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Challenges and
11
Opportunities
of Carbon-Based
Nanomaterials as
Nanocarriers
11.1 THE GLOBAL DEMAND FOR NANOPHARMACEUTICALS—
JOURNEY FROM LAB TO SHOPS
The worldwide nanomedicine market was worth $1.71billion in 2020 and is expected
to reach $4billion by 2030, growing at a compound annual growth rate (CAGR) of
9.2% between 2021 and 2030 [1]. In layman’s analogy, nanomedicine is the medical
subeld that uses information about nanotechnology to improve health. Nanomedicine is the application of nanoscale materials, such as biocompatible nanoparticles
and smart nanocarriers, which also includes the diagnosis, transport, sensing, and
actuation of therapeutics inside living organisms.
Nanomaterials have physicochemical properties that differ from their bulk chemical counterparts due to their minute size. Due to these qualities, new routes for pharmaceutical research and development have become available. There is a possibility
that the nano formulation’s physicochemical features will enable it to overcome biological barriers, toxicity, and persistence in the environment and the human body. In
the pharmaceutical sector, nanoparticles can be created from the top down or the bottom up. With the help of mechanical or chemical energy, top-down processes reduce
huge volumes of material to smaller quantities. On the other hand, the bottom-up
technique uses atomic or molecular species as the starting point for a chain reaction
that ultimately produces bigger precursor particles.
The path of a nanopharmaceutical from the laboratory to the market includes
research and development, preclinical testing, clinical trials, and regulatory approval.
After a nanopharmaceutical has been produced and proved safe and effective in animal research, it must undergo human clinical trials to establish its safety and efcacy
in a broader population. If the medicine is effective in these studies, it can be submitted for regulatory approval to the FDA in the United States or the European Medicines Agency (EMA) in Europe [2]. In contrast to conventional therapeutics, the early
and late stages of the development of therapeutical nanoparticles are fraught with
several obstacles. These issues are primarily linked to nanoparticles’ hierarchical and
heterogeneous morphology, which makes it such that even a seemingly minor change
286 DOI: 10.1201/9781003358114-11
287Challenges of Carbon-Based Nanomaterials as Nanocarriers
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in one aspect might signicantly affect the particle’s pharmacokinetics or therapeutic
efcacy. Common issues include, for example, the failure to maintain a tight particle
size distribution. For most applications, particles less than 200 nm are desirable. With
a broad normal distribution, the average particle size must be impractically small if
the population of particles bigger than 200 nm is to be restricted. Consequently, it is
desirable to use a manufacturing technique that results in a conned size distribution.
In addition, the nanoparticle’s experimental and production phases may provide
various unexpected challenges. In many instances, the synthesis techniques for making nanoparticles must be rethought entirely, as a methodology that is efcient in the
lab is ineffective in a factory. In a factory, the nanoparticle structural variation must
be lower, the production quantity must be signicantly large, and the synthesis must
be more sterile than in a laboratory. Even if a particle is functional, all these problems
may make its manufacture uneconomical. Due to the tendency of nanoparticles to
aggregate and degrade in solution over time, any commercially marketable particle
must be stable in both environments. Moreover, the difculty in establishing the toxicity of nanoparticles over a microscopic molecule offers additional regulatory challenges. Thus, the duration and cost of clinical testing are signicantly increased. Due
to these limitations, it is crucial to consider scalability and reproducibility from the
outset of the development process in order to avoid problems down the line [3]. The
average period for research and approval of a new medicine is about 12years, and
the average cost of development is over $2.6billion. One can agree that the process
of taking a nanopharmaceutical from the lab to stores may be lengthy and expensive.
Once a nanopharmaceutical has been authorized, it may be produced and supplied to pharmacies and other retail locations. However, the expense of research
and development, clinical trials, and regulatory approval can be considerable, making nanopharmaceuticals more expensive than conventional medications. As more
nanotechnology-based medications are created and authorized for use, the demand
for nanopharmaceuticals is anticipated to continue to increase in the future years.
Figure11.1 illustrates the phases of the development of nanotherapeutics [4].
FIGURE 11.1 Pathways by Which a Chemical Compound Is Developed into a Pharmaceutical. [Reprinted with permission from Etheridge et al. (2013)] [4].
288 Carbon-Based Nanocarriers for Drug Delivery
11.2 A GLIMPSE OF THE FUTURE FOR CARBON-BASED
NANOCARRIERS FOR DRUG DELIVERY
In the medical area, carbon-based materials have a restricted number of applications. Carbon nanomaterials (CNMs) are a remarkable innovation in nanotechnology that continues to make news in the scientic and technological sectors. Due to
their diversity, which includes carbon nanotubes (CNTs), graphene quantum dots
(GQDs), graphene oxide (GO), fullerene, carbon nanobers (CNFs), and carbon
sheets, CNMs are readily exploitable for biological purposes (CS) [5]. Figure11.2
shows the plethora of CNMs. Sumio Iijima discovered in 1991 that the carbon arc
discharge produced multiwall CNTs, and he and Donald Bethune were later able
to generate single-wall CNTs [6]. CNMs are carbon allotropes, but their nanoscale
dimensions imply a different structural structure. Graphene, fullerenes, carbon
bers, amorphous carbon, and carbon nano-onions are examples of CNMs. Unlike
carbon nanotubes and bers, graphene has a two-dimensional (2D) structure. CNM
has demonstrated promise in a variety of biological applications, including medication delivery, biosensors, cancer therapy, tissue engineering, disease and infection
detection, and diagnostic imaging [7]. CNM toxicity is still a problem, limiting its
biological use. CNM toxicity is inuenced by numerous factors, including the substance’s shape, size, and chemical composition, as well as the individuals’ susceptibility to the substance, the rate at which they ingest it, the rate at which their cells
absorb it, and the mechanism of cytoplasmic and nuclear interference. Due to adulteration, some CNMs may be hazardous. The addition of metal ions to CNM synthesis increases their cytotoxicity. Researchers have demonstrated that cancer cells
that consume CNMs perish due to DNA and lipid damage brought on by an increase
in reactive oxygen species (ROS). Exposure to graphene materials increases ROS,
FIGURE 11.2 The Various Kinds of Carbon Nanomaterials Available as Nanocarriers for
Administering Medication. [Reprinted with permission from Brindhadevi et al. (2023)] [5].
289Challenges of Carbon-Based Nanomaterials as Nanocarriers
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which affects macrophage function, destroys mitochondrial membranes, and eventually results in cell death [8].
The solubility, safety, and biodegradability of CNMs can be enhanced by modifying their surface functionalization. The slower clearance and extended retention
in the body improve the efcacy of pharmaceutical delivery. Cationic and anionic
functionalization can increase the toxicity of CNMs beyond that of unfunctionalized
CNMs when added to CNMs. It has been claimed that the surface functionalization
of amino acids, medications, small molecules, peptides, and proteins can enhance
the solubility and efciency of CNMs. Various interaction mechanisms, including
ionic, covalent, and van der Waal forces, are employed to tag target-specic molecules on CNMs [5]. This modication results in the transmission of several traits and
characteristics with potential medical applications. Contact with active compounds
or drugs can modify the surface functional groups required for drug loading and
grafting onto the appropriate morphologies of CNMs. To improve their physical,
chemical, and biological properties for usage in biomedical applications, it is imperative to explore the unique characteristics of CNM.
Furthermore, with its uncontrolled release, the traditional pill has been replaced
by medication delivery techniques with greater bioavailability and fewer side effects.
Ongoing research is being conducted on more precise, controllable, and user-friendly
ways of pharmaceutical administration. At the forefront of research are drug delivery methods for future viruses, safety, symbiotic delivery systems, gender-sensitive
delivery systems, affordability, greener drug delivery systems, and systems that achieve
unmet clinical needs.
11.2.1 oVercoming The BlooD-Brain Barrier
The blood-brain barrier (BBB) is a selectively permeable membrane that acts as a
barrier between the bloodstream and the central nervous system, protecting the brain
from harmful substances. However, this barrier also makes it difcult for drugs to
reach the brain, limiting the effectiveness of many treatments for neurological diseases. In terms of years of healthy life lost due to disability, neurological disorders
rank #1 globally. Glioblastoma multiforme is among the deadliest neoplasms and
is one of the rare diseases that may end in death shortly after diagnosis. Asia has
the most fatality rate, with a median survival time of seven to 15 months following
diagnosis [9]. The traditional and initial line of defense against brain tumors is surgical resection. However, glioblastoma is distinctive in that it inltrates and develops
aggressively in the blood arteries of the surrounding brain parenchyma, making complete surgical ablation difcult. Aging populations are disproportionately affected by
neurological disorders. Neurodegenerative diseases, such as dementia, epilepsy, and
other seizure-inducing disorders, Parkinson’s disease and other movement disorders,
mental issues, stroke, and transient ischemic attack, necessitate immediate study into
therapies and prevention [10].
The limited solubility of neurotherapeutics via the oral route and their bioavailability being hindered by two barriers, the BBB and the blood-cerebrospinal uid
barrier (BCSF), signicantly restrict the treatment and management options for neurological illnesses. The blood-brain barrier divides the brain’s circulatory system
290 Carbon-Based Nanocarriers for Drug Delivery
from its nerve tissues, making it extraordinarily difcult to deliver therapeutic agents
to the brain’s site of action. In chemotherapy, drugs are used to induce cell death in
brain cancer patients; however, drug delivery is hindered by several factors, including
tumor heterogeneity, hypoxic tumor environment, the presence of glioma stem cells,
aberrant signaling pathways, and most importantly, the existence of the BBB, resulting in high recurrence rates, overall resistance to therapy, and devastating neurological deterioration. In the past two decades, advanced intelligent drug delivery systems
have enabled more effective treatment of neurological disorders and malignancies
such as schizophrenia, migraine, Parkinson’s, Alzheimer’s, and brain tumors. Nanotherapeutics is an emerging eld that aims to overcome the BBB by using nanoscale
particles to deliver drugs directly to the brain. This approach has shown promising
results in preclinical studies, as the small size of these particles allows them to bypass
the BBB and target specic cells within the brain. Recently, nanoscale drug carriers
have been utilized to boost the therapeutic effectiveness of therapeutic medications
with no or little side effects, as listed in Table11.1 [9]. The distribution of drugs to the
brain presents several obstacles. However, many pharmaceutical nanocarriers may be
utilized to develop successful drug delivery systems with desirable properties.
Enclosing the medicinal substance in the nanocarrier can improve its solubility
and stability. Nanocarriers containing a chemical capable of interacting with the
targeted receptor expressed on the targeted cell’s surface can inhibit cancer cells
from absorbing the drug [11]. Due to their new physicochemical properties and
lower toxicity, carbon nano-onions (CNOs) have shown promise [9,12]. CNOs have a
TABLE 11.1
List of Medications Administered with Nanocarriers or Functionalized
Nanocarriers. [Reprinted with permission from Majumder et al. (2021)] [9].
Drug Nanocarrier Functionalization Uses
Doxorubicin SWCNT PEG Reduced toxicity
MWCNT Folic acid Active targeting
Human serum albumin Amino/acid group Antineoplastic
PLLA-b-PEG Folic acid Solid tumors
Polymer-lipid hybrid Lipid
Poly (DEAP-Lys)-b-PEG -
b-PLLA
Paclitaxel SWCNT PEG Increased circulation period
Trimyristin Sterically stabilized Ovarian, lung, and breast cancer
PEG-PE Lipid Various cancers
Cisplatin SWCNT Reduced toxicity
Methotrexate MWCNT Folic acid Controlled toxicity
Estrogen PLGA Alendronate Bone-osteoporosis
Oligonucleotide PEG or PE particles Transferrin Brain-gene
siRNA PE RGD peptides Vasculature cancer
Retinoic acid PLA Galactose Hepatocytes
Poly(lysine)
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multilayered fullerene structure. Since nanoparticles (NPs) of range 20 nm or less are
permitted to pass through it, the size of CNOs between 1 and 15 nm promotes barrier
permeability mainly through the transient opening of tight junctions or fusing with
membrane bilayers and ion-pairing [13]. The BBB is the most signicant barrier in
brain-targeted delivery because it restricts the bioaccumulation of drugs at the target
site. The BBB comprises several cell types: neurons, astrocytes, pericytes, and brain
capillary endothelial cells [14].
Nanomedicines with high lipophilicity are ideal for drug administration to the
brain because they can more readily traverse the BBB. Because of their unique
optical, thermal, magnetic, and physicochemical properties—including their tiny
size, huge specic surface area, and high chemical reactivity—materials with sizes
between 10 nm and 100 nm are now the focus of BBB-crossing applications [15].
Another example is magnetic nanoparticles, which can be guided through the BBB
using a magnetic eld. Under the inuence of a magnetic eld, magnetic nanoparticles (MNPs) can enter human cells and tissues, making them useful for diagnostic purposes. These MNPs may be directed to and kept in diseased tissue with an
external magnetic eld, allowing for the differentiation of cancerous cells from normal cells in the body [16]. In medicine, polymer-coated iron oxide nanoparticles
are employed for a variety of applications, including medication administration,
magnetic resonance imaging (MRI), and hyperthermia due to their nontoxicity and
biocompatibility. They do better than metallic inorganic nanoparticles like cobalt,
nickel, and others. Magnetic susceptibility (χ) is dened as the ratio of induced magnetization (M) to an applied magnetic eld (H) and is used to categorize the magnetic
characteristics of various materials. Those with no magnetic moment and a slight
negative magnetic susceptibility are called diamagnetic.
In contrast, those with a random or parallel magnetic moment and a slight negative magnetic susceptibility are called paramagnetic, and those with a magnetic
moment parallel to H and a signicant negative magnetic susceptibility are called
ferromagnetic or ferrimagnetic [17]. After being functionalized with the polymer
coating, MNPs can efciently load additional pharmaceuticals due to the presence of
multiple functional groups on the polymer surface. Additionally, this increases the
half-life of MNPs, which decreases their toxicity to cells. Surface functionalization
can utilize natural and synthetic polymers, lipid molecules, and functional ligands
for selective or receptor-mediated targeting [18]. This method has been tested in preclinical studies for treating brain tumors and has shown promising drug delivery and
efcacy results.
In conclusion, nanotherapeutics can revolutionize the treatment of neurological
diseases by allowing drugs to bypass the BBB and directly target the brain. While
further research is needed to fully realize this approach’s potential, the results have
been promising, and nanotherapeutics may play a vital role in the future of neurological disease treatment.
11.2.2 aDVances in ocUlar Therapies
The human eye consists of two segments: the anterior and posterior segments. The
cornea, conjunctiva, aqueous chamber, iris, ciliary body, and lens comprise the
292 Carbon-Based Nanocarriers for Drug Delivery
anterior section of the eye, also known as the anterior segment. Because the front of
the eye is easily accessible, eyedrops administered topically are standard therapy for
anterior eye diseases. Due to the corneal barrier, quick tear lm turnover, and rapid
tear drainage, topical eyedrops are unreliable due to their poor ocular absorption.
The posterior region of the eye consists of the vitreous body, retina, and choroid [19].
Eyedrop-delivered drugs have a very low concentration in the retina and vitreous
humor because they must travel a great distance and overcome many ocular obstacles to reach the back of the eye. Due to the presence of the blood-retinal barrier
(BRB), medications cannot be successfully transported to the eye via the systemic
route; instead, very high doses are required, which might cause undesired systemic
side effects. As they may transport drugs directly to the back of the eye, vitreous
humor and intravitreal (IVT) injections are now frequently employed in clinics to
treat acute eye diseases. Therapeutic success needs frequent IVT injections because
vitreous humor turnover allows quick clearance of unutilized medications following
IVT injections. It has been demonstrated that patients who require frequent IVF
injections may be less cooperative with their therapy, pay larger nancial expenditures, and be at increased risk for injection-related complications [20]. To reduce
the strain on patients and improve treatment efcacy, IVT drug delivery devices
with extended drug release characteristics are required. Subconjunctival (SCT), subtenon, and peribulbar injections are examples of periocular delivery that are less
invasive than IVT injections but can still carry drugs to the back of the eye. To reach
the retina and vitreous, medications must rst pass through the sclera, choroid, and
retinal pigment epithelium (RPE) of the eye. Due to these drug transport obstacles
in the ocular tissue layers, effective drug concentrations cannot be delivered to the
retina following periocular administration [21]. Suprachoroidal administration is a
promising method for delivering drugs to the back of the eye since it circumvents the
sclera, a signicant diffusion barrier encountered by periocular drug delivery [22].
Suprachoroidal medicine delivery poses the risk of retinal hemorrhage and detachment, necessitating the use of specialist equipment (such as microneedles) to ensure
the drug reaches the retina in a safe and regulated way [20].
Others may increase the solubility of hydrophobic medications in an aqueous
solution, offer prolonged drug release with less toxicity and greater efcacy, increase
drug retention duration, and enhance drug penetration through ocular barriers.
Nanomedicines found for ocular drug administration include liposomes, polymeric
nanoparticles, micelles, and dendrimers, to name a few. Liposomes’ aqueous core
comprises phospholipids, cholesterol, and lipid-conjugated polymers. The aqueous
core of liposomes can be loaded with hydrophilic drugs, whereas lipid bilayers can
be loaded with lipophilic drugs [23]. It is possible to modify polymeric nanoparticles
to store a signicant number of drugs for prolonged, controlled release. Dendrimers
are spherical, nanostructured (3–20 nm) polymers with minimal polydispersity. The
functional groups on the surface of dendrimers might be utilized to attach pharmaceuticals, or the medications could be enclosed within the dendrimer core. Dendrimers’ manufacturing, surface chemistry, and conjugation strategy can be modied
to maximize drug loading and release [24]. Micelles are self-assembled spherical
vesicles with a hydrophilic corona and a hydrophobic core that can solubilize and
stabilize hydrophobic drugs [25].
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Nanomedicine for the eye has been created using cutting-edge nanofabrication
techniques such as particle replication in a non-wetting template (PRINT) and the
hydrogel template approach [26,27]. The PRINT process is a nanofabrication method
that uses roll-to-roll manufacturing to produce monodispersed NPs and microparticles of a specic size, shape, and modulus [26]. Using PRINT technology to create NPs requires three steps: rst, constructing micro molds with precise micro- or
nano-cavities; second, molding therapeutic substances into the cavities; and nally,
releasing NPs from the mold after they have hardened. Manufacturing particles with
repeatable form, size, and surface modication on a large scale using a continuous process, the physiochemical properties of PRINT particles could be modied
by modifying matrix composition or post-functionalization [20]. PRINT has been
shown to function with a variety of biocompatible polymers and pharmaceuticals,
such as nucleic acids, proteins, and antibodies. For controlled drug delivery to the
eye, PRINT technology has produced ocular formulations such as subconjunctival
(SCT) implants, intracameral (IC) implants, intravitreal (IVT) implants, nano- and
micro-suspensions, and other similar forms. AR13503, a potent inhibitor of Rho
kinase and protein kinase C (PKC), may one day be used to treat retinal neovascularization. The biodegradable polymers PLGA/PDLA/poly(ester amide) (PEA) were
produced into a rod shape and appropriately sized for injection with a 27 gauge needle utilizing PRINT technology (80). AR13503 implants utilizing PRINT technology
demonstrated in-vitro drug release for more than 60 days. In 2019, clinical trials for
the PRINT-based AR13503 implant to treat diabetic macular edema (DME) and wet
age-related macular degeneration (AMD) will commence. The PRINT method has
been proven effective for the GMP production of kilogram quantities of NPs [20].
The hydrogel template method permits the production of vast quantities of uniform
nanoparticles and microparticles, which are then transported by the template itself.
Nanowafers are ultrathin, translucent lenses that contain nano-drug reservoirs. They
are fabricated utilizing hydrogel template technology. Generation of the PVA template
with well-fabricated arrays, e-beam lithography was used to form a pattern on a silicon
wafer, and then PVA solution was poured over the pattern. Nanowafers were produced
by pouring solutions of medicinal substances into a PVA mold. By adjusting the capacity of the drug reservoirs, drug loading and particle size may be regulated. The ocular
surface can be implanted directly with nanowafers for extended drug release. In contrast to standard contact lenses, which must be removed to avoid bacterial infection,
nanowafers are made from dissolvable PVA and may dissolve away automatically.
11.2.3 improVemenTs in cancer TreaTmenTs
In the global South, cancer has emerged as the major cause of mortality. Carbon
nanoparticles are at the forefront as an efcient medicine delivery technology for
cancer diagnosis and treatment. CNMs are the ideal delivery mode for transferring
pharmaceutical substances to the site of action, avoiding degradation of the molecules loaded. In addition, it helps retain the potency of the molecule at its site of
action while simultaneously reducing its off-target effect and boosting its overall
efcacy. CNMs of many types release anticancer medicines in a regulated and sustained manner to prevent the multiplication of cancer cells. CNMs have been loaded
294 Carbon-Based Nanocarriers for Drug Delivery
with several anticancer drugs, including doxorubicin (DOX), betulinic acid (BA),
methotrexate (MTX), gemcitabine (GEM), etoposide (ETO), paclitaxel (PTX), chelerythrine (CPT), camptothecin (CPT), carboplatin (CPM), cisplatin (CIS), platinum
(II), and platinum (IV) [28].
Due to their toxicity and insolubility, only graphene sheets, carbon quantum dots,
and carbon nanotubes have been effectively exploited for cancer treatment and diagnostics. These CNMs are less toxic than other metallic nanoparticles and may be
functionalized with a variety of ligands to facilitate the conjugation of anticancer
drugs within or on their structure. They used a range of polymers, including PEG
and chitosan, ligand-specic attachment sites readily accessible by tumor cells that
have been functionalized. The drug doxorubicin can be bound to graphene through
hydrogen bonds to oxygenated functional groups, allowing for time-controlled drug
release. Genetic material may be adsorbed onto graphene through interaction between
the nucleic acid base and the polyaromatic basal plane of graphene nanomaterials.
This enables the transfer of single-stranded nucleic acid resistant to destruction by
variables like temperature, pH, and enzymes.
There was a developing concern with the elimination or toxicity of CNMs, but
this issue has been rectied, thanks to the use of organic components in the synthesis
of CNMs. If research into boosting target specicity and pharmaceutical loading
capacity is conducted, it is possible to construct treatment programs with a longer
duration. Recent research has demonstrated that CNMs carrying siRNA effectively
destroy cancer cells. More effective delivery methods, such as CQDs, may be developed with the help of the research and development of innovative anticancer drugs
and agents. In addition, it is possible to obtain 100% efcacy against cancer cells by
loading numerous drugs onto a single CNM [5].
11.3 VIRAL NANOPARTICLES AS DRUG DELIVERY SYSTEMS
The growth of nanotechnology over the last several decades has opened new opportunities in the world of medical research, notably in the area of medicine administration. Traditional drug carriers have been constructed from liposomes and lipids,
synthetic and natural polymers, and inorganic nanoparticles [29]. Nanoparticles for
medication delivery must be biocompatible, biodegradable, and have a low degree of
toxicity to have a substantial therapeutic impact [30]. However, the toxicity and low
delivery effectiveness of a number of synthetic carriers demand the development and
deployment of alternate delivery techniques. There is an urgent need to introduce
novel pharmaceutical delivery strategies to the research and development pipeline
because there is no “perfect solution.” Protein-based nanoparticles, such as protein
cages and viruses, are examples of an emerging class of novel drug carriers [31].
Protein cages are instances of self-assembled supramolecular structures composed of
their component protein monomers. Their constituent elements are not infectious by
denition. Virus-like particles (VLPs) are analogous, but they vary in that they are
created by carefully assembling the viral coat proteins. Viruses are sturdy structures
that can withstand external forces and resist degeneration, but they are also sensitive
to signals in their surrounding cellular environment, allowing them to release their
genome when instructed to do so.
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Within the category of viruses, two subcategories can be identied. These are
known as VLPs and viral nanoparticles (VNPs). It is widely believed that VLPs, the
genome-free equivalents of VNPs, do not induce infection. Due to the possibility that
viral genomes may or may not be present, they may impart unique immunostimulatory patterns. This study examines VLP and VNP plant viruses in addition to bacteriophages. In some situations, we also explore the application of different protein
cages and highlight a few viral nanotechnologies for mammalian cells. Since the
self-assembly of repetitive protein subunits forms viral capsids, they possess a high
degree of polyvalence. Viruses may infect a variety of cell types. Plant viruses are typically non-enveloped organisms that can have a spherical/icosahedral or lamentous/
tubular shape. Plant viruses are also capable of morphing over time. Viruses are considered natural nucleic acid carriers because they protect and deliver their payload, the
principal characteristic exploited for medication distribution [32,33]. Infusion, encapsulation, absorption, or conjugation of drug cargo to the inner and external surfaces
of the coat protein interfaces, combinations of chemical procedures, and attachment
to the different functional groups given by the protein structure can be utilized. These
operations can occur on either side of the protein. This versatility enables a vast array
of possibilities, including reversible binding of active chemicals, protection inside proteinaceous matrices, and selective targeting to the site where the action will occur [29].
Due to their morphological uniformity, biocompatibility, water solubility, facile
functionalization, and high absorption efciency, natural delivery carriers, and VNPbased carriers, in particular, provide a number of signicant advantages. Nanomedical approaches for drug delivery or imaging must also utilize biological properties to
construct clever nanosized cages with high stability, appropriate pharmacokinetics,
cell targeting, and effective cell penetration. Since plant viruses seldom exhibit tissue
tropisms, secondary functions such as cell surface receptor binding, targeting ability,
membrane crossing, and nuclear penetration might be added into a nanoparticle formulation (synthetic or natural) [34].
Even though no plant- or bacteriophage-based nanomedicine has yet been
approved for clinical use, several systems are now undergoing investigation, and
a few are on the verge of entering translational development. Among the plant
VLP and VNP-based nanotechnology platforms being explored for varied nanomedical applications are tobacco mosaic virus (TMV), cowpea mosaic virus (CPMV),
cowpea chlorotic mottle virus (CCMV), physalis mottle virus (PhMV), and potato
virus X (PVX). Notable bacteriophages include MS2, P22, Q, and M13. One may
encounter viruses ranging in length from less than 30 nm to more than 1 micron, as
illustrated in Figure11.3 [29]. Utilizing biochemistry and guided evolution, viral
nanocarriers for medication delivery, imaging, and theranostic applications have been
produced, and their use has been growing. In this chapter, we discuss the diagnostic and therapeutic potential of VNPs and VLPs in a variety of biomedical settings,
including antimicrobial, cancer, protein/peptide, and gene therapies; monotherapy
and combination therapies against cancer; vaccines against infectious diseases, cancer, and other diseases; nanocarriers for imaging modalities; and theranostics with
photothermal therapy (PTT).
Currently, chemotherapy is the treatment of choice for cancer. However, maximumtolerated pharmaceutical dosages are frequently employed in cancer therapy, which
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