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Graphene Quantum Dots-based Nanomaterials for Drug Delivery 375
Fig.12.7. M To load the chemotherapeutic medication doxorubicin (Dox) onto sEVs. D-CysGQDs. a A schematic shows how D-Cys-GQDs make loading with Dox easier for sEVs. b Reducing
efficiency and fluorescent spectra (max = 360 nm) were used to characterize the direct addition
of Dox (200 M) onto the D-Cys-GQDs (7.5–22). Using a confocal microscope at room temperature, c a comparison is made between the loading methods of D-Cys-GQDs (15 M) and ultrasound
treatment for Dox (200 M for both tactics). d Chiral GQDs improve the efficiency with which Dox
is loaded into sEVs. Scale bars, 10 m e Confocal images showing in vitro 3T3 cell uptake of free
Dox and sEVs-Dox (loaded ratio 15 M/200 M, D-Cys-GQDs/Dox) and f viability of cell measured
using the CCK-8 test. Reproduced with permission from the American Chemical Society [58]
cell viability of all samples. (Fig. 12.7f) was equivalent to sEVs-Dox (HepG2: 44.2
9.2% and HeLa: 27.4 6.5% cell proliferation inhibition) [58].
9 Toxicology Concern of GQDs-Based Nanomaterials
for Drug Delivery
Because of the risk of accumulation and biological targeting with other particles
that alter the properties of the infused nanoparticles and interfere with cell activity,
using quantum dots as a therapeutic agent is not yet practical. GQDs synthesized
using various approaches, geometrical parameters, and surface groups should be
376 M. Emamul Kabir et al.
tested for their biodistribution, organ accumulation, and genotoxicity. Nanofabrication techniques and surface features such as surface charges, nanosizes, functional groups, contaminants, and element doping can contribute to GQD toxicity
[58, 76, 77]. Previous research has shown that the poisonousness of GQDs relies
on concentration; nonetheless, cells may endure very curt concentrations of GQDs,
making their use in biomedical applications unrealistic. For instance, if the inten-
−1
sity of GQD is enhanced from 50 g/mL
mg/mL, cell viability is cut in half [78].
GQDs’ concentration-dependent ROS production increases their toxicity. The toxicity of GQDs stems from their size rather than their concentration. The toxicity of
GQDs varies with their size and form. For both in vivo/vitro cytotoxicity, GQDs were
shown to have a maximum side edge size of 50 nm [79]. Setting the quantitative cytotoxicity barrier for GQDs is extremely difficult because their toxicity changes over
time [80]. A-GQDs (200 g/mL) can generate DNA breaking via H-attachment and
stacking [81], while N-GQDs can buckle the configuration of lipid droplets, disorder
the redox-sensitive technique, disturb calcium homeostasis, and cause ferroptosis.
The promise of GQDs in medication delivery has led to much research into their
toxicity in biological systems. Researchers administered numerous doses to model
clinical drug testing to further understand the effects of PEG-modified GQDs in vivo
[82]. No clear evidence of GQDs-PEG toxicity was found. Cancer drugs like Dox and
Docetaxel bypass the cell membrane and cause cytotoxicity by restricting replication
and translation, preventing DNA and RNA synthesis [38]. These medicines break
DNA by intercalating between two base pairs. They become radicals inside cells and
can cleave DNA. Because of their non-specificity and systemic noxiousness, these
medicines have limited drug solubility and severe side effects. The nano-drug carrier
bypasses internalization mechanisms that resist anti-cancer drugs to reach the nuclei.
They kill tumor cells by entering the cell and traveling to the nucleus via clathrinmediated, caveolae-mediated endocytosis, or receptor-mediated. GQD-DOX conjugation enhances cytotoxicity by targeting drug transport and DNA cleavage [46].
Table 12.3 summerized the toxicity behavior of different GQDs-based nanomaterials.
10 Challenges and Future Perspectives
GQDs have been acquired to deliver drug vehicles in nanomedicine studies efficiently.
Their physicochemical and biochemical properties guarantee this. Despite years of
study, GQDs are only just becoming mainstream in therapeutic applications. Due to
concerns over in vivo toxicity and long-term biodegradability, carbon-based nanomaterials like GQDs are limited to studying cells and small animals in the lab. Due to
these concerns, the use of quantum dots in nano DDS-based pharmaceuticals has been
halted [37]. Toxicities and a lack of contradicting data have prevented GQDs from
being widely used as pharmaceutical delivery vehicles. GQD, a recently discovered
nanomaterial, has limitless applications in medication administration. GQDs that
extend therapeutic windows and efficiently transfer medications to the target site
with minimal systemic toxicity should be the primary focus of development rather
Graphene Quantum Dots-based Nanomaterials for Drug Delivery 377
Table 12.3 Toxicity of different GQDs-based nanomaterials. Adapted and reproduced with
permission form ACS [15]
Materials Cells Assay Concentration
GQDs-PEG A549, HeLa WST-1, LDH 160, 640 24 > 95,
fGQDs HFF MTT 40, 200 24 >8,>30[83]
GQDs A549 MTT 100 24 80 [11]
GQDs MGC-803,
MCF-7
mGQDs C6, A549, MTT 200 24 >80 [85]
N-GQDs HeLa CCK-8 400 24 >80 [86]
cGQDs KB,A549 MDCK,
MDA-MB231
GQDs HeLa CCK-8 200 24 80 [88]
mGQDs HeLa,
MCF-10A,MCF-7
HGQDs HUVEC CCK-8 500 48 >80 [90]
mGQDs HeLa MTT 8000 24 ∼50 [78]
MTT 400 24 ∼70 [84]
MTT, LDH 500 21d/24 >95 [87]
MTT 2000 24 ∼97 [89]
(μg/mL)
Incubation
time (h)
Cell
viability
%
∼85
Reference
[82]
than their synthesis, problems, and expensive separation. In addition, a Microfluidic
environment should be properly attributed in laboratory settings to mimic the biological process in drug delivery experiments to flow effectively and pressure control
[91–93] in microchannel as more shear stress may threaten cell viability. Besides,
this nano-drug delivery method must advance locally and systemically across various
cell types and tissue categories. The target site-GQD interaction might be studied in
greater depth with the help of improved molecular-levelunderlying forces study using
models to appreciate small-scale difficulties [47]. Since GQDs can traverse biological
barriers like the Blood–Brain Obstacle despite their diminutive size, they have been
introduced to nano-neurology. However, more research is required to address toxicity concerns. Inflammation is mitigated using GQDs to restrain immune cells. When
treating autoimmune diseases, such as inflammatory bowel disease [94], GQDs can
be a viable option.
Drug delivery is enhanced because of its malleable core, tailored architecture,
and bonding (π-stacking), making it superior to other Nano-DDS. Due to their great
biocompatibility and minimal systemic toxicity, GQD-based drug delivery methods
may become more practical in the future. Gene delivery and therapy can benefit
from viral vectors because they convey genetic material to their intended recipients.
Immunogenicity problems with viral vectors are resolved with GQDs, allowing them
to be used in clinical settings. They are excellent candidates for traceable transfection
vectors to transfer genes in-vitro/vivo because of their tiny size, capacity to bypass
living barriers, extraordinary constancy, and luminescence GQDs can load nucleic
378 M. Emamul Kabir et al.
acid (RNA, DNA) and act as a non-viral gene vector by conjugating motioning
molecules and cationic polymers in the basal surface. The GQD-DDS has a functionalized component that safeguards drug transport in the mouth from acidic environments [95]. GQDs will soon dominate pharmaceutical, biomedical, and related
industries as they are studied and documented in depth.
11 Conclusions
GQDs-based DDS increase drug loading, targeting, and efficacy in targeted cancer
therapy. Nanoshells, liposomes, dendrimers, superparamagnetic, nucleic acid-based
nanoparticles and CNTs, target physiologically active fractions into living systems.
Next-generation GQDs have biological potential. These materials can carry medications well. GQDs can multimodally conjugate like graphene and GO, making
them potential cancer cell therapy and surveillance carriers. Their structure boosts
chemotherapeutic efficacy. Nanostructured materials having active units can be
synthesized using several methods. Synthesis mode can modify GQD functions based
on output. GQD energy bandgaps affect electroluminescence, photoluminescence,
and absorption.
GQD knowledge gaps must be filled to use these novel nanomaterials. Recent
research has revealed the promise of these nanocarriers in drug delivery applications.
However, they still have limitations in targeted cancer therapy. GQD’s research for
drug delivery applications are still incubating. Therefore, many nanomaterial functions are unknown. GQDs model drugs permeating the lipid membrane in nanoseconds with minimal cell membrane deformation. These findings support GQD-based
drug delivery system molecular design and application. GQDs can deliver genes,
peptides, and non-anticancer drugs to specific locations. Despite GQDs’ enhanced
biocompatibility, animal models are needed to examine their long-term toxicity and
mechanisms of immunological, reproductive, and neurological system effects. Characterization standards are essential since GQDs’ physicochemical characteristics
vary by manufacture. Systematic studies are needed since GQD size impacts toxicity, surface functionalization, and biological carrier crossing. GQD research may
improve biological efficacy and address GQD-based drug delivery system design
and manufacturing difficulties.
Conflict of Interest Statement The authors have declared no conflict of interest.
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