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Файл:Ординатура / Хирургия / Библиотека им академика М.И. Перельмана / Книга_5362_Библиотеки_им_академика_М_И_Перельмана.pdf
Carbon Nanomaterial-Incorporated Supramolecular Drug Delivery 145
3.2.3 Biomimicry
To generate fully mimetic systems for improved therapeutic efficacy, synthetic
materials must mimic biological materials’ functional or structural complexity.
Supramolecular biomaterials can mimic biological signal transmission. Amino acid
coding components used in biological signaling are already present in materials made
from protein building blocks or peptides, whether created by molecular stacking or
polymeric antecedents. Tissue engineering and regenerative medicine could benefit
from biomaterials that mimic or replace natural components or signaling pathways.
To serve as synthetic scaffolds, supramolecular biomaterials mimic fibrous matrix
components [75].
3.2.4 Dynamic Reciprocity and Responsiveness
Supramolecular substances can swiftly adapt to multiple external stimuli, mimicking
livesystem dynamics due to non-covalent interactions’ dynamic nature. Temperature,
voltage, light, magnetic field, pH, redox agent, ionic strength, and competitive hostguest interactions have been used to influence assembly. Smarter treatments can be
created by engineering supra-molecular biomaterials that can modify characteristics
in real time or autonomously sense and respond to environmental cues. Enzymes
that decide whether an oligo peptide may be stacked one-dimensionally govern
self-assembling systems with reversible enzymatic switches and protease-responsive
components. In biological systems, intricate and interconnected molecule-building
and disassembly processes are regulated by competing catalytic pathways, which are
influenced by thermodynamic and kinetic factors.
3.3 Applications of Supramolecular Biomaterials
Supramolecular biomaterials have diverse applications, such as drug delivery, engineered cell environments, and regenerative medicine. These materials play a crucial
role in drug delivery by enabling the precise release of small-molecule pharmaceuticals, enhancing the solubility of bioactive proteins, and carrying other medically
significant payloads. They possess significant value in the management of cancer.
In engineered cell circumstances, these materials function as the substrate or threedimensional bases that facilitate cell survival, activity, and phenotype control for
therapeutic population growth. Lastly, supramolecular biomaterials contribute to
advancements in regenerative medicine. Supramolecular biomaterials in each sector
enable novel therapies that are impossible using conventional biomaterial production
methods.
146 N. T. Tuli et al.
3.3.1 Drug Delivery
The structural components of supramolecular biomaterials allow for controlled drug
release. Self-assembled peptides can have drugs added as prosthetic groups through
hydrolytic couplings, allowing for controlled and prolonged drug release when hydrogenated. Hybrid peptides with aliphatic chains are efficient drug transporters because
their hydrophobic core can contain poorly soluble medications. Numerous methodologies have been devised to actively control the release rate of a chemical compound
by manipulating the stability or dynamic properties of the supramolecular links
constituting the substance.
3.3.2 Engineered Cell Microenvironments
Synthetic matrices with adaptable bioactivity, mechanics, and material shape can
be built using supramolecular principles for cell support and transport. Therapeutic
stem or progenitor cells can be fostered in an optimal environment by inverting
supramolecular interactions to generate cell scaffolds amenable to minimally invasive delivery. In this particular context, the utilization of three-dimensional matrices
composed of peptides or modified proteins has been found to possess bioactive properties and exhibit beneficial effects. Epitopes for integrin attachment are commonly
found in supramolecular biomaterials to serve as cell-adhesive cues.
3.3.3 Regenerative Medicine
Supramolecular biomaterials have been demonstrated to regenerate multiple tissues
and organs, mostly in preclinical animal models. One of the many therapeutic strategies investigated is using materials as scaffolds to promote endogenous tissue repair,
deliver soluble growth factors or medications, mimic powerful signaling proteins,
deliver therapeutic cell populations, or restore tissue functionality [1]. Because of its
limited endogenous regenerating capacity,central nervous system regeneration poses
a unique difficulty. Injectable supra-molecular peptides have been used as a strategy
for brain regeneration because of their ability to stimulate neuronal reconnection in
the aftermath of injury. In mouse models, restoring eyesight following optic nerve
amputation by encouraging axon elongation has shown encouraging results. On the
other hand, supramolecular biomaterials are being utilized as inductive substances
to promote healing processes or provide the controlled release of growth factors that
stimulate the natural regeneration of tissues [76].
3.3.4 Immuno-Engineering
Immunomodulation techniques like prophylactic vaccination or reducing inflammation and autoimmunity have recently garnered attention. Supramolecular systems
Carbon Nanomaterial-Incorporated Supramolecular Drug Delivery 147
can deliver soluble drugs and immunomodulating signals. In a chronic obstructive nephropathy model, tailored recombinant protein hydrogels delivered IL-10 to
protect against inflammation. T and B-cell epitopes can be shown via supramolecular peptide assemblages, eliciting cellular and humoral responses from the immune
system. Strong immune responses can be elicited without an adjuvant by presenting
high densities of epitopes on supramolecular peptide fibrils. The supramolecular
distribution of natively folded entire protein antigens utilizing a fibrillating domain
as a template elicits a strong immunological response.
3.3.5 Supramolecular Chemistry in Molecular Imaging
In the early 1990s, Brad Smith made significant contributions to the domains of ionpair receptors, transport through membranes, and rotaxane synthesis. Eventually, he
integrated his research in molecular imaging with his work in rotaxane synthesis
[77]. Incorporating a guest molecule into a macrocyclic host molecule, forming a
rotaxane, involves threading the guest molecule through the host molecule. This
threaded structure is subsequently sealed at both ends using certain functions to
ensure the macrocycle remains securely attached and does not detach [78].
4 Carbon Nanomaterial-Incorporated Supramolecular
Drug Delivery
4.1 Carbon Nanomaterials as Building Blocks
for Supramolecular Structures
Carbon nanotubes (CNTs) have emerged as a prominent subject of study in nanomechanics. Carbon nanotubes (CNTs) possess an atomically perfect structure, elongated
and hollow in shape, with a surface absent in single-walled nanotubes (SWNTs).
Additionally, their high covalent bond strength renders t hem exceptionally wellsuited for applications in the field of nanomechanics. The term “resilient” was initially
employed in investigating high-energy collisions involving smaller fullerene cages,
such as C
The resilient cages of fullerenes exhibited remarkable elastic deformation tolerance,
as they remained intact and undistorted despite the impact. Carbon nanotubes (CNTs)
are nanocrystals with well-defined primordial cells, transportability, surface, etc.
The stiffness, moduli, compliance, geometry, and geometric scale of engineering
structures can be studied. Nanotubes are intriguing because of their mesoscopic
size (a nanometer diameter) and homogeneous, almost translation-invariant shape
throughout micrometer lengths.
Furthermore, carbon has a remarkable capacity to construct diverse forms,
rendering it one of the most captivating components. Various allotropes of carbon
, and C84, rebounding off a diamond wall terminated with hydrogen.
60,C70
148 N. T. Tuli et al.
have been identified depending on the valence of carbon atoms, including carbon
quantum dots, zero-dimensional fullerenes, two-dimensional graphene sheets, and
one-dimensional carbon nanotubes (CNTs). Diamond as well as graphite are both
allotropes of carbon. Diamond is a hard material, whereas graphite is relatively soft.
Diamonds, along with graphite, include carbon atoms arranged in hexagonal or cubic
2
lattices. The carbon atoms in both materials exhibit sp
or sp3hybridization. Carbon
nano-onions (CNOs) have garnered significant attention from both academic and
commercial sectors due to their various applications in biology [79]. Using carbon
nanostructures in medical applications is highly desirable depending on exceptional
characteristics such as substantial surface area, electrical conductivity, mechanical
robustness, and various other advantages [80]. This review included a variety of
carbon-based nanomaterials (CNMs), each with their strengths and cons (Table 1).
•
The ability to stack supramolecular is the key to their great drug absorption.
•
CNMs have distinct optical properties and combine well with luminous
substances, making them potential theragnostic.
•
Furthermore, it is worth noting that carbon nanomaterials (CNMs) exhibit a
remarkable ability to convert heat, particularly in the near-infrared spectrum.
This characteristic makes CNMs highly suitable for applications in photothermal
therapy.
•
Tunable surface chemistry helps to regulate drug release.
In the context of biological applications, using covalent and non-covalent functionalization techniques on carbon-based nanomaterials (CNMs) has been shown
to enhance the colloidal stability of these materials in aqueous solutions. Oxidation, dehydrogenation, plasma, and ozonolysis are covalent functionalization techniques. CNMs can cross biological membranes and deliver drugs. Functionalization with a specific ligand minimizes loaded drug cytotoxicity to healthy cells and
improves therapy. Drug-loaded carbon nanomaterials (CNMs) have the potential to
be coupled with various small targeting molecules. Some solid tumor cells exhibit
folate receptors on their surface, which can be targeted using folic acid. Tumorassociated antigens can also be identified using antibodies, and ligands having an
affinity towards a receptor overemphasized on a particular tumor type can be used.
In addition, drug-loaded CNMs can benefit from adding magnetic nanoparticles,
increasing their specificity. Carbon nanomaterials (CNMs) have many potential uses
in oncology, s uch as in the creation of anticancer medications, the discovery of fluorescent markers for tumor identification, the administration of cancer phototherapy,
and the performance of theragnostic.
Carbon Nanomaterial-Incorporated Supramolecular Drug Delivery 149
Tabl e 1 CNMs’ benefits and drawbacks. Adapted and reproduced with permission from MDPI
[80]
Serial
number
1 Graphene quantum
2 Nanodiamonds TheCNMshaveseveraldesirable
3 Fullerenes Superconductivity,
4 Carbon nanotubes Very high aspect ratio, mechanical
5 Carbon
Carbon-based
nanomaterials
dots/graphene
oxide/graphene
nano-onions
Effects Confines in biomedical
Superior electrical, thermal, and
optical properties. Graphene’s
atomic sheet structure in just two
dimensions gives it superior
electrical characteristics versus
CNTs
properties, including fluorescence
and photoluminescence, a smaller
size than competing CNMs,
resistance to corrosion and
durability, as well as high
electrical and chemical inertness
photoelectrochemistry, and surface
modification
strength, chemical stability, and
conductivity. Offers high surface
area, biocompatibility, and the
ability to tune its physical
properties
Exceptional electrical and
structural properties, including
reversible electron uptake, broad
absorption bands, and a high
surface-to-volume ratio
applications
Colloidal instability,
repeatability, poor
chemical stability, limited
synthetic control in
biological environments,
and oxidative vulnerability
Covalent manufacturing,
toxic organic solvent
removal, sudden drug
release, and inclination to
agglomerate make it
difficult
Low aqueous
solubility, cell membrane
accumulation, light and
oxygen
degradation, quenching
susceptibility
Non-homogenous size
(length and diameter) and
metallic impurities.
Powdery Pristine CNTs
can enter the respiratory
tract
Aggregation,
hydrophobicity,
insufficient surface
chemical reactivity,
oxidation susceptibility,
and poor biocompatibility
4.2 Examples of Carbon Nanomaterial-Incorporated
Supramolecular Drug Delivery Systems
4.2.1 Carbon Nanotubes (CNTs) for Drug Delivery
Scientist Ijima used the carbon arc discharge method to create “multi-walled carbon
nanotubes,” needle-like graphene sheets, in the early 1990s [25]. Compared to other
materials used for sensing, diagnostics, and medication delivery, single- and multiwalled carbon nanotubes (CNTs) are superior because of their exceptional structural,
electrical, and mechanical capabilities. The confinement of quantum particles along
the tube’s axis conserves electrons. CNTs also exhibit van Hove singularities and
150 N. T. Tuli et al.
a uniform Density of States (DoS). Diameter and chirality determine the DoS. The
valence-conduction band gap decreases with the diameter of CNTs. Both bands
create metallic nanotubes. Pristine CNTs are hydrophobic due to their size, structure, and bundling effect, restricting their biological absorption. Functionalization
reduces nanotube surface bundling, enhancing biocompatibility and cellular internalization. Functionalized nanotubes were biocompatible in vivo and in vitro. The
level of functionalization is determined by factors such as sidewall behavior, reactivity (curvature), the number of attachable functional groups, and the steric barrier
between the functional categories and the nanotube sidewall. Various methods can be
employed to affix drugs onto carbon nanotube (CNT) sidewalls, including both covalent and noncovalent bonding approaches. Table 2 lists drug delivery breakthroughs
using carbon nanotubes (CNTs).
4.2.2 Graphene Oxide (GO) for Drug Delivery
Simple physisorption by stacking can absorb DOX, antibodies, and docetaxel onto
graphene. Graphene’s ability to stack and interact electrostatically or hydrophobically allows for the safe transfer of pharmaceuticals that aren’t easily soluble.
Table 3 shows GO-based medicine delivery uses. Using graphene oxide-zoledronic
acid (ZOL-GO), Mahor et al. [80] studied cells in vitro. The morphology of MCF-7
breast cancer cells and the mineralization of BM-MSCs were analyzed. Nanostructured ZOL-GO mineralized BM-MSC cells in clusters. Highly effective quercetinloaded single-layer graphene oxide (GO) sheets, grafted with hyperbranched polymer
(HPG) on their surface, were successfully synthesized through the polymerization
of glycidol. The Hummers process was enhanced. Drug-loading and encapsulating
HPG stabilized GO sheets in biological fluids. The administration of quercetin was
regulated and maintained by HPG-GO, while it was proposed that an acidic pH could
enhance the release of the medicine.
4.2.3 Carbon Nano-Onions (CNOs) for Therapeutics Delivery
CNOs are extensively exploited in drug administration, tissue engineering,
bioimaging, sensing, cancer treatment, and CNS diseases (Table 4). Using
supramolecular functionality in the context of stimuli-responsive biocompatible
polymers enables the controlled delivery of customized pharmaceutical agents
through carbon nanotubes (CNOs) [94]. Narsimha et al. developed a nanocomposite
fiber consisting of bovine serum albumin (BSA) embedded with Forcespinning® (FS)
4-hydroxyphenyl methacrylate-carbon nano-onions (PHPMA-CNOs = f-CNOs).
This fiber was designed to administer doxorubicin (DOX) in a stimuli-responsive
manner [17].
Tabl e 2 Recent development in transport using carbon nanotubes. Adapted and reproduced with permission from MDPI [80]
Serial
Disease CNT functionalization Drug/Vaccines/Genes Results References
Number
1 Cancer MWCNTs/Gemcitabine (Ge)/
Lentinan-Le
Gemcitabine–Lentinan Increased chemotherapeutic and synergistic
photothermal action against tumors were seen using
MWCNTs-Ge-Le
2 Bladder cancer Magnetic MWCNTs-Epi Epirubicin (Epi) The application of an external magnetic field
significantly enhanced the anticancer activity of
multi-walled carbon nanotubes (MWCNTs) in both
in vitro and in vivo settings, surpassing the
effectiveness of free epirubicin
3 Cell proliferation Hydrogels of PEG-CNTs Tissue engineering The cytocompatibility, proliferation of L29
fibroblasts and viability were all improved by
exposure to pure CNTs and PEG-CNT hydrogels
4 Ischemic brain
tissue
PEGylated vertically aligned
MWCNTs
Dexamethasone The MWCNTs exhibited minimal cytotoxicity when
tested on the PC-12 cell line
5 Antileishmanial Ci-SWCNTs, Ci-MWCNTs Cisplatin (Ci) In vitro, the growth of Leishmania major was
effectively suppressed by Ci-MWCNTs at low
concentrations
6 Cancer therapy N-isopropyl acrylamide
carbon nanotubes loaded with
DOX
Doxorubicin (DOX) The incorporation of a five-mer N-isopropyl
acrylamide molecule resulted in enhanced DOX
loading through the formation of hydrogen bonds
with the drug
Carbon Nanomaterial-Incorporated Supramolecular Drug Delivery 151
[80]
[81]
[82]
[83]
[84]
[85]
(continued)
Tabl e 2 (continued)
Serial
Number
7 Antibacterial
8 Peptide delivery The casing of SWNTs with
Disease CNT functionalization Drug/Vaccines/Genes Results References
activity
Glucose-modified calcium
alginate single-walled carbon
nanotubes (CA/SWCNT-Gl)
polycationic and amphiphilic
peptides
[H-(-Lys-Trp-Lys-Gly-)7-OH]
Curcumin The Gl nanocomposite exhibited superior efficacy
compared to Escherichia coli and Bacillus cereus
compared to CA/SWCNT
GS-protein PEGylation increases absorption by seven times [87]
[86]
152 N. T. Tuli et al.
Carbon Nanomaterial-Incorporated Supramolecular Drug Delivery 153
Tabl e 3 Drug delivery using graphene derivatives. Adapted and reproduced with permission from
MDPI [80]
Serial
number
1 GO Zoledronic acid Bone marrow-derived
2 GO Doxorubicin In vitro: drug statement [89]
3 Pristine graphene andGODoxorubicin In vitro: pH imitation [90]
Graphene derivative Therapeutic agents Application and outcomes References
[88]
mesenchymal stem cells
(BM-MSC) and Michigan
Cancer Foundation-7
(MCF-7) breast cancer
cells
4 PEG-functionalizedGOCephalexin CEF release in vitro was
5 GO nanosheets
doped into ZnO NPs
6 GO Chloramphenicol,
Doxorubicin The drug loading accuracy
ampicillin,
tetracycline
burst, constant, and 80%
cumulative.
GO-PEG-CEF’s
antibacterial efficacy
against Gram-positive and
Gram-negative bacteria
was dose- and
time-dependent
was 89% for GO-doped
ZnO NPs and 82% for
ZnO. The system improved
drug dissolution
GO synergistically kills P.
aeruginosa, E. faecalis, and
E. coli, and harms human
epidermal keratinocytes
(HaCaT)
[91]
[92]
[93]
5 Drug Delivery Systems Based on Carbon Nanomaterials
Associated with Supramolecules
In recent years, there has been a notable increase in the interest in drug delivery
methods that utilize carbon nanomaterials in conjunction with supramolecules such
as cyclodextrin, calixarenes, cucurbituril, pillarenes, and crown ether. These systems
exhibit potential for optimizing the targeted administration of pharmaceuticals,
improving their bioavailability, and mitigating potential adverse effects. Here’s a
concise summary of the various applications of supramolecular structures in drug
delivery systems incorporating carbon nanomaterials.
Tabl e 4 CNO biomedical advancements. Adapted and reproduced with permission from MDPI [80]
Serial number Delivery system Application Results Reference
1 f-CNO-reinforced zein hydrogels Anticancer drug delivery Zein hydrogels were fortified by f-CNOs.
[95]
The mode of distribution proved safe for
osteoblasts to process. The pH-dependent
release of the drug lasted for 15 days
2 Ox-CNO-loaded chitosan polyvinyl alcohol
(CS/PVA/oc-CNO) nanocomposite film
Tissue engineering application The scaffold composed of CS/PVA/ox-CNO
exhibited enhanced stability. The Wistar rats
[96]
that were subjected to implantation of the
nanocomposite film did not exhibit any
adverse reactions or the formation of pus.
The CS/PVA/oc-CNO scaffold demonstrated
the capability for tissue regeneration
3 Polycaprolactone/f-CNO nanocomposite
fiber
Anticancer drug delivery PCL or f-CNO nanocomposite fiber released
DOX pH-dependently. PCL nanofibers were
[97]
stronger, hydrophobic, and biocompatible
with F-CNOs
(continued)
154 N. T. Tuli et al.