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186 Carbon-Based Nanocarriers for Drug Delivery
unalterablyeliminated by the kidney [4]. Water-soluble fullerenes were discovered to
have very low acute toxicity [22]. Fullerenes may be used in biology and medicinal
chemistry due to all these intriguing features, which indicate a promising future for
them as pharmaceuticals. Nevertheless, there is a considerable obstacle to this potential, namely fullerenes’ inherent anisotropy toward the water. Several approaches are
being explored to get over this restriction. Among them involve the development of
fullerene derivatives with altered solubility proles, the embedding of C60 in cyclodextrins or calixarenes, or formulations in aqueous suspension. Fullerene derivatives
have been produced in large quantities.
Fullerenes have been the subject of several inventions, and the fullerene patent
repository is expanding quickly. As fullerenes and their derivatives showed early
signs of potential activity in numerousmedicinal elds, such as nucleic acid delivery,
chemotherapeutics, and neurodegenerative diseases,they are currently the subject of
extensive research.
The primary function of fullerenes is to serve as a photosensitizer for the photoproduction of singlet oxygen (1O2) ROS; as a result, they are used in photodynamictreatment (PDT)and blood sterilization [23–25]. Regrettably, the dispersibility
of fullerene is a substantial hurdle to its use in nanomedicine. The main problem
is their inability to dissolve in many solvents, notably water, where singlet oxygen
has a lengthy lifetime. Avariety of approaches have been developed to functionalize fullerenes with hydrophilic groups in order to improve their solubility in water
[26,27]. The ability of fullereneto scavenge free radicals like reactive oxygen species
(ROS) and reactive nitrogen species (RNS) and serve as an antioxidant has boosted
its adoption in biological applications. Cells can be shielded against nitric oxideinduced apoptosis with the use of derivatives of glutathione C60 [28].
When pre-incubated with C60, the IgE-dependent mediators generated by human
mast cells (hMCs) and peripheral blood basophils were signicantly inhibited, supporting the role of fullerenes as a strong allergen inhibitor [29]. Fullerenes may have
the capacity to serve as photosensitizers. They may absorb photons in the visible and
UV range depending on the polarity of the medium, leading to the production of
photo-excited fullerene molecules in the triplet state and, in certain situations, singlet
oxygen or ROS. Additionally, fullerenes might be used with light- harvesting antennas to increase the quantum yield (QY) of ROS formation. So, the use of fullerenes
in PDT can be utilized to treat cancer and get rid of germs. The cage-like nanoscale
structure of fullerenes enables the development of molecular or particulate structures, including one or even more organic chemicals covalently bonded to the fullerene cage surface in a geometrically controlled manner. For the purpose of inhibiting
cellular and enzymatic activity, targeted drug transport through biological membranes and receptor ligands are acceptable. The liposome encapsulation technique is
a different way of developing fullerenes to be utilized in pharmaceutical applications
with better dispersion, absorption, and delivery efciency [30].
Although signicant scientic advances have been achieved in the realm of fullerene treatments, the failure of clinical studies results from worries regarding the longterm safety and toxicity of fullerene. Yet since fullerene-based cosmetics have been
used for a long time in human skin care and have passed clinical testing, it is safe to
apply them externally at most [31,32]. The sturdy cage-like structure of fullerenes
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allows for enough room for the encapsulation of atoms, drug molecules, and particles. For instance, highly reliable water-soluble gadolinium metallofullerenes
(gadofullerenes) are incredibly fascinating MRI contrast agents. Fullerenes may
self-assemble into fullerosomes, which are multivalent drug delivery systems (DDSs)
with the potential for diverse targeting properties [33].
7.4 METHODS FOR THE SYNTHESIS OF FULLERENE
For decades, carbon clusters have piqued the interest of researchers in numerous
elds. Researchers from a variety of backgrounds, including chemists and engineers,
are always looking for new ways to use their ndings in areas such as catalysis and
combustion. Little carbon clusters have been detected in carbon stars and comet tails,
and astrophysicists are trying to gure out what role they play. Moreover, the discovery of C60 buckminsterfullerene may be traced back to the earliest investigations into
carbon cluster production. Keep in mind that the accidental synthesis of fullerenes
may be traced back to basic science. Carbon-cage clusters, their genesis, fundamental science, and application development continue to pique researchers’ interests
today. Graphite and diamond are two allotropes of carbon that have been known for
ages. The fullerene timeline, in contrast, did not progress until the 1980s, when many
signicant investigations were conducted. Fullerenes were rst made experimentally
and found during this decade [34].
The investigation conducted by Krätschmer and Huffman was pioneering for the
synthesis of fullerenes in 1990 and marked a turning point in the production of cageless molecules [35]. Some contemporary laboratories continue to rely on the electric arc approach, which vastly improves the accessibility of C60 and C70 fullerene
samples. Due to the abundance of pure C60 available to scientists throughout the
1990s, the number of fullerene-related investigations surged considerably. Numerous
long-awaited fullerene research is now feasible due to a shift in emphasis from laser
vaporization to electric arc. It took another ve years (1990) for electric arc synthesis, invented by Krätschmer and Huffman, to replace the microgram quantities
previously produced by the laser vaporization technique (1985) [35,36]. This electric
arc method ultimately becomes the most important method for mass-producing kilogram quantities of fullerene soot. The arc reactor generated gram-scale quantities
of puried and widely dispersed C60 in the 1990s and beyond. Early in the 1990s,
a fundamental question is posed. Both lasers and electric arcs have been utilized in
the production of fullerenes. Intuitively, one may consider various methods for evaporating a carbon source in a low-pressure environment containing helium or argon.
Numerous attempts to produce fullerenes between 1990 and 2022 are reported and
will be briey discussed next. Solar energy, a radio-frequency furnace, chemical
vapor deposition (CVD), and combustion are some of the more unusual techniques
that may be utilized to make them.
7.4.1 gas-phase meThoD
In 1991, researchers at the Massachusetts Institute of Technology evaluated the possibility of producing fullerene in soot-laden ames. In their ground-breaking study,
188 Carbon-Based Nanocarriers for Drug Delivery
Howard etal. show the synthesis of C60 and C70 fullerenes utilizing a ame technique [37]. The authors describe how pressure (20 torrs), temperature (1800 K),
carbon-to-oxygen ratio (0.995), and ame residence time impact the combustion and
condensation of hydrocarbons. When these factors are tuned, one kilogram of carbon
fuel yields three kilograms of fullerenes [37]. This unique combustion technique
using ames indicates promise as early as 1991, just one year after the K-H electric
arc synthesis was introduced [35,38]. The operator may change the ratio of C70 to C60
fullerenes, which is one of the ame method’s less-discussed attributes. The ratio
C70/C60 may be altered from 0.26 to 5.70 by modifying the experimental conditions.
Controlling the formation of fullerenes is a signicant nding about their origin.
The authors also observe and examine how the development of fullerenes differs
from that of soot [37]. For example, the sootiest ames do not always create the
most fullerene. In fact, fullerene yield increases with either 1. decreased pressure or
2. increased temperature [37]. The MIT group in 1996 released another signicant
study on the combustion technique employing benzene, oxygen, and argon ames
[39]. This later attempt aims to examine higher fullerenes, which represents a signicant shift from the rst. The HPLC techniques used to generate, extract, and separate
them are of tremendous interest. Beyond C60 and C70, all fullerenes are sought. C76,
C78, C84, C90, and C96 are merely a few of the larger cage constructions that are being
considered for production and isolation [39]. They emphasize the importance of solvent selection while attempting to extract this lesser-known, higher fullerenes. To
remove soot efciently, they designed a method of advanced extraction using several
solvents [39].
In 1991, Howard etal. rst introduced the notion of employing a bigger ame
for industrial-scale fullerene manufacturing. Due to industry investment, their commercial production became a reality 13years later, conrming that their prediction
was accurate [37]. The combustion synthesis was developed by TDA Research and
Frontier Carbon Corporation (formed in Japan as a joint venture by Mitsubishi in
December2001) to produce fullerenes on an unprecedented scale of tons per year
[40]. The transition of fullerene production from university laboratories to the industrial setting has reduced the ten-year reliance on solitary academic groups for sample
collaborations. Instead, they would be made and sold inexpensively by a business.
By doing so, the sample availability issue that has plagued the business for decades
would be resolved (1985–2004). Its commercialization constitutes a major scientic
advancement in the realms of ame-based technology, low-cost hydrocarbons, and
continuous-ame synthesis [40]. When experiments are improved, soot collected by
the ame method has the potential to contain as much as 20% fullerene. In addition
to the cost of raw materials, the authors emphasize the importance of other industrial
processes [40].
7.4.2 arc Discharge meThoD
From 1985 to 1990, evidence of the presence of fullerenes increased. Several laboratories undertook independent, repeatable synthesis and mass spectrometry-based
identication of their presence [41]. During this period, scientists intended to increase
fullerene production from micrograms to milligrams. Due to the exceedingly low
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yield of soot and fullerenes that could be removed, the laser extraction technique of the
1980s was problematic. Despite increased interest in soot and fullerenes, researchers
needed a more efcient way of generating these substances. Without huge amounts of
pure C60 and C70 samples, a paradigm shift in fullerene manufacturing was required
for several planned experiments. From this perspective, it is simple to understand
why Huffman’s technique of creating fullerenes made such a stir and had such a deep
impact [35,38,41]. Their electric arc synthesis has made it possible for the rst time
to produce soot and fullerenes in the gram range. They may apply their arc approach
with any chamber design without incurring excessive costs. With this electric arc
process, it is also feasible to create nanotubes, endohedral metallofullerenes, and
empty-cage fullerenes. In 1990, Krätschmer and Huffman’s research team published
two essential studies [35,38]. They discovered that graphite rods could be vaporized
by resistive heating in the presence of a quenching gas. The collected carbon smoke
particles are then studied further. The authors provided experimental evidence for
an all-carbon, icosahedral C60 molecule by comparing the infrared and ultraviolet
absorption spectra of C-12 and C-13 tagged samples resulting from their arc synthesis [38]. The observed number of bands was consistent with theory, conrming
the symmetric, soccer-ball-shaped C60 structure. Remember that the foreshadowing
would come in the last sentence of their report. They anticipated that their K-H arc
approach would enable the extraction of huge quantities of fullerenes from soot [38].
Time validated their concluding assertion. In the year 2020, 30years and a global
pandemic later, their electric arc technology is still extensively used to manufacture
carbon nanomaterials. In September 1990, Nature published “Solid C60: a unique
form of carbon” by Krätschmer and Huffman as their second article [35]. Macroscopic quantities of isolated C60 were produced, separated, and characterized, illuminating the methods involved. This research described the unique electric arc method
experimentally. Resultantly heated carbon rods were vaporized at 100 torrs of He
buffer gas. Gram quantities of fullerenes were extracted from soot using an aromatic
solvent (benzene). Adding solvents like carbon disulde or carbon tetrachloride may
also dissolve and extract fullerenes from the soot matrix. Krätschmer and Huffman
proposed sublimation as an alternative to solvent extraction for extracting fullerenes
from soot and producing thin layers of C
-coated surfaces [35]. In actuality, IR and
60
UV-Vis spectroscopy was employed to characterize these coatings. This is largely
recognized as the rst source chronicling the evolution of the electric arc approach
for producing fullerenes. This research comprises some of the initial experimental
characterizations of C60. The arc process facilitated thesynthesis of substantial quantities of pure C60, which made this achievement feasible [35]. In addition, Krätschmer
and Huffman were able to isolate 100 mg of C60 in just one day, an achievement that
goes back 30years to this inuential article. In the concluding portion of this second
research, the authors predicted the effects of their electric arc discovery, as they did
in their investigation [35,38]. Krätschmer and Huffman’s electric arc approach for
synthesizing fullerene is well-known among researchers working with carbon nanomaterials today. In current times, the pioneering characterization investigations that
empirically veried C
’s Ih structure are rarely accorded the respect they deserve
60
[35]. In December1990, Hauer etal. successfully extracted grams of C60 using an
electric arc reactor [42]. Evident are the best parameters for its synthesis. The reactor
190 Carbon-Based Nanocarriers for Drug Delivery
was pressurized to 100 torrs, the bleed rate was 1 sccm, the current was between 100
and 200 amps, and the RMS voltage was between 10 and 20volts [42]. This system
generated 10 g/h of soot. While doing the extraction, the authors selected a process
unique from that of Krätschmer and Huffman. Instead, Smalley’s team produced
around 10% extractable fullerenes from soot by boiling toluene for three hours in a
Soxhlet extraction [43]. In terms of the ratio of fullerene to soot, their performance is
comparable to that of a number of commercially marketed electric arc reactors. The
rst experimental reactions with C60 were also documented. In 1990, electrochemical
approaches were added to the ever-expanding palette of conclusive methods for characterizing C60. The Birch reduction was employed to produce C60H36, and the DDQ
reagent was then used to remove the hydrogen, leaving pure C60 [42]. In doing so,
they created a reversible reaction with C60. The chemistry of functionalizing the surfaces of fullerene cages has begun. Hauer foresaw the importance of their reactivity
discoveries, predicting a chemically derivatized rich outer surface of fullerenes, and
theorized that metal atoms could be utilized inside the cavity to ne-tune the fullerene’s electrical and optical properties [42]. Exohedral functionalization and endohedral encapsulation, two prospective study subjects, have witnessed the publication of
tens of thousands [41]. In another study, the authors improved their reactor parameters (current, rod diameter, graphite supply, helium pressure, and soot extraction
technique) to increase the extractable yield of soluble fullerene to 14% [44,45].
7.4.3 microwaVe-BaseD process
In addition to the well-known methods outlined before, there exist technologies that
synthesize fullerene using microwaves. In 1995, Ikeda etal. reported successfully
synthesizing fullerene using naphthalene and microwave-induced N2 plasma in a
cylindrical coaxial cavity at atmospheric pressure. In nitrogen plasma generated by
microwaves, molecular species like benzene and naphthalene may be excited and
ionized, and the plasma state can be easily regulated [46].
Recent research has investigated the prospect of utilizing microwaves to transform
graphite powder into fullerenes, therefore creating a new route for fullerene production. As it evenly warms the precursors, the microwave technique offers advantages
over more conventional heating methods. The amount of graphite powder utilized
and the microwave power led to a higher yield of produced fullerene, but time and
temperature had no inuence on fullerene synthesis [47].
7.5 FUNCTIONALIZATION OF FULLERENE
Fullerene’s distinct physical and chemical properties make it a promising candidate
for use in biological and material chemistry applications, although the molecule is
often functionalized before being put to such uses [48]. Fullerene C60 has many interesting features, but its insolubility in water and limited solubility in many organic
solvents prevent it from being used in biological applications [49]. Functionalizing
fullerene relies heavily on its double-bond structure. They may participate in additional reactions, allowing for modifying the carbon cage’s outer sphere and synthesizing derivatives with a wide range of functional groups [50]. As pure fullerene
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lacks a hydrogen atom, it is unable to participate in substitution processes; nonetheless, fullerenes are oxidizing agents and may generate active oxygen forms when
exposed to UV-visible light [48].
Fullerenes can be altered in two ways: 1. by covering up part of the fullerene
surface with a solubilizing agent and 2. by chemically altering the fullerene by
covalent functionalization [48]. The rst group can benet from inserting fullerene
into articial lipid membranes, inducing co-solvation with polyvinylpyrrolidone
in organic solvents and attaching polymer chains to fullerene [48,51]. The hydrophilicity of fullerene and the range of its biological and pharmacological uses have
been improved by a variety of functionalization techniques. The transformation of
fullerene’s carbon atoms from sp2 to sp3 hybridization is the driving force behind
the reaction [52]. Molecules can be covalently conjugated to C60 by free-radical processes, cyclopropanation, or cycloaddition reactions such as [1 + 2], [2 + 2], [3 + 2],
and [4 + 2] [52]. As a result of its electron-decient state, fullerene reacts in a wide
range of cycloaddition reactions, including [1 + 2], [4 + 2] (Diels-Alder reactions),
[3 + 2], and [2 + 2]. Several cycloaddition procedures have been used to create a wide
variety of fullerene derivatives [53]. The latter strategy, chemical modication, is a
cutting-edge and efcient approach that yielded several fullerene derivatives with
attached amine (-NH2), hydroxyl (-OH), and/or carboxyl (-COOH) groups, including
examples of some of the so-obtained derivatives.
Brettreich etal. used a dendrimeric approach to attaching carboxylic groups to
fullerene, which increased the molecule’s solubility in water and achieved excellent results among the many fullerene functionalizing approaches [54]. To improve
fullerene solubility in aqueous and polar environments, Filippone etal. synthesized
a (permethylated-cyclodextrin)-fullerene conjugate by covalently linking C60 and
cyclodextrins. Fullerenols, which have a C60(OH)n formula and include a hydroxyl
group, are very soluble in water and have been used to neutralize oxygen-free
radicals and protect neural tissue [55]. In addition, amyotrophic lateral sclerosis
(ALS) patients have beneted from carboxy fullerenes in the therapy of neurodegeneration [56].
7.6 APPLICATIONS OF FULLERENE
Fullerenes are a family of carbon-based nanomaterials with distinctive structural
and electrical features that make them desirable for a broad variety of applications,
including medication administration. Its usage as a medication delivery system is
one of the most promising uses of fullerenes. Fullerenes may be functionalized with
hydroxyl, carboxylic acid, and amine groups, enabling their usage as nanocarriers
for the delivery of drugs. Fullerenes’ huge surface area gives adequate space for drug
loading, while their unique physical and chemical characteristics allow for effective
drug transport to target cells or tissues. Using fullerenes as medication delivery systems offer several benets:
• Biocompatibility: it has been demonstrated that fullerenes are biocompatible and do not generate considerable toxicity, making them excellent for use
in biomedical applications.
192 Carbon-Based Nanocarriers for Drug Delivery
• Fullerenes can prevent the degradation of medicines, enhancing their stability and extending their half-life in the body.
• The functionalization of fullerenes with targeting moieties, such as antibodies or peptides, enables the selective delivery of medications to specic cells
or organs.
• Fullerenes have unique optical and magnetic characteristics that can be utilized for biological imaging techniques like uorescence and magnetic resonance imaging.
• Fullerenes may be functionalized with a variety of functional groups, enabling its usage in diverse applications, including medication administration
and imaging.
Despite these benets, the use of fullerenes as a drug delivery method is not without
its drawbacks. For instance, fullerenes are rapidly eliminated from the body, which
might reduce their effectiveness. Researchers have devised techniques to improve
the stability and bioavailability of fullerenes, including encapsulation in liposomes
and polymer nanoparticles. Fullerenes have demonstrated considerable potential as
drug delivery systems owing to their biocompatibility, drug stability, targeted drug
delivery, imaging capabilities, and multifunctionality, among other features. This
section focuses on the use of fullerenes as a carrier for nucleic acid-based medicines,
along with its prowess in cancer and neurodegenerative therapeutics. However, further study is required to enhance their design and increase their clinical effectiveness
and safety.
7.6.1 nUcleic aciD DeliVery
Fullerene and its functionalized derivatives have been researched for possible
medicinal applications because of their distinctive characteristics. Theoretically,
compounds from this class may serve as carefully regulated drug delivery systems.
Fullerene and its functionalized derivatives are a relatively recent medicinal technique for nucleic acid delivery. The method entails targeted distribution in cells
devoid of nucleic acids. The vast majority of approaches for targeting the transfer of
DNA, RNA, siRNA, LNA, and plasmid DNA to specic cellular locations rely on
viral delivery [57]. Small chemicals have been transported by nanoparticles, such as
fullerenes, in a number of investigations because of their low cost, high efciency, and
absence of allergic reactions [58]. In a pH-balanced solution, a cationic tetra-amino
fullerene and siRNA form nanoscale complexes. When these complexes agglutinate
with plasma proteins in circulation, micrometer-sized particles are generated. After
inhibiting the expression of certain cancer genes, the agglutinate is swiftly eliminated from the lung [59]. This is because it quickly clogs the capillaries in the lungs.
Further research revealed that a certain amphiphilic skeleton of C60-Dex-NH2 may
form micelle-like aggregation structures in water, therefore shielding siRNA against
oxidative destruction. When exposed to visible light, C
ROS generation leading to lysosome membrane breakdown, enabling lysosomal
escape, and enhancing the in-vitro and in-vivo efciency of siRNA gene silencing.
Both MDA-MB-231-EGFP cells and 4T1-GFP-Luc2 tumor-bearing mice showed a
-Dex-NH2 caused regulated
60
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maximum gene silencing efciency of 53%. According to the published research,
conjugated nucleic acids supplied via fullerene-based systems signicantly enhance
the specicity of their effects on their intended targets. At the same time, healthy
cells are considerably more resistant to adverse effects [60].
7.6.2 chemoTherapy
Causes of cancer include chemical or poisonous chemicals, ionizing radiation,
viruses, and human genetics [60]. Cancer is the uncontrolled proliferation of aberrant cells in the body. Cancer treatments have historically used a wide variety of
medications. The biggest issue with cancer treatment is the severe adverse effects
of the medications, which need careful dosing [61]. Drug resistance is another problem in cancer treatment, forcing doctors to utilize combinations of medications with
additive side effects.
Fullerene, a nanoparticle with promising structural properties for use in medication administration, is one example. Many of the negative effects of chemotherapy
may be alleviated, thanks to fullerene, because it can transport a large number of
drugs and deliver them precisely 22, 23. For instance, doxorubicin has the potential
for conjugation with fullerene because of the cardiomyopathy-related adverse effects
of this drug [62]. This conjugation was tested at various pH levels, and ndings
showed that drug release was maximized at a pH of 5.25. Based on the ndings, such
conjugation for selective medication delivery with minimal unwanted consequences
can be employed. As fullerene is hydrophobic and doxorubicin is water-soluble, this
strategy required the insertion of ethylene glycol spacers to improve the water solubility of the doxorubicin-methano-C60 conjugate [48]. Another study covered paclitaxel’s hydrophilic surface by using Buckysomes, which are spherical nanostructures
composed of amphiphilic fullerenes with hydrophobic areas. According to the results
of this research, the suggested complex has the potential to signicantly improve
medication absorption [63].
By attaching a hydrophilic shell to the outer surface of the conjugation of doxorubicin and fullerene, researchers were able to create a new, unique drug delivery
system based on an “on-off” drug delivery method. In its inactive (“off”) form, this
drug delivery system is relatively stable in physiological solutions, down to a pH of
5.5; in its active (“on”) state, however, fullerene’s ROS production leads to two distinct treatment modalities. The rst is the production of oxygen radicals that kill cells
(programmed cell death; PDT), and the second is the explosive release of doxorubicin (chemotherapy) by destroying the ROS-sensitive linkers [60]. Several nanomaterials have been investigated so far in the development of revolutionary techniques for
cancer treatment; nevertheless, fullerene and fullerene-based systems are among the
most promising alternatives due to their distinctive structures and features.
7.6.3 neUroDegeneraTiVe Diseases
Drug delivery to the CNS is complicated by the presence of the blood-brain barrier,
a physical barrier formed of tight endothelial junctions that restrict paracellular permeability [60]. Nanomaterials with great potential for transporting medications into
194 Carbon-Based Nanocarriers for Drug Delivery
the brain include fullerene and its water-soluble derivatives. The research examined
the effectiveness of a hexamethonium delivery method with and without a fullerene complex. According to the study, the sophisticated medication delivery method
increased efcacy by a factor of 40. Water-soluble derivatives of C60 fullerene were
synthesized in another work, this time using four different types of connections
between the fullerene cage and the solubilizing added atoms [64]. The proliferation
of neural stem cells (NSCs) was induced in-vitro by fullerene derivatives 1–6 (com-
pounds 1–3 contain C–C bonds; compounds 4–5 contain C–S bonds; and compound
6 contains C–P bonds), and the function of the injured central nervous system in
zebrash was restored.
Interestingly, compound 3, which included phenyl butyric acid residues, dramatically increased NSC proliferation and brain repair through a shift in cellular
metabolism that resulted in a decrease in reactive oxygen species (ROS) activity
and an increase in adenosine triphosphate (ATP) activity. Compounds 7–9, which
are fullerene derivatives, have been shown to limit the growth of glioblastoma cells
in zebrash. Compound 7, which included phenylalanine tails, dramatically slowed
glioblastoma development and served as an anticancer agent. Metabolic alterations
in the cells were linked to the aftereffects of increased ROS activity and decreased
ATP activity [64]. The neurodegeneration associated with amyotrophic lateral sclerosis (ALS) has also been treated by means of carboxy fullerenes [65]. The brain’s
intricate anatomy inherently prevents any substance from crossing the blood-brain
barrier. Despite this restriction, therapeutics can be delivered through the twisted
structures of fullerene-based delivery systems.
Maintaining a healthy level of oxidation and antioxidant activity inside the body
is crucial to the integrity of our biological system. Toxicities and illnesses induced by
excess free radicals, such as cancer and atherosclerosis, necessitate the administration of exogenous antioxidants due to our insufcient endogenous antioxidant defense
system and the huge free-radical synthesis by normal cellular metabolism and aberrant responses [60]. These nanoparticles are able to react with free radicals, including superoxide, hydroxyl radicals, and hydrogen peroxide, because of the presence of
many double bonds in the fullerene cage [48]. Two types of fullerenes, C60 and C82,
were employed as antioxidants in a recent study. These fullerenes were conjugated
with copper, silver, and gold. Results showed that fullerenes’ antiradical ability was
enhanced in the presence of the metals [66]. Fullerene’s antioxidant properties have
been used in anti-aging skincare and beauty products, according to previous studies
[67]. Asuspension of fullerene with an average size of 450 nm was created and injected
into the hippocampi of Wistar rats, demonstrating its capacity to pass the blood-brain
barrier. Although the results showed a decline in spatial memory and BDNF protein
levels, the results also showed a decline in reactive oxygen species [68]. Fullerenols
were examined for their antioxidant capabilities in oxidizing solutions, including luminescent bacteria and their enzymes. Catalytic activity was linked to the enhancement
of biological processes, and the hormesis phenomenon was shown to be responsible for
the effect on bacterial cells [69]. Oxidative stress is a leading cause of modern society’s
most pressing issues. The oxidative stress system may be brought into equilibrium
using fullerene-based systems. Further research is needed to properly comprehend the
signicance of fullerene-based delivery methods in regulating oxidative stress.
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Neurodegenerative illnesses like Alzheimer’s and Parkinson’s have been linked to
the overproduction of oxygen species and the hyperactivation of N-methyl-d-aspartic
acid or N-methyl-d-aspartate (NMDA) and glutamic receptors [60]. The major reasons fullerene derivatives were used in neurological illnesses were their radical scavenging capacity, their ability to activate reactive oxygen species, and their ability to
bind with peptides [48]. Their peptide-interacting abilities have also been used in the
ght against Alzheimer’s disease. The major amyloid-forming component of yeast
prion protein Sup35, the hydrophilic GNNQQNY peptide, was examined for its sensitivity to the hydrophobic fullerene C60 in an experiment [70]. In addition to blocking
the inter-peptide interactions necessary for oligomerization and β-sheet formation,
the results showed that fullerenes totally prohibit bril-like bilayer β-sheets, generated by GNNQQNY peptides [70]. Oxygen species inhibited A-beta and reduced
concomitant cytotoxicity when UCNP@C60-pep was exposed to near-infrared light,
resulting in ROS species. Antioxidant activity in fullerene and fullerenols has been
quite impressive. It has been observed that they can inhibit glutamate receptors and
thereby decrease apoptosis in cortical neurons [71]. Both hexa(sulfobutyl)-fullerenes
and trimesic acid (TMA) fullerenes were shown to be effective in the treatment of
neurodegenerative illnesses 55, 56, thanks to their capacity to trap free radicals.
The neuronal degeneration caused by ROS has been shown to be mitigated by using
water-soluble derivatives, such as fullerenols and malonic acid fullerenes [72]. The
prevalence of neurodegenerative illnesses is increasing, and as a result, the physical
and social aspects of people’s lives suffer. This may be because people are living
longer and thus developing a systemic insufciency. By adopting delivery systems
based on fullerenes, the criticalities of the issue can be surmounted.
7.7 SUMMARY
Carbon, the most prevalent element in organic molecules, has been shown to occur
in two allotropes: diamond and graphite. Fullerenes, a third kind of carbon, were
discovered in 1985 by Smalley, Kroto, and Curl. In their study, a portion of solid
graphite was evaporated into plasma comprising ions and atoms by irradiating it with
a laser. Clusters with varying quantities of carbon atoms were synthesized as a consequence of the collision. It was discovered that clusters between 60 and 70 carbon
atoms predominate and that 60 atoms were present in the majority of clusters.
At the outset, the researchers faced difculties in synthesizing a sufcient quantity of fullerenes, and it took ve years for Krätschmer and Huffman (1990) and
Kroto etal. (1991) to establish alternative higher-yield sample preparation methodologies. The freshly discovered particle was given the architect Richard Buckminster
Fuller’s title since he designed the dome in 1967, which has the same form as the
carbon clusters.
The three researchers who invented fullerenes were awarded the 1996 Nobel Prize
in Chemistry because they sparked such fascination and enthusiasm among scientists
and researchers. The most prevalent fullerene, C
made up of 60 carbon atoms organized in 20 hexagons and 12 pentagons, giving it
the shape of a hollow sphere. It is a good candidate for electron transfer processes and
exhibits moderate reactions in the visible spectrum as well as substantial absorption
, was discovered in 1985 and is
60
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