system through intermolecular forces, such as van der Waals,
hydrophilic, hydrophobic, hydrogen bonding and π-π interactions, among
others [16]. Taking advantages of these physical interactions of
molecules (conjugated, surfactants etc), they form homogenously
dispersion into different medium with their controlled physicochemical
and biological properties [17].
In this context, several studies have presented different
types of covalent and non-covalent functionalization of these
nanostructures with great technological demands, such as: in
cellulose films or fibers [18,19], chitosan [20], polyethyleniminegrafted
nanoribbon (for recognition of microRNA)[11],
vinyl acetate co-polymer[17], octadecylamine [21], glucose
oxidase biosensing [22], poly(ethylene glycol) [23], DNA [24],
metallic nanoparticles, among others. Some examples of these
modifications in CNMs can be seen in Figure 1a-1d.
Large amount of nanostructures, zwitterions, supra
molecular, clusters, including micelles, dendrimers, quantum
dots, biopolymers CNTs, graphene, metallic nanoparticles, have
been intensively investigated as biological agents in several
biotechnological applications [25]. For instance, gold nano
spheres and gold nanorods (Figure 2a-b), have represented
the most attractive metallic nanostructures for biological
application due to their biochemical features and low related
toxicity. Gold nanorods biosensing is the modality widely used
especially for the development of optical and electrochemical
sensing platforms. The surface plasm resonance properties
based on their sensitive spectral response in light absorption and scattering can change in the biological environment,
allowing the monitoring of light signal, for instance in cancer
cells[26]. One the most important gold nanoparticle application
is in vaccine development [26]. There is a great evidence that
these nanoparticles display adjuvant characteristics, promoting
cell recruitment, antigen-presenting cell activation, cytokine
production, and inducing a tumoral immune response [12].
Another relevant application based on physical properties of
gold nanorods is their enhanced optical absorption in the visible
and NIR region that has been proposed as an alternative for the
localized ablation of target cancer cells without damaging other
healthy cells, this technique is known as photothermal therapy
[6]. Regarding the development of new strategies for cancer
therapy, gold nanoparticles have shown promising perspectives
to increase radiation effects mainly in tumor cells rather
than in normal cells. This effect is due to the high Au atomic
number that can lead to increased cross section probability
under photons beams from ionizing radiation sources [27].
Nonetheless, gold nanoparticles present relative easy surface
functionalization and several biological molecules currently
used as immunotherapeutic, such as cetuximab and trastuzumab
have demonstrated improved effects when associated with gold
nanoparticles [28]. There is a plenty literature about biomedical
applications of gold nanoparticles highlighting their importance
and advantages to improve diagnostic and therapies for
infectious and degenerative diseases as well as a `big deal` to the
pharmaceutical industry in a near future [29].
Other important class of nanomaterial with great potential
application in bionanotechnology are recognized as one or
bi-dimensional, such as CNTs, BNNTs, graphene, h-BN,among
others. These nanostructures present exceptional physical
properties, besides good chemical stability, well-tailored
biocompatibility and lower cytotoxicity [21,22,30]. For example,
BNNTs and CNTs are tubular nanostructures with large aspect
ratio, high mechanical strengths, and they have a potential
application as nanocarriers for use as cancer drugs [25]. Weng
et al., [21] demonstrated that the BNNTs functionalized with
hydroxyl groups loaded ~300wt% of doxorubicin (Dox), a
monoclonal antibody for targeting and a fluorescence marker
for visualization, with application in cancer therapy [31], this
nanocomplex exhibited higher efficiency to reducing LNCaP
prostate cancer cellular viability than the free drug alone [21].
CNTs also can be used as carrier for drug delivery when they
are tailored at entering the cells nuclei. Researches have showed
that functionalized CNTs can cross the cell membrane, without
cellular recognition as harmful intrudes [32]. In other studies,
it was demonstrated that the Dox interacted with CNTs through
π-π stacking following the functionalization with polyethylene
glycol (PEG) to increase their blood circulation plasmatic halflife
and to decrease their toxicity [33]. Likewise, CNTs samples,
were modified with Dox, and the results showed that cancer cells
efficiently took up this compound. While Dox was effectively
released and accumulated in the nucleus, while CNTs remained
in the cytoplasm.
This result indicates the high loading capacity of the CNTs
due to its large aspect ratio and effective noncovalent interaction
between them and drug molecules [25]. Gao et al. [19] showed
by MDS studies that, DNA molecule in water environment can be
inserted into CNTs (endohedral functionalization) through van
der Waals and hydrophobic interactions. Based on their studies,
they suggested that the encapsulated CNTs-DNA molecular
complex can be used as DNA-modulated molecular electronics,
biosensors, DNA sequencing, and gene delivery systems [32,34].
Zheng et al. [24] proposed an effective technique of dispersion of
CNTs in water by their sonication process in presence of DNA. By
MDS this research group suggested that DNA can binds to carbon
nanotubes through π-stacking, resulting in helical wrapping in
their surface[24] (Figure 1a).
Conclusion
In this short communication we highlight some experimental and theoretical works with different combinations of nanostructures and molecules, as well as metallic nanoparticles with potential bio and technological applications. However, the most important aspect for success and an optimal performance of these compounds is the choice of the best tailored functionalization process (bio-nano engineering) for each type of biological system. The physical-chemical modification is an essential step for relevant applications, leading to hybrid compounds chemically stable, tailored, well dispersed, and compatible with the biological environment of interest. Thus, it is possible to produce smart nano-systems with advanced applications in biotechnology and biomedical areas, such as ecological packaging, bio-robots, biosensors, adjutancy in vaccines and tumor markers for diagnosis and therapy.
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