Добавил:
kiopkiopkiop18@yandex.ru t.me/Prokururor I Вовсе не секретарь, но почту проверяю Опубликованный материал нарушает ваши авторские права? Сообщите нам.
Вуз: Предмет: Файл:
Ординатура / Хирургия / Библиотека им академика М.И. Перельмана / Книга_5882_Библиотеки_им_академика_М_И_Перельмана.pdf
Скачиваний:
0
Добавлен:
31.08.2026
Размер:
22 Мб
Скачать
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 [2426]. 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 [4852]. 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 [6062]. 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].
Соседние файлы в папке Библиотека им академика М.И. Перельмана