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Файл:Ординатура / Хирургия / Библиотека им академика М.И. Перельмана / Книга_5362_Библиотеки_им_академика_М_И_Перельмана.pdf
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- •Carbon Based Nanomaterials for Drug Delivery
- •Preface
- •Acknowledgements
- •Contents
- •Editor and Contributors
- •Abbreviations
- •1.2 Market Statistics
- •Carbon-Based Nanomaterials: An Overview
- •1. Introduction
- •1.1 Evolution of Carbon-Based Nanomaterials
- •2. Carbon-Based Nanostructures
- •2.1 Fullerene
- •2.2 Carbon Nanotubes (CNTs)
- •2.4 Graphene
- •2.5 Nanodiamonds (NDs)
- •2.6 Nano-Onions (CNOs)
- •2.7 Nanohorns (CNHs)
- •2.8 Carbon Dots (CDs)
- •2.9 Nanoporous Activated Carbon
- •3. Synthesis Techniques
- •4. Properties of Carbon-Based Nanomaterials
- •4.1 Physicochemical Properties
- •4.2 Thermal Properties
- •4.3 Mechanical Properties
- •4.4 Optoelectronic Properties
- •4.5 Antimicrobial Properties
- •4.6 Biological Properties
- •5. Applications of Carbon-Based Nanomaterials
- •5.1 Environmental Remediation
- •5.2 Agriculture
- •5.3 Biofuel
- •5.4 Energy Storage
- •5.5 Biomedical Applications
- •6. Challenges and Future Perspectives
- •7. Concluding Remarks
- •References
- •Carbon-Based Nanostructured Materials: Designing, Properties and Applications
- •1. Introduction
- •2.1 Zero-Dimensional Carbon-Based Nanostructures (0D)
- •2.2 One-Dimensional Carbon-Based Nanostructures
- •2.3 Two-Dimensional (2D) Carbon-Based Nanostructures
- •2.4 Three-Dimensional (3D) Carbon-Based Nanostructures
- •3.1 Chemical Vapor Deposition
- •3.2 Hydrothermal and Solvothermal Techniques
- •3.3 Microwave-Assisted Technique
- •3.4 Chemical Oxidation Synthesis
- •4. Properties of Carbon-Based Nanostructured Materials
- •4.1 Thermal Properties
- •4.2 Mechanical Properties
- •4.3 Optoelectronic Properties
- •4.4 Antimicrobial Properties
- •4.5 Biological Properties
- •5. Applications of Carbon-Based Nanostructured Materials
- •5.2 Antibacterial and Antiviral Applications
- •5.3 Theragnostic
- •5.4 Wound Healing
- •5.5 Tissue Engineering
- •5.6 Drug Delivery
- •5.7 Biosensing
- •6. Challenges and Future Perspectives
- •7. Concluding Remarks
- •References
- •Drug Delivery System and Technologies
- •1. Introduction
- •2. Drug Delivery System
- •2.1 Conventional Drug Delivery System
- •2.2 Advanced Drug Delivery System
- •2.3 Controlled and Sustainable Drug Delivery System
- •3. Drug Delivery Technologies
- •3.1 Active and Passive Drug Delivery
- •3.2 Smart Drug Delivery
- •3.3 Intravenous and Extravaneous Drug Delivery
- •3.4 Various Types of Delivery Technologies
- •4. Challenges and Future Perspectives
- •5. Conclusion
- •References
- •Carbon-Based Nanomaterials for Drug Delivery: Past, Present, Future Directions
- •1. Introduction
- •3. Current Status in Drug Delivery by CNMs
- •3.1 Graphene-Based Nanomaterials in Drug Delivery
- •3.4 Nanodiamond Based Drug Delivery Systems
- •3.5 Nano-Onions in Drug Delivery
- •3.6 Nanohorns in Drug Delivery
- •3.7 Fullerene in Drug Delivery
- •4. Challenges and Future Perspective
- •5. Conclusions
- •References
- •Carbon Nanomaterial-Incorporated Supramolecular Drug Delivery
- •1. Introduction
- •2. Different Carbon Nanomaterials in Drug Delivery
- •2.1 Carbon Nanotubes (CNTs)
- •2.3 Graphene
- •2.4 Carbon Quantum Dots
- •2.5 Fullerene
- •2.6 Carbon Nanohorns
- •2.7 Carbon Nano-Onions
- •2.8 Nano-Diamond
- •3. Supramolecular Chemistry in Drug Delivery
- •3.1 Principles of Supramolecular Chemistry
- •3.3 Applications of Supramolecular Biomaterials
- •4. Carbon Nanomaterial-Incorporated Supramolecular Drug Delivery
- •5.1 Cyclodextrins
- •5.2 Calixarenes
- •5.3 Cucurbituril
- •5.4 Pillarenes
- •5.5 Crown Ether
- •6. Toxicity Concerns of Carbon Nanomaterials
- •7. Improving the Effectiveness of Nanoparticle Systems
- •8. Future of Nanomedicine
- •9.1 Challenges
- •9.2 Future Perspectives and Opportunities
- •9.3 Conclusions
- •References
- •Carbon Nanomaterial-Based Polymeric Nanocomposites for Drug Delivery
- •1. Introduction
- •2.1 Carbon Quantum Dot-Based Polymer Nanocomposite
- •2.2 Carbon Nanotube-Based Polymer Nanocomposite
- •2.3 Graphene Quantum Dot-Based Polymer Nanocomposite
- •2.5 Fullerene-Based Polymer Nanocomposite
- •2.6 Nanodiamond-Based Polymer Nanocomposite
- •3. Drug Delivery Systems Using Carbon Nanomaterial
- •3.1 Anticancer Drug Delivery
- •3.3 Infectious Disease Drug Delivery
- •3.4 Topical Drug Delivery
- •3.5 Brain Drug Delivery
- •3.6 Oral Drug Delivery
- •4. Challenge and Future Perspectives
- •5. Conclusion
- •References
- •Carbon Nanomaterial-Incorporated Polysaccharide-Based Nanocomposite for Drug Delivery
- •1. Introduction
- •1.1 Drug Delivery
- •1.2 Carbon Nanomaterials
- •1.3 Polysaccharide-Based Nanocomposite
- •2.1 CN-Incorporated Alginate-Based Nanocomposite
- •2.2 CN-Incorporated Cellulose-Based Nanocomposite
- •2.3 CN-Incorporated Chitosan-Based Nanocomposite
- •2.4 CN-Incorporated Dextran-Based Nanocomposite
- •2.5 CN-Incorporated Hyaluronic Acid-Based Nanocomposite
- •2.6 CN-Incorporated Starch-Based Nanocomposite
- •2.7 CN-Incorporated Pectin-Based Nanocomposite
- •2.8 CN-Incorporated Guar Gum-Based Nanocomposite
- •2.9 CN-Incorporated Agarose-Based Nanocomposite
- •2.10 CN-Incorporated Carrageenan-Based Nanocomposite
- •2.11 CN-Incorporated Glucomannan-Based Nanocomposite
- •3. Challenges and Future Prospective
- •4. Concluding Remarks
- •References
- •Graphene-Based Nanomaterials for Drug Delivery
- •1. Introduction
- •1.1 Challenges in Conventional Drug Delivery Systems
- •1.2 Overview of Nanomaterials for Drug Delivery
- •1.3 Role of Graphene-Based Nanomaterials in Drug Delivery
- •2. Synthesis of Graphene
- •2.1 Chemical Reduction Method
- •2.2 Thermal Reduction
- •2.3 Electrochemical Reduction
- •2.4 Chemical Vapor Deposition Method
- •2.5 Mechanical Exfoliation
- •2.6 Epitaxial Growth Method
- •2.7 Growth in Solvothermal and Hydrothermal Systems
- •2.8 Electrochemical Deposition
- •3. Types of Graphene-Based Materials
- •3.1 Graphene Quantum Dots, (GQDs)
- •3.2 Graphene Oxide (GO)
- •3.3 Graphene Nanoribbons (GNRs)
- •3.4 Oxidized Graphene Nanoribbons
- •4. Graphene Functionalized Materials for Drug Delivery
- •4.1 In Bone Tissue Regeneration
- •4.2 In Neural Regeneration
- •4.3 In Photodynamic and Photothermal Therapy
- •4.4 In Enhancing Cellular and Humoral Immunity
- •4.6 Miscellaneous
- •5. Challenges and Future Perspective
- •6. Conclusion
- •References
- •Carbon Quantum Dots Based Materials for Drug Delivery
- •1. Introduction
- •2. Synthesis Process of Carbon Quantum Dots
- •2.1 Top-Down Approaches
- •2.2 Bottom-Up Approaches
- •2.3 Microwave-Assisted Method
- •2.4 Electrochemical Method
- •2.5 Laser Ablation Method
- •2.6 Pyrolysis Method
- •2.7 Template-Assisted Method
- •4. Challenges and Future Perspective
- •5. Concluding Remarks
- •References
- •Carbon-based Nanocarriers for Sustained Drug Release in Dentistry
- •1. Introduction
- •2.1 Oral Mucosa Structure
- •2.2 Sites for Drug Delivery
- •2.3 Permeability
- •3. Local Drug Delivery for Dental Diseases
- •3.1 Odontogenic Infection
- •3.2 Non-odontogenic Infection
- •4. Bio-adhesive Nanoparticles: Novel Treatment Modality
- •4.1 Bio-adhesive Nanoparticles
- •4.2 Mechanism of Bioadhesion
- •5.1 Carbon Nanotubes
- •5.2 Graphene
- •5.3 Nanodiamonds
- •5.4 Fullerenes
- •5.5 Porous Carbon
- •5.6 Carbon Dots
- •6. Drug Delivery Systems Based on CBNs
- •6.2 Immediate Drug Delivery System (IDDS)
- •6.3 Sustained-release Drug Delivery Systems
- •6.4 Controlled Drug Delivery System (CDDs)
- •8. Conclusion
- •References
- •Fullerene Based Materials for Drug Delivery
- •1. Introduction
- •2. Types of Fullerene Derivatives
- •2.1 Exohedral Fullerene Derivatives
- •2.2 Endohedral Fullerene Derivatives
- •2.3 Surface Derivatized Fullerenes
- •3. Interaction of Fullerene Derivatives for Drug Delivery
- •4. Fullerene Based Materials for Drug Delivery
- •4.1 Nucleic Acid Delivery
- •4.2 Peptide Delivery
- •4.3 Topical Drug Delivery
- •4.4 Infectious Diseases Drug Delivery
- •4.5 Anticancer Drug Delivery
- •4.7 Brain Drug Delivery
- •4.8 Ocular Drug Delivery
- •5. Challenges and Future Perspectives
- •6. Concluding Remarks
- •6.1 Abbreviations
- •References
- •Graphene Quantum Dots-based Nanomaterials for Drug Delivery
- •1. Introduction
- •2. Synthesis of GQDs
- •3. GQD’s Properties for Drug Delivery
- •3.1 Optical Properties
- •3.2 Physicochemical Properties
- •3.3 Mechanical Properties
- •3.4 Biocompatibility and Cytotoxicity
- •4. Characterization of GQDs-Based Nanomaterials
- •4.1 Characterization of Multifunctional GQDs-Based Nanomaterials
- •5.1 Strategies for Developing Medication Delivery Systems Based on GQD
- •5.2 PH-responsive Drug Delivery Systems (GQD-DDSs)
- •5.3 Targeted Drug Delivery Using Ligand-Based GQDs as a Mediator
- •5.4 Improvement of Medicines’ Pharmacological Properties Using GQDs
- •5.5 Enhancing Cytotoxicity with GQD-DDS
- •7. Applications of Chiral GQDs
- •10. Challenges and Future Perspectives
- •11. Conclusions
- •References
- •Carbon Nano-onions for Drug Delivery
- •1. Introduction
- •2. Carbon Nano-Onion: A Multi-Layered Nanocarrier
- •3. Synthesis of Carbon Nano-Onions
- •3.1 Annealing Method
- •3.2 Carbon Ion Implantation Method
- •3.3 Arc Discharge Method
- •3.4 Carbon Vapour Deposition Method
- •3.5 Pyrolysis Method
- •6. Carbon Nano-Onions in Drug Delivery
- •6.1 Delivery of Therapeutic Agents
- •6.2 Delivery of Targeting Agents
- •6.3 Delivery of Imaging Agents
- •7. Challenges and Future Perspectives
- •8. Concluding Remarks
- •References
- •Chitosan/Carbon Nanocomposites in Drug Delivery and Cardiovascular Diseases
- •1. Introduction
- •1.1 Drug Delivery
- •1.2 Cardiovascular Diseases
- •1.3 Chitosan and Its Properties
- •1.4 Chitosan/Carbon Nanocomposites
- •2. Chitosan/Carbon Nanocomposites in Drug Delivery
- •3. Chitosan/Carbon Nanocomposites in CVDs
- •3.1 Chitosan-Based Scaffolds
- •3.2 Chitosan in Cardiac Tissue Engineering
- •3.3 Chitosan-Based Cell Therapy
- •3.4 Chitosan-Based Gene Delivery
- •3.5 Chitosan-Protein Interaction
- •4. Challenges and Future Perspective
- •5. Concluding Remarks
- •References
- •Graphene Reinforced Chitosan Nanocomposites for Drug Delivery
- •1. Introduction
- •2. Chitosan: Structure and Properties
- •3. Graphene: Structure, Types and Properties
- •4.1 Electrospinning Method
- •4.2 Sol–gel Method
- •4.3 Solution Mixing Method
- •4.4 In-situ Polymerization Method
- •5.2 Chitosan/Graphene Aerogels
- •5.3 Chitosan/Graphene Hydrogels
- •5.4 Chitosan/Graphene Thin Films
- •6.1 Oral Drug Delivery
- •6.2 Mucosal Drug Delivery
- •6.3 Transdermal Drug Delivery
- •6.4 Parenteral Drug Delivery
- •7. Challenges and Future Perspectives
- •8. Concluding Remarks
- •References
- •1. Introduction
- •2. Functionalization of CNFs
- •2.1 The Need for Functionalization

Carbon Quantum Dots Based Materials for Drug Delivery 265
2.5 Laser Ablation Method
This is a top-down approach that uses a high-energy laser beam to vaporize a carbon
target. This method enables precise control over the size and surface chemistry of
CQDs [18]. In this technique, a carbon target is irradiated with a high-energy laser
beam in the presence of a suitable solvent. The intense laser energy causes the carbon
target to vaporize, generating CQDs that are subsequently dispersed in the solvent.
This method enables precise control over the size and surface chemistry of CQDs
[19].
2.6 Pyrolysis Method
It is s a top-down approach that involves the heat-induced decomposition of carbonrich precursors. This method offers good control over the synthesis parameters and
can produce CQDs in large quantities [20]. In the pyrolysis technique, carbon-rich
precursors, such as organic compounds or polymers, undergo high-temperature treatment within an inert atmosphere. The heat-induced decomposition of precursors
leads to the formation of CQDs. This method offers good control over the synthesis
parameters and can produce CQDs in large quantities [21].
2.7 Template-Assisted Method
This is a bottom-up approach that uses a pre-formed template or matrix to control
the size and shape of the produced CQDs. This method allows for the production
of CQDs with well-defined structures [22]. In this approach, carbon precursors are
introduced into a pre-formed template or matrix, such as silica or polymer templates.
The carbonization and subsequent removal of the template result in the formation
of CQDs with controlled sizes and shapes. This method allows for the production
of CQDs with well-defined structures [23]. These are just a few examples of the
synthesis methods used for the production of CQDs [24–26]. As represented in
Table 1, each method has its advantages and limitations, and the choice of synthesis
method depends on the desired properties, scalability, and application requirements
of the CQDs. Researchers continue to explore and develop new synthesis techniques
to further enhance the synthesis efficiency and to hold control over the properties
of CQDs. Figure 1 displays various carbon dots, including graphene quantum dots,
carbon nanodots, and polymer dots, alongside different ‘top-down’ and ‘bottom-up’
synthesis methods.

Tabl e 1 Advantages and Limitations of CQDs’ Synthesis Methods
Method Advantages Limitations References
Hydrothermal/
Solvothermal Method
Microwave Assisted
Method
Controlled Size and Luminescence:The
hydrothermal/solvothermal method allows for precise
control over the size and luminescence properties of
CQDs, resulting in uniform particles with desirable
characteristics
Environmentally Friendly: This technique is carried
out in water-based solutions, making it
environmentally friendly and compatible with
biological systems
Scalability: Hydrothermal/solvothermal synthesis
can be easily scaled up for mass production without
compromising product quality
Enhanced Stability: CQDs obtained through this
method often exhibit improved chemical and thermal
stability
Rapid Synthesis: Microwave-assisted synthesis
significantly reduces reaction times, allowing for
faster production of CQDs compared to conventional
methods
Uniformity: This technique can lead to the formation
of well-dispersed and uniform CQDs with controlled
size and properties
Energy Efficiency: Microwave heating is an
energy-efficient approach that reduces overall energy
consumption during the synthesis process
Time-consuming: The hydrothermal/solvothermal process can be time-consuming,
especially for the growth of larger-sized CQDs
Complex Reactor Setup: The reaction requires a high-pressure, temperature-controlled
reactor, which may add to the overall synthesis cost
Limited Surface Functionalities: The hydrothermal/solvothermal method may offer fewer
options for introducing specific surface functional groups compared to other techniques
Potential Overheating: If not carefully controlled, microwave synthesis can lead to localized
overheating, resulting in the formation of undesired by-products or reduced product quality
Limited Scale-up: While microwave-assisted synthesis is efficient on a laboratory scale,
challenges may arise when attempting to scale up production
[27]
[28]
(continued)
266 M. Pourmadadi et al.

Tabl e 1 (continued)
Method Advantages Limitations References
Electro-chemical
Method
Laser Ablation Method Size and Morphology Control: The laser ablation
Environmental Friendliness: Electrochemical
synthesis is a green method that minimizes the use of
hazardous chemicals and reduces waste generation
Precise Control: This technique allows for precise
control over the size, surface functional groups, and
optical properties of CQDs
Scalability: Electrochemical synthesis can be easily
scaled up for mass production without sacrificing
product quality
In Situ Synthesis: CQDs can be synthesized directly
in the desired application medium, enabling seamless
integration into devices or systems
method allows for precise control over the size and
morphology of CQDs by adjusting laser parameters
Minimal Chemical Contamination: This technique
does not require chemical reagents, reducing the risk
of contamination and making it suitable for
biomedical applications
High Purity: Laser ablation typically yields highly
pure CQDs without the presence of unwanted
impurities
Electrode Material Selection: The choice of electrode material can significantly influence
the properties of the resulting C QDs, requiring careful consideration
Electrolyte Sensitivity: The properties of the CQDs may be affected by the composition and
pH of the electrolyte, necessitating optimization for specific applications
Complex Electrochemical Setup: The setup for electrochemical synthesis can be more
complex and may require specialized equipment
Lower Yield: Compared to other methods, the yield of CQDs through electrochemical
synthesis can be relatively lower
Limited Scalability: Laser ablation is more suitable for laboratory-scale production and may
not be easily scalable for mass production
Complex Setup: The laser ablation setup involves sophisticated equipment and careful
control of laser parameters, which can be challenging and expensive
Lower Yield: The yield of CQDs obtained through laser ablation may be lower compared to
some other synthesis methods
[29]
[30]
(continued)
Carbon Quantum Dots Based Materials for Drug Delivery 267

Tabl e 1 (continued)
Method Advantages Limitations References
Pyrolysis Method High Yield: The pyrolysis method often yields a
Template-Assisted
Method
high quantity of CQDs, making it suitable for
large-scale production
Simple and Cost-effective: This technique is
relatively straightforward and cost-effective, as it
involves the thermal decomposition of readily
available organic precursors
Water Solubility: The resulting CQDs from
pyrolysis can exhibit excellent water solubility,
which is advantageous for applications in
biomedicine and biological imaging
Versatility: The method allows for the incorporation
of different precursor materials, enabling the tuning
of CQD properties
Controlled Size and Shape: Template-assisted
synthesis allows for precise control over the size,
shape, and distribution of CQDs by using templates
or molds
Versatility: Different types of templates can be
employed, enabling the synthesis of CQDs with
diverse properties for various applications
Reproducibility: This method often offers good
reproducibility, ensuring consistent CQD
characteristics in multiple synthesis runs
Limited Control over Size and Properties: Pyrolysis can produce a range of CQD sizes, but
achieving precise control over size and other properties can be challenging
Less Control over Surface Functionalities: The functional groups on the surface of the
CQDs may not be easily controllable using this method
High Temperature Requirement: The high temperatures involved in pyrolysis may cause
undesirable side reactions and reduce the selectivity of CQD formation
Template Removal: The process of removing the template after CQD synthesis can be
challenging, and residual template materials may impact the properties of the final product
Additional Steps: Template-assisted synthesis may involve additional steps compared to
other methods, potentially increasing complexity and cost
Limited Scalability: The scalability of this method may be limited, especially when dealing
with intricate templates or large-scale production
Each synthesis method for CQDs presents its unique advantages and limitations, and
researchers choose the most suitable technique based on the intended application, desired
properties of the CQDs, and available resources. As CQD research progresses, innovations in
synthesis methodologies continue to drive the field forward, unlocking new possibilities and
applications for these versatile nanomaterials
[31]
[32]
268 M. Pourmadadi et al.

Carbon Quantum Dots Based Materials for Drug Delivery 269
Fig. 1 a Carbon dots including graphene quantum dots, carbon nanodots and polymer dots. Reproduced with permission from American Chemical Society [24] b Carbon dots synthesized from “topdown” and “bottom-up” approaches. Reproduced with permission from Royal Society of Chemistry
[25]
3 Carbon Quantum Dots-Based Materials for Drug
Delivery
3.1 Carbon Quantum Dot/Polymer-Based Materials for Drug
Delivery
CQDs are carbon-based materials with a size distribution range of 4–10 nm. This
material has some characteristic features such as photoluminescence properties, high
physicochemical stability, chemically inert features, and acceptable biocompatibility
[11]. CQDs have been mostly employed and modified by polymeric structures to
enhance their characteristic features. For instance, the surface functionalization can
make active sites on CQDs by the help of -OH, -NH-, and -SH functional groups,
which would ameliorate the solubility in aqueous media, resulting in bioavailability
improvement. Moreover, these modifications introduce CQDs in a polymeric matrix
for efficient drug delivery applications with an increased drug half-life and permeable nanoscale drug delivery with high affinity to tumors. Furthermore, thanks to
CQDs’ fluorescence and photoluminescence properties, the drug delivery process
including loading, targeting, and release can be detected, indicating a great potential
for theragnostic purposes [33, 34].
Feng et al. [35], employed the photoluminescence feature of CQDs as a detectable
nanocarrier modified by polyethylene glycol, RGD, and Pt (IV) for delivering
cisplatin in a targeted manner. They obtained a pH-sensitive drug release behavior in
the tumor microenvironment. Moreover, their results revealed that cisplatin (IV) has
turned into cisplatin (II) after cellular uptake during the reduction process within the
cytoplasm, indicating an effective targeted anticancer activity. In another study, Gong
et al. [36], employed phosphorus and nitrogen-doped CQDs to carry doxorubicin
(DOX) and to release drug in a pH-sensitive environment. Their release outcomes

270 M. Pourmadadi et al.
demonstrated an enhanced drug release and fast DOX uptake by the cancer cells.
Furthermore, Shu et al. [37] employed organophilic CQDs as a nanocarrier for
curcumin (CUR) with a high loading capacity. They showed that chemotherapy efficacy was enhanced due to the increased permeability of CUR-loaded organophilic
CQDs. Besides, Yang et al. [38] developed polyamine including organosilane structures made CQDs less active to carry DOX as an active agent for targeted delivery
and theragnostic applications to treat breast cancer cells (MCF-7). Their results
indicated low cytotoxicity toward healthy tissues and improved MCF-7 apoptotic
effects under exposure to DOX-loaded CQDs with above 62% loading capacity.
Sung et al. [39] developed a photo-sensitive nanocarrier for encapsulating docetaxel
into the sponge-like carbon dot structures modified by red blood cells as the outer
membrane. Their results showed an enhanced apoptotic effect against targeted tumors
under the NIR irradiation and during the 3-week treatment process. In some studies,
CQDs have been functionalized by folic acid (FA) as a ubiquitous ligand for targeted
cancer therapy with a high affinity toward repeatedly expressed folate receptors on
diverse tumor cells. In this regard, Li et al. [40], employed functionalized and Ndoped CQDs with FA as the alternative chemotherapy procedures to treat cancers.
They obtained the visualized cancer therapy through above 93% cellular uptake and
within the 30-day survival period during phthalocyanine with FA as the targeting
ligand for targeted cancer therapy. Their results showed an enhanced apoptotic
effect against HeLa cell lines. Furthermore, Zhang et al. [41] fabricated the functionalized FeN@CQDs nanocomposites with riboflavin and FA for assisted photoresponsive delivery of DOX in a targeted manner synergistically with photothermalthermodynamic combination therapy procedures to optimize the cancer treatment
efficacy. Their results indicated an enhanced DOX delivery under the NIR irradiation as the external stimulus. In the provided Fig. 2a, the fabrication process of
the polymeric-based nanomaterials composed of CDs have been depicted, which
have been fabricated through diverse natural and synthetic procedures with required
physicochemical modifications. Furthermore, the application of these materials is
summarized in the Fig. 2b.
3.2 Carbon Quantum Dot/Polysaccharide-Based Materials
for Drug Delivery
Polysaccharides are central molecules consisting of monosaccharide units allied with
each other via glycosidic linkages. These complex structures can be break down
into smaller units, including oligosaccharides or monosaccharides, by hydrolysis.
Consequently, they have been widely utilized as a carbon source for synthesizing
CQDs, serving as a raw material not only due to the abundance of carbon molecules
but also owing to their accessibility, high water solubility, and low carbonization temperatures. Furthermore, due to the presence of heteroatoms, including N
and S, in polysaccharides, they are widely employed to prepare naturally doped

Carbon Quantum Dots Based Materials for Drug Delivery 271
Fig. 2 a, b Fabrication process of CQDs-based polymeric nanocomposites and their applications
in biomedical applications. Reproduced with permission from MDPI [ 42, 43]
CQDs. Furthermore, marine polysaccharides have emerged as excellent precursors for sulfur- and nitrogen-containing carbon-based nanomaterials. For instance,
carrageenan is composed of linear chains of galactose molecules that are alternately
sulfated and non-sulfated. Furthermore, it contains hydroxyl groups which can significantly impact water solubility and quantum yield of CQDs [42, 44]. Emam et al.
employed carrageenan to synthesize carrageenan-based CQDs and monitor functional groups’ effect on breast cancer cells and viral cells in the C-dots. The results
suggest that the C-dots could be considered a source for antitumor reagents in cancer
chemotherapy [45].
Another major polysaccharide is chitosan which possesses a high amount of
nitrogen (7wt.%) [46] and various functional groups such as acetamido, hydroxyl, and
amino groups [47]. This defining characteristic of chitosan can be exploitedas a single
carbon and nitrogen precursor to obtain N-doped carbon nanomaterials [48–52]. For
instance, Mathew et al. synthesized chitosan-based C-dots by carbonization, conjugating them with chitosan to achieve a chitosan/carbon dot matrix. Subsequently, the
matrix is laden with dopamine, widely employed as an administrated treatment for
neurodegenerative diseases such as Parkinson’s disease (PD) or Alzheimer’s disease
(AD). As a result, nanocomposites with the size of 144 nm and 60% cumulative
release at pH 4 were obtained, proving the pH-dependence drug release [53]. In
another study, chitosan and silk-fibronin were employed as the carbon and nitrogen
sources to achieve N-dopped CQDs with high fluorescent intensityand quantum

272 M. Pourmadadi et al.
yield. Afterward, the nanoparticles are conjugated with biotin and loaded with
5-fluorouracil (5-FU) as an anti-cancer drug to act as a functional cell-targeted
nano-theranostic tool. Comparing the localization of CQDs with biotin-CQDs, it
is suggested that the biotin-CQDs are distributed in the whole cell, chiefly in the
nucleus, highlighting suitable cell-targeting properties [54]. In another study, Gogoi
et al. synthesized calcium alginate beads coated with chitosan-based CQDs. The
synthesized biomaterial revealed appropriate stability over two months in atmospheric conditions. In this system, carboxylate residues of alginate and protonated
amino residues of chitosan ironically interact with each other and form a polyelectrolyte complex. Moreover, they employed Tetracycline, an antibiotic exhibiting antiinflammatory action and effective against imbalance diseases, and β-cyclodextrin as
a complexing agent for evaluation of drug release behavior of nanocarriers. The
results show more than 90% drug loading and 61% drug release at pH 1 [55].
Alginate is a linear biopolymer and is a highly abundant polysaccharide containing
carboxyl and hydroxyl groups which widely used for drug/gene delivery systems to
fulfill selective cell targeting [56, 57]. However, it is rarely employed as a carbon
precursor t o synthesize CQDs. Furthermore, alginate can turn natural polysaccharides into multifunctional biomaterials for bioimaging and targeted drug delivery.
In this regard, in a study, pH-responsive fluoresce C-dots were fabricated by onestep microwave irradiation. The alginate was selected as the core source, and urea
was the surface-decorating N-doping ligand. Furthermore, due to the many functional groups on the C-dots’ surface, covalent conjugation with drugs was enhanced;
therefore, DOX was employed to attach to the nanocarrier as a drug model by the
EDC-NHS approach. The fluorescent C-dots revealed a quantum yield of around
48% and a controlled drug release in physiological pH [58].
Sheng et al. examine the synthesis and characterization of Graphene Quantum
Dots (GQDs) derived through the pyrolysis of citric acid. These GQDs were utilized
for loading hydrophilic cytarabine (Cyt), an anti-cancer drug. Chitosan (CS) gels
were employed to encapsulate the Cyt-loaded GQDs (Fig. 3). The presence of CS
significantly improved the fluorescent stability of GQDs, presumably due to the
inhibition of GQD agglomeration by CS gels. Furthermore, the CS coating effectively
reduced the burst release of Cyt from the carrier. Cyt was introduced into GQDs via
an amidation reaction, resulting in pH-sensitive drug delivery attributed to the amido
linkage hydrolysis between GQDs and Cyt in acidic environments.
3.3 Carbon Quantum Dot/ Metal-Based Materials for Drug
Delivery
As well as many kinds of heteroatoms (nitrogen, phosphorus, sulfur, etc.), several
metals such as Zn, W, Fe, Ag, and Mg are employed as doping agents to strengthen
the C-dots properties [60–62]. In addition, several of these atoms including Fe,
Cu, Mg, Co, Ca, etc., can be found in the body. When compared to commonly

Carbon Quantum Dots Based Materials for Drug Delivery 273
Fig. 3 Schematic illustration of preparation of CS/GQDs/Cyt. Reproduced with permission from
Elsevier [59]
employed heteroatoms like nitrogen, sulfur, fluorine, etc., the referenced metals
exhibit superior electron-donating capabilities, possess more unoccupied orbitals
in their vicinity, and boast larger atomic radii. Consequently, the incorporation of
these doping agents into C-dots facilitates a more straightforward modification of
charge density or charge transition between the C-dot matrix and metal ions, thereby
enhancing the physical properties of C-dots [61]. Metal doping agents are highly
beneficial to C-dots, including increased optical absorbance because of the charge
transition from metal ions to C-dots, enhancement of the quantum yield, revelation
of multiple color emissions, and improved antimicrobial activities. Additionally,
the conjugation of metal oxide nanoparticles, such as Cu
,Fe2C5, etc., with C-dots leads to an increased production rate of light-induced
Fe
3O4
O, MnO2,WO3,Fe2O3,
2
reactive oxygen species (ROS) in C-dots. This enhancement is attributed to the
outstanding upconversion photoluminescence behavior, exceptional photo-induced
electron transfer, and distinctive possession of electron reservoirs by C-Dots [60, 63,
64]. Wang et al. synthesized a multifunctional hybrid nanomaterial integrated with
the magnetic Fe
nanocrystals, CQDs, and Au nanoparticles in a porous carbon
3O4
matrix which can be employed for magnetic/NIR-responsive drug release or optimized photothermal therapy. The DOX was loaded in the nanocarrier with a loading
capacity of 71.9%, which by an alternation of a magnetic field; the drug will be triggered and released. The Au nanocrystals not only optimize the photothermal property
of drug carrier but also enhance the efficiency of killing tumor cells in the presence of
NIR irradiation [65]. In another study, a nanohybrid biomaterial consists of fluorescent carbon dots and magnetic iron oxide nanocrystals, which surface modified by
polyglycerol grafting were synthesized. Furthermore, a platinum-based anticancer
drug is loaded on the nanocarrier’s surface to enhance magnetically drug delivery. The
in vivo studies using HeLa subcutaneous xenografts revealed an improved efficacy of
cancer therapy [66]. In another study, magnetic Fe
nanocrystals were employed
3O4
to supplement C-dots in porous carbon. The synthesized biomaterial exhibits high

274 M. Pourmadadi et al.
loading capacity for DOX and chiefly can alter NIR light to heat in favor of Cdots; therefore, it can be utilized as a NIR-controlled drug release and photothermal/
chemotherapy [67].
Pandey et al. synthesized gold-dopped CQDs from gold nanorod and gum Arabic
by microwave-assisted method for drug delivery, photothermal therapy, or biological imaging. The resulting C-dots@GNR complex was loaded with DOX and
showed high drug loading capacity mainly because of C-dots’ porous nature. The
conjugation displayed an increased cytotoxic effect on MCF-7 cells which was
enhanced in the presence of NIR laser irradiation (due to the conjunction of the
photothermal property of GNRs, and laser-induced gentle drug release) [68]. In
another study hydrothermal treatment synthesized iron- and nitrogen-doped CQDs
from chitosan and FeCl
.6H2O. Subsequently, the nanocarrier was conjugated with
3
FA and riboflavin to prepare a NIR-triggered and targeted synergistic chemophototherapy agent. Finally, the DOX was encapsulated in the nanocarrier through
physicochemical interactions to enable a targeted drug delivery system. To evaluate
the responsiveness of the nanocarrier to pH and NIR light, the drug was released about
60% at pH 7, whereas only 22% was released at physiological pH. Furthermore, the
profile release of the drug in the presence of NIR light showed an enhancement
that can result from increased temperature because of the photothermal property
of the nanoparticles. The results from the injection of the carrier in tumor-bearing
mice with simultaneous laser irradiation proposed a completely eradicated tumor at
21 days [41].
In a recent investigation, Chung et al. achieved the successful synthesis of iron
oxide nanoparticles coated with a chitosan-PEG copolymer and carbon dots (CNPCP)
through a coprecipitation method. The primary objective of this study was to assess
the solubility and stability characteristics of the resulting CNPCP in aqueous environments. The chitosan-PEG coating was found to provide initial solubility, while
the steric stability imparted by the PEG prevented aggregation and ensured the welldispersion of CNPCP. The evaluation of the synthesized material proposed that it
can be employed as a fluorescent probe in cancer cell lines with little toxicity and
could enhance quantitative imaging. Moreover, DOX as a drug model was conjugated onto the CQDs to assess the ability of killing cancer cells in a dose dependent
manner. The synthesis mechanism of CNPCP is illustrated in Fig. 4a, where the
chitosan-PEG coating facilitated the formation of carbon dots (CD) on the surface of
the nanoparticles. The resulting solution exhibited a dark brown color and displayed
high fluorescence, as shown in Fig. 4b. This fluorescence property suggests potential applications not only in drug delivery systems but also in various fields such as
bioimaging and sensing [69, 70].
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