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Carbon Nano-onions for Drug Delivery 405
exploited as drug delivery targets (Fig. 13.6). The idea behind this is that the nano­onion’s layers can be created to have particular chemical characteristics, with such affinity for a particular kind of cell or tissue. The medicine can be given precisely to the target cells or tissue by being encapsulated within the nano-onion. Increased medication bioavailability, less toxicity to organs other than the target, and enhanced pharmacokinetics are benefits of utilizing nano-onions as targeting agents. However, there may be certain disadvantages, such as the difficulty in producing and char­acterizing the nanoparticles and the possibility of immunogenicity. A noteworthy example is the development of hyaluronic acid-conjugated carbon nanomaterials for improved tumor targeting ability [58, 59]. Targeting tumor cells that overexpress the CD44 + receptor with chemo and photo thermal therapy uses hyaluronic acid. Carbon nanomaterial (CNM) carriers can effectively carry anticancer medications, such as doxorubicin and gemcitabine, to the tumor locations, thanks to HA-targeting hybrid systems. Using hyaluronic acid, carbon nano-onions have shown to be quite promising for the delivery of specific drugs [60]. A HA-phospholipid compound was used in the work by d’Amor et al. to target cancer cells that overexpress CD44 while improving the solubility of the nanostructure. In comparison to human ovariancancer cells with undetectable levels of CD44, non-covalently functionalized carbon nano­onions with HA-phospholipids conjugate exhibit outstanding in vitro cell survival in human breast carcinoma cells [61]. Additionally, they have a high level of in vivo biocompatibility in zebrafish (Daniorerio) at various developmental stages and are mostly found in the digestive system of zebrafish larvae. Mamidi et al. discovered that the nano-onions complex with other nanoparticles might thrive as a viable pH and temperature-triggered drug delivery platform for GI tract and colon focused drug delivery [62]. There are various instances of nanocarrier systems on the market that have received FDA approval, demonstrating the effectiveness of the nanocarrier method in this regard. This viewpoint confirms that carbon nano-onions have the potential to serve as nanocarriers for the delivery of drugs. Already described are the many standards and factors to take into account when constructing a nanocarrier [18].

6.3 Delivery of Imaging Agents

A chemical called an imaging agent is used to improve the image quality in medical imaging procedures like computed tomography and magnetic resonance imaging, among others. The potential for using nano-onions, which are microscopic particles comprised of concentric layers of carbon, as imaging agents has been investigated. The idea behind employing nano-onions as imaging agents is that they are capable of being functionalized with targeting molecules like antibodies or peptides, which can then bind specifically to sick cells or tissues [63]. This makes it possible to image the targeted area of interest with greater accuracy and precision. Encapsulating the imaging agent within the onion-like structure’s layers at the nanoscale level, which can then be coated with a biocompatible substance to prevent degradation and boost
406 S. Yasri and V. Wiwanitkit
Fig. 13.6 Ta rge t ing an d imaging conjugate of nano-onion
stability,is the first step in the delivery of imaging agents utilizing nano-onions. Nano­onions are advantageous as imaging agents due to their small size, which enables them to reach deep within tissues and organs, biocompatibility, and potential for multi functionalization. Cons include possible toxicity and difficulties with production scaling up and manufacturing. However, work is still being done to overcome these obstacles and boost the efficiency of nano-onions as imaging agents. At present, there are some reports on the application of nano-onions on this specific purpose. The good examples are the reports on application for imaging several cancers [64, 65]. The applications of fluorescent nano-onions are the new hope in clinical medicine for management of several disorders (Fig. 13.7).
There are several fascinating reports on the use of nano-onions for imaging agent delivery. First, Bowman et al. reported that onion-like carbon is used in engineered three-dimensional breast tumor models composed of phantom tissue mimicking infil­trating ductal carcinoma surrounded by phantom tissue mimicking healthy fibro glandular tissue due to its strong interaction with terahertz frequencies and ability to be activated for selective binding to cancer cells. Bowman et al. reported that this model is scanned utilizing the terahertz reflection mode to test the efficiency of contrast agents for tissue differentiation. A 10% concentration of onion-like carbon has the greatest impact on the terahertz signal in both spectroscopy and imaging and offers promise as a terahertz contrast agent [64]. Another study by Bartelmess et al. [65], was found that the addition of a terminal bromo substituent allows the fluo­rophore to be immobilized on the surface of carbon nano-onions, resulting in potential
Carbon Nano-onions for Drug Delivery 407
Fig. 13.7 Clinical applications of fluorescent nano-onion in clinical medicine
imaging agents for biological and biomedical applications. Sun et al. created water­dispersible carbon nano-onion clusters with an average hydrodynamic size of 90 nm by simply sonicating candle soot in an oxidizing acid combination. They discovered that following intravenous delivery, the complex can be employed for photothermal/ photoacoustic dual-modal imaging-guided photothermal therapy. Furthermore, the complex may be eliminated from the mouse body in less than a week, providing its long-term biosafety [66].

7 Challenges and Future Perspectives

Due to their distinct physicochemical characteristics, high surface area, biocompati­bility,and low t oxicity, carbon nano-onions have become a potential material for drug delivery. However, there are still some issues and considerations for the future that must be addressed. The production of carbon nano-onions with controlled s ize, shape, and functionalization is one of the key difficulties. The majority of current synthesis techniques rely on thermally processing carbon precursors, which can produce a variety of forms and sizes. Additionally, functionalizing carbon nano-onions with medicinal compounds or targeted ligands is still a challenging task that has to be developed further. Understanding how carbon nano-onions interact with biological systems is another difficult task. Although carbon nano-onions are regarded biocom­patible, their in vivo behavior is still unknown. Furthermore, the mechanisms of cellular absorption and intracellular trafficking of carbon nano-ions must be under­stood. Carbon nano-onions have the potential to transform medication delivery by
408 S. Yasri and V. Wiwanitkit
enabling focused therapy, controlled release, and imaging in the future. Further­more, their distinct features could be used in other biological applications like as tissue engineering and biosensing. Finally, carbon nano-onions have demonstrated remarkable potential as a medium for future drug delivery.

8 Concluding Remarks

To summarize, carbon nano-onions are a potential and novel strategy to drug delivery, with their unique structure and physicochemical features allowing for enhanced drug targeting and release. These nanoparticles’ prospective applications in several disciplines of medicine, including cancer therapy, are particularly fascinating. More research is needed, however, to completely understand the biological interactions and toxicity of carbon nano-onions, as well as to improve their designs for specific drug delivery applications. Overall, the invention of carbon nano-onions for drug delivery is a significant step toward more effective and tailored treatments for a variety of ailments.
Conflict of Interest Authors declare no conflict of interest.

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Chitosan/Carbon Nanocomposites in Drug Delivery and Cardiovascular Diseases

Ayman M. Mahmoud, Ahmed M. Sayed, Emad H. M. Hassanein, Krishna Manjari Sahu, and Sarat Kumar Swain
Abstract Controlled and sustainable delivery of therapeutics for accurate adminis-
tration at requisite location with proper number of dosages are essential to treat diverse fatal diseases by reducing patient complications and improving safety concerns related to drug administration. Cardiovascular diseases (CVDs) are a class of serious disorders that represent the leading cause of mortality worldwide. Chitosan (CS) is a natural and biocompatible polysaccharide that shows promising properties in various fields, namely, drug, gene, and therapeutic proteins delivery, and the fabri­cation of scaffolds and hydrogels for tissue engineering. It exhibits structural similar­ities with glycosaminoglycans which represent the main component of the extracel­lular matrix (ECM), and hence possesses great potential for tissue engineering and other therapeutic purposes. CS possesses fascinating mechanical properties but poor electrical properties, therefore several modifications have been performed to enhance the electrical properties of CS-based scaffolds. To modify the characteristic features of CS, carbonaceous nanomaterials like carbon nanotube (CNT), graphene, carbon dot, carbon nanohorn (CNH), carbon nano-onion (CNO) and nanodiamond (ND) are effectively implemented. This chapter introduces the recent findings, latest develop­ments, and innovations in the use of CS/carbon nanocomposite in drug delivery and treatment of CVDs. The beneficial effects of CS/carbon nanocomposite in cardiac tissue engineering, cell therapy, gene delivery, and its interaction with proteins are also discussed in this chapter.
A. M. Mahmoud (B) Department of Life Sciences, Faculty of Science and Engineering, Manchester Metropolitan University, Manchester, UK e-mail: a.mahmoud@mmu.ac.uk
A. M. Sayed Biochemistry Laboratory, Chemistry Department, Faculty of Science, Assiut University, Assiut, Egypt
E. H. M. Hassanein Department of Pharmacology and Toxicology, Faculty of Pharmacy, Al-Azhar University, Assiut, Egypt
K. M. Sahu · S. K. Swain ( Veer Surendra Sai University of Technology, Burla, Sambalpur, India e-mail: skswain_chem@vssut.ac.in
B
)
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414 A. M. Mahmoud et al.
Keywords Carbonaceous nanomaterials · Chitosan · Cardiovascular diseases · Cardiac tissue engineering · Drug delivery
Abbreviations
1
H NMR Proton nuclear magnetic resonance 5-FU 5-Fluorouracil AFM Atomic force microscopy AGO Amine functionalized Graphene oxide Apt Aptamer ATR-IR Attenuated total reflectance- infrared Spectroscopy C
60
CMC Carboxymethyl cellulose CMCS Chemically modified chitosan CS Chitosan DCA-HPCHS Mphiphilic deoxycholic acid modified-hydropropyl chitosan DOX Doxorubicin FA Folic acid FA-COS Folic acid–chitosan oligosaccharide conjugate FTIR Fourier transform infrared Spectroscopy GC
1
HA
1
HPLC High-performance liquid chromatography MOFs Metal organic framework ND-OH Hydroxylated nanodiamond OCMC O-carboxymethyl chitosan SEM Scanning electron microscope SWNH Single-walled carbon nanohorns TEM Transmission electron microscope TTP Tripolyphosphate UPLC Ultra performance liquid chromatography UV-Vis UV–vis spectrophotometer XRD X-ray diffractometer
C60fullerene
Galactosylated chitosan Hydroxyapatite