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Файл:Ординатура / Хирургия / Библиотека им академика М.И. Перельмана / Книга_5604_Библиотеки_им_академика_М_И_Перельмана.pdf
Carbon-Based Nanostructured Materials: Designing … 55
Fig. 7 Applications of CNM in agriculture, industry, and environmental protection
5 Applications of Carbon-Based Nanostructured Materials
5.1 Agricultural and Industrial Applications
and Environmental Protection
Carbon nanocomposites are very attractive due to their better performance for the
treatment of contaminated environments, whether aqueous or in soil, for use in agriculture for detection of pesticides, or as biofertilizers, for pest control, as well as
the use of in different energy, metallurgical, and food industries among others [46].
Figure 7 schematizes the different applications of carbon materials in agriculture and
industry, as well as in environmental protection.
5.2 Antibacterial and Antiviral Applications
Carbon-based nanomaterials are good antibacterial, antifungal, and antiviral candidates due to their physical properties. The general mechanism by which they act is
through physical damage to the plasma membrane cell wall-generated pores, oxygen
reactive species (ROS) production, and oxidative stress, which can cause damage to
structures such as DNA. Also, CNMs interact through positive charges with positive
loads of viruses, causing physical harm to their system. Another way of acting is
the transport, delivery, and potentializing of antimicrobials. Table 2 summarizes the
antimicrobial and antiviral activity of carbon nanocomposites.
56 V. Esparza-Cordero et al.
Ta bl e 2 Antimicrobial and antiviral activity of carbon nanocomposites
Carbon-based
nanocomposite
Graphene E. coli,
Oxide of
graphene
Graphene
quantum dots
(GQD)
Fullerenes Escherichiacoli Photoactive platform [64]
Nanotubes Methylobacterium spp.
Antimicrobial activity/
antiviral activity
S. aureus
Respiratory syncytial
virus (RSV)
Wine epidemic diarrhea
virus (ARN virus)
DNA pseudorabies
virus (ADN virus)
Herpes simplex virus
type 1, HSV-1 (human
alphaherpesvirus 1)
Entericvirus, H9N2.
EV71 responsible for
diseases of the hands,
feet, and mouth
Fusarium graminearum
(FG)
Candida albicans
Saccharomyces
cerevisiae
Herpes simplex virus
type 1 (HSV-1)
Immunodeficiency
virus HIV-1
Human coronavirus
HCoV-229E
Methicillin-resistant S.
aureus (MRSA)
and E. coli
Immunodeficiency
virus HIV-1
Sphingomonas spp.
K. pneumoniae, P.
aeruginosa, E. coli,
B. subtilis
Mechanism of action References
Direct contact with the membrane,
which causes pores and generates
oxidative stress
Functionalized with sulfonate and
β-cyclodextrin loaded with curcumin
compound (GSCC)
Physical alteration in the structure of
the virus due to the sharp edges it
presents
Affect the synthesis of the micellar
cell wall
Interfering with the interaction
between cells receptors and the virus
Functionalized with –NH2and –NH
they show adhesion to the bacterial
cell membrane
Blocking HIV protease [55, 59, 65]
Functionalization with surface
functional groups and synergy with
AgNPs
Nitrogen-fluorine-boron-phosphorus
doped
Antibiofilm
[55]
[45]
[59]
[46, 61]
[59, 62]
[63]
[60, 66]
Carbon-Based Nanostructured Materials: Designing … 57
5.3 Theragnostic
Theragnostic is the combination and interaction of therapy and diagnosis and is
widely used in diseases such as cancer. Carbon-based nanocomposites help not
only in the diagnosis but also in the location and identification of the stage of the
disease, which provides the necessary information to improve adequate treatment,
also considering that these nanocomposites can transport a therapeutic agent directly
to the tumor [67]. Tumor therapy by nanocomposites carbon depends on the internalization of suppressive drugs or photodynamic therapy (PDT) and photothermal
therapy (PTT) agents in the target area to inhibit or even destroy tumors [68].
5.3.1 Photodynamic Therapy (PDT) and Photothermal Therapy (PTT)
Nanocarbon compounds have been used in photodynamic therapy; the therapy
consists of the absorption of photosensitizer in the target tissue, activation by a
specific wavelength, which generates ROS, which triggers tumor cell death, the use
of CNM has a target on cancer cells, preventing the absorption of these nanocomposites by healthy cells. Among them are fullerenes, as they have presented visible light
absorption combined with efficient cross-system crossing to a long-lasting triple state
that causes fullerenes to generate ROS after illumination and allows fullerenes to act
as photosensitizers [42, 47, 65, 69]. CD quantum carbon dots are used and modified for photothermal therapy (PTT) since they have a high photothermal conversion
efficiency (low laser irradiation), generating a temperature increase. Compared to
inorganic agents for PTT, they require high absorption to convert light into heat and
generate thermal ablation of cancer cells, in addition to observing that the greater CDs
present more excellent biocompatibility compared to that of the agent’s inorganic
PTTs [68]. Single-walled carbon nanohorns (SWNHs) coated with indocyanine green
(ICG) were developed, where it is observed that it has thermal properties and the
generation of ROS under near-infrared (NIR) laser irradiation, showing the effective
elimination of 4T1 cells from triple-negative breast cancer [70].
This therapy also has antimicrobial effects since it has been observed that CNM
binds to the microbial cell, destroying the microorganisms by initiating an exothermic
reaction in NIR laser irradiation [56]. Carbon quantum dots (CDs) coated with
curcumin, when irradiated with a wavelength of 416 nm, generate singlet oxygen;
in the same way, at an irradiation lower than 808 nm, it presents photothermal property, which generates photoinactivation of microorganisms such as S. aureus and E.
coli [71]. Fullerenes (C
of singlet oxygen, generating the destruction of multidrug-resistant Staphylococcus
aureus in an infected mouse wound under light irradiation [47].
-PTC) present a photodynamic property through the release
60
58 V. Esparza-Cordero et al.
(a) (b)
Fig. 8 a General mechanism of photodynamic therapy and b General mechanism of photothermal
therapy
5.3.2 Cancer Therapy
The use of SWCNH has been observed as an inducer of apoptosis in cancer cells
due to the production of oxidative stress, as well as inhibitors of cell proliferation
in a dose-dependent manner [56]. For its part, fullerene has photodynamic capabilities, synthesized a heavy atom-free photosensitizer that can be activated by pH
by introducing a fullerene unit in rhodamine B and nanoparticles (C
-RB NPs).
60
Demonstrating the capacity for cellular uptake, lysosomal activation at acidic pH
fluorescence turn-on, and efficient generation of singlet oxygen, which might be
a candidate for the identification and therapy of cancer [47]. In 2018, Flak and
Przysiecka [72] synthesize graphene quantum dots (GQDs-MSNs) as a fluorescent
agent, immobilized on mesoporous silica nanoparticles and loaded with doxorubicin,
demonstrating its ability to penetrate, label, and deliver the drug to the target cell,
Fig. 8.
Various studies show the use of carbon nanotubes for the diagnosis and treatment
of melanoma [73], as well as for the treatment of colorectal cancer, in preclinical trials
where carbon nanotubes will be observed due to their competent charge, surface area,
and stability; improved biocompatibility and targeted drug release make CNTs an
innovative option for drug delivery [74]; and another study shows that single-walled
carbon nanotubes (SCNTs) and multi-walled carbon nanotubes (MWCNT), coated
with peptide lipids (PL) and sucrose laurate (SL), showed high tumor inhibition [63].
5.3.3 Imaging Biomarkers for Diagnosis
Carbon nanomaterials have been used in the development of new optoelectronics,
devices,and the bioimaging field by leveragingits physicochemical properties, which
include high biocompatibility, high quantum performance, adjustable fluorescence
Carbon-Based Nanostructured Materials: Designing … 59
properties, and reduced nanoparticle diameter [75]. Due to the absorption spectrum
in the visible and NIR and the fluorescence capacity, CNMs are good candidates for
biological imaging detection.
CDs present emission near 700 nm, a characteristic that allows them to be used
for medical applications, unlike conventional organic dyes, a very desirable characteristic due to the low absorption of the tissue and the reduced dispersion of light,
which makes it an excellent candidate for use in image detection, so they are luminescent nanomaterials. It has been observed that they can be used as in vivo imaging
probes since biomolecules are transparent to NIR radiation; CDs are modified to
detect biomarkers present in the plasma membrane, cytoplasm, or even in cancer cell
DNA. The use of CDs functionalized with proteins such as enzymes or antibody and
labels has been used to diagnose tumor cells through the emission of fluorescence in
various cancers such as ovarian cancer, melanoma cancer, or a glioma [42, 68].
The fluorescence generated by SWCNTs excited in the NIR-I (700–900 nm) and
NIR-II (1100–1400 nm) ranges for the observation of blood vessels [57]. HepG2
liver carcinoma cancer cells have also been labeled with C
-TEG and C70-
60
TEG, observing fluorescence images, Fig. 9 [45]. NDs are emerging as a promising
candidate mainly for their photostability and biocompatibility in various cell lines
(in vitro). Even with fewer animal models (in vivo), NDs cannot alter the cellular
metabolism and remain a non-toxic marker at low concentrations. Most CNOs are
not fluorescent and cannot be used for bioimaging applications. Therefore, to make
them emissive, green/red/NIR emitter tints have joined CNO through covalent/noncovalent interaction. Studies have found that images of Drosophila melanogaster
have been obtained and that they have been found to cross the hematoencephalic
barrier by matching the use to obtain images of Escherichia coli [42, 58].
Fig. 9 Image diagnosis from CNM
60 V. Esparza-Cordero et al.
5.4 Wound Healing
Carbon-based nanomaterials (CMNs), such as GO (flat form—2D), reduced
graphene (rGR, flat shape—2D), CNT (tubular form—1D), and fullerene (C
ical form—0D) can be used in wound healing applications [76, 77]. Manufactured
a stack consisting of curcumin and Gymnema Sylvestre incorporated a compound
of graphene-polyhydroxybutyrate-sodium alginate (GO-PHB-SACUR&GS) as an
extracellular matrix platform for wound healing, where they observed increasing
the cellular viability of both wounded cells and diabetic wounds without producing
cytotoxic effects and improving wound closure [42] covered GO nanosheets over
structurally covered nanofibrous platforms (chitosan, CS) and nucleus (Lpolylactic
acid, PLLA), observing their antimicrobial capacity as well as the proliferation of pig
endothelial cells. Bioactive glass (BG) functionalized with graphene oxide showed
its anti-inflammatory effect and improved wound healing properties [78]; in another
study, GO/Cu/chitosan/hyaluronic acid after points were created which were used in
a murine model where wounds were healing, as well as angiogenesis during healing
prices were favored [42]. In the development of a hybrid structure of graphene/
plate/arginine oxide (GO/Ag/Arg) after 12 days of application on wounds in mice, a
significant increase was observed in the healing process and the reconstruction of a
thickened layer of epidermis on the surface of the wound [60, 76].
Carbon/chitosan/isoniazid nanotubes promoted the healing of tuberculosis ulcers
3+
observing a decrease in the number of CD
and CD4+T cells. This nanocomposite is a pharmacological candidate for secondary bone tubercle wound healing
[79, 80]. Synthesized SWCNTs and MWCNT’s with chitosan, they observed reephitelization of wounds in mice; however,theyalso increased the percentage of wounds
with more significant fibrosis. At the same time, heteroatoms (N, F, P/B) have been
developed in corporate multiple-walled carbon nanotubes (MWCNTs), where they
examined the healing ability through wound reepithelization in Wistar rats [66].
Hydrogel patches covered with hyaluronic acid (HA) and CNT spikes have been
manufactured, and it has been demonstrated that they accelerate tissue regeneration of
wounds [81]. The construction of nanotube-based collagen pads has shown complete
reepithelization and a more significant collagen deposition than other groups treated
with pads [76]. Quantum points positivelycharged CQD (PC-CQDs), used as antimicrobials and as well as to treat wounds, through a murine experiment, observed
that after nanomaterial exposure to passing days, there was a decrease in the presence of white blood cells compared to wound control, and PCR levels, decreasing
inflammation, and favoring recovery from infected wounds, Fig. 10.
, spher-
60
5.5 Tissue Engineering
CNMs have the property of stimulating precursor cells; this characteristic gives
them the ability to be used as platforms for tissue engineering as well as for repair
Carbon-Based Nanostructured Materials: Designing … 61
Fig. 10 Wound healing by CNM
[82], CNTs are an excellent alternative as substrates or additives in biomaterials for
tissue regeneration due to their mechanical and electrical properties, they help the
regeneration and proliferation of cardiomyocytes [83], likewise carboxyl-modified
multi-walled carbon nanotubes (mMWCNT) were introduced into alginate scaffolds
sodium/gelatin (Alg/Gel) to optimize the function of the hybrid scaffolds, achieving
cell proliferation and neurite outgrowth under electromagnetic stimulation [74].
PC
12
Functionalized multi-walled carbon nanotubes (FMWCNT) could form a fibrous
scaffold, modified with the electrospinning technique, which is like polyurethane
and silk fibroin. These were used for neuronal growth and differentiation due to their
properties. They significantly stimulated the growth and proliferation of Schwann
cells (S42), along with the distinction and spontaneous growth of neurons in rats
[84]. Graphene has been used as a candidate for the stimulation of cell proliferation in various tissues; within the areas of study, its potential in neurogenesis and
osteogenesis has been observed in Fig. 11 [85].
CQD has been functionalized with p-phenylenediamine (modify-CQD), in which,
when used for cardiac tissue, the proliferation of cardiomyocytes is observed as
the influence increases in the expression of cardiac markers [86]. Carboxymethyl
Fig. 11 CNM scaffolds for cell proliferation in tissue engineering
62 V. Esparza-Cordero et al.
cellulose-hydroxyapatite nanocomposite conjugated with carbon points has been
synthesized, showing osteogenic properties for bone tissue engineering [87]. Other
studies showing the ability of CDs to promote bone growth are those proposed by [67,
88] which used three-dimensional graphene foam (3DG) to stimulate the production
of metabolites, which help the proliferation of neural stem cells. Functionalization
scaffolds have been built with GO to promote the adhesion, aligned migration, and
differentiation of stem cells into supporting neuronal and glial cells [89]. Within
the stimulation of cells of the bone system, [90] synthesized scaffolds based on
bioactive glass containing graphene and bilayer based on poly (ε-caprolactone) for
the proliferation of osteoblastic and chondrogenic cells.
5.6 Drug Delivery
The administration of medications from CNM can occur through two methods: the
passive, in which, based on the hydrophobic effect, the drugs can be absorbed, and
when they are in the target cell, the drug is released. In self-administration, the
medication is directly linked to the CNM, drug orientation is of vital importance, and
is classified as active and passive. Passive orientation uses antibodies and peptides
to anchor them to the receptors of the target cells. In this orientation, the CNM
drug circulates through the bloodstream and, by affinity, is driven to the target site
depending on temperature, pH, shape, and size [42]. In nanotechnology, CNMs have
a particular focus on drug delivery applications. The advantages of CNMs are their
nanoscale size, ease of conjugating many therapeutic products, the chemistry they
can present on their surface, and their biocompatibility. For example, CNTs undergo
entry into cells through a surface receptor, while GQDs can directly enter the cell
membrane due to nanoscale [86].
Graphene derivatives are excellent candidates for drug administration since they
can load hydrophilic and hydrophobic drugs; this is due to their ultra-high surface
area and high mechanical resistance. Being easy to functionalize, it also presents a
targeted and localized administration of drugs without losing its effectiveness [91].
In the administration of drugs, it has been possible to functionalize on the surface of
GO through covalent conjugation or non-covalent adsorption to various drugs. This
capability is due to the p electrons dislocated in the plane of graphene that allow the
binding of aromatic drugs or molecules through π–π stacking. Chemotherapeutic
drugs have been joined, including camptothecin ( CPT) and doxorubicin (DOX),
among others [92].
For the treatment of cardiovascular diseases, it has been used as a drug in polymer
films with reduced graphene oxide (rGO) with hyaluronic acid (HA), gelatin (Gel),
poly (ethylene oxide) (PEO), loaded with irbesartan (IRB) for its administration.
Carbon dots (CDs) have been used to deliver chemotherapy drugs, as they s uffer
from water dispersion, biocompatibility problems, and side effects. An injection is
a form of binding covalent chemistry. CDs with platinum are used for metastatic
colorectal cancer [68]. On the other hand, the quantum points of graphene (QGD)
Carbon-Based Nanostructured Materials: Designing … 63
can be modified with a fluorescent agent into mesoporous silica nanoparticles and
loaded with doxorubicin, which is a pH-dependent release sample and temperature
dependent [72]. Fullerenes are used in the administration of small molecules such as
nucleic acids, as well as the targeted administration of cancer drugs through the conjugation of doxorubicin with fullerene, and this is a chemotherapeutic agent against
various types of cancer such as breast cancer, lung cancer, ovarian cancer, bladder
cancer,Hodgkin lymphoma, and leukemia. In turn, it is used for administering topical
drugs and has the potential to administer drugs in the CNS [ 65]. Patra et al. [42] study
synthesized fullerene C
functionalized with lysine using a biocompatible binder
60
followed by the bonding of a biodegradable hydrophilic binder to increase aquatic
solubility,as well as a load of Monomethyl fumarate; this is an active form of the drug
dimethyl fumarate, which induces lysis of tumor cells, preferably by the mechanisms
involving NKp
4622
.
These are also potentially appropriate drug carrier candidates within nanotubes
due to their stability, inertia, and large surface area. CNH’s potential for delivering
anti-inflammatory drugs and antibiotics has been demonstrated [56]. Multi-walled
carbon nanotubes have been covalently conjugated with levofloxacin (MWCNTLVX), generating a nanoantibiotic modified to an effective, safe, and fast-acting
with minimal side effects [33], Costa et al. [93] shows the potential of functionalized
MWNTs for treating neurodegenerative disorders since they cross the blood–brain
membrane. Likewise, SWCNH is an alternative to chemotherapies. Its functionalization enables selective drug localization at specific receptors, resulting in a slower
release of the drugs within the body while minimizing any potential damage [56].
Also, the use of carbon nanotubes and chitosan for treating tuberculosis by slowly
releasing isoniazid has been studied [94]. Nanochips, like other carbon-based nanomaterials, are candidates for anchoring, damaging, delivery, and release of components, as demonstrated by d’Amora et al. [95], achieving covalent immobilization of
a synthetic glycopeptide and bovine serum albumin protein (BSA) on the surface of
carbon nanochips and these penetrate cells through endocytosis, Fig. 12 [42].
5.7 Biosensing
A biosensor is an analytical device that analyzes a sample in the presence of a specific
analytical target. The biosensor consists of three components: a device that contains a
biological receptor for recognition, like an enzyme; a signal transducer that converts
biorecognition energy into another form; optical, electrical, thermal, and a signal
processing system, which reads and records the response analytically, Fig. 13.The
use of nanomaterials for the biosensor area is booming due to the physical and
chemical characteristics that these materials present, such as easy adsorption and
rapid transfer of electrons, high conductivity in particular directions, a large surface
area, which improves the absorbance of catalyst biomolecules, which are selective
due to their unique electronic structure, and tunable surface chemistry for species
of capture probes or analytes. These materials are ideal for biosensors that require
64 V. Esparza-Cordero et al.
Fig. 12 Carbon-based nanomaterials (CNMs) as drug deliverers
multiple layers of enzymes and provide an excellent interaction through layers and
with electrodes. Carbon nanotubes and graphene derivates can be an attractive option
for the development of cheaper, easy-to-use, and more sensitive sensors [96].
The flat 2D hexagonal structure, the graphene atoms architecture, and the movement of free electrons, which generate high electrical conductivity, as well as its
surface area and mechanical resistance, are the properties that make it. This nanocomposite is an excellent biomarker of diseases [97]. CNTs are one of the most widely
Fig. 13 General scheme of CNM-based biosensor