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Carbon Nanomaterial-Incorporated Supramolecular Drug Delivery 165
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Carbon Nanomaterial-Based Polymeric Nanocomposites for Drug Delivery

Danyang Song and Hongbin Li
Abstract As the research on drug delivery systems continues to improve, the use of
carbon nanomaterials in drug delivery is becoming more and more widespread, but there are limitations to the use of carbon nanomaterials alone in drug systems, so the use of nano-polymers in combination with carbon nanomaterials is more conducive to the use of drug delivery, which in the area of drug delivery is mainly used in the field of anticancer therapy, topical therapies, and the treatment of infectious diseases, and so on.
·
Keywords Carbon nanomaterials delivery
Lung-specific drug delivery·Oral drug delivery
·
Abbreviations
Polymer nanocomposite·Anticancer drug
CF Carbon fiber CNT Carbon nanotube CQDs Carbon quantum dots Cur Curcumin DOX Doxorubicin FA Folic acid FCNPs Fluorescent carbon nanoparticles FGQC Quantum dot/chitosan nanocomposites GLUT5 Glucose transporter protein GOM Graphene oxide monomer IONP Iron oxide nanoparticles
D. Song · H. Li (B) College of Light Industry and Textile, Qiqihar University, Qiqihar 161000, Heilongjiang, P. R. China e-mail: lhb987258@163.com
H. Li Engineering Research Center for Hemp and Product in Cold Region of Ministry of Education, Qiqihar University, Qiqihar, P. R. China
169
170 D. Song and H. Li
MIP Molecularly imprinted polymer MOFs Metal-organic framework MTX Methotrexate PB Probucol PVDF Polyvinylidene fluoride UCNPs Upconverted nanophosphorites VEGF Vascular endothelial growth factor ZIF-8 Zeolite imidazolate framework-8

1 Introduction

With the continuous progress of science and technology, single function and compo­sition of the material has long been unable to meet the growing demand. So, nanoscale polymer materials were created. Polymer nanomaterials are used in many applica­tions, including building materials [1], batteries [2, 3], glass [4, 5], sensors [6, 7], etc. This chapter focuses on their use in medicine. At present, there are hundreds of polymer nanocomposites that have been developed. Polymer nanocomposite is a kind of nanocomposite, in which when nanomaterial is the dispersed phase and the organic polymer is continuous phase. Polymer nanocomposite is a new type of mate­rial formed by various nano-units and organic polymer materials in various ways, in which the nano-units can be metal, inorganic, polymer, and many more.
Carbon-based materials mainly refer to the shielding materials made of carbon fiber (CF), silicon carbide fiber, carbon black, carbon nanotube (CNT), graphene, and other carbon materials as filling materials. Carbon-based materials take the aromatic ring structure formed by carbon atoms as their main structural frame­work, which has the characteristics of large specific surface area, uniform surface morphology, and developed pore structure. Depending on the dimensions, carbon­based materials can be categorized into four different materials from zero to three dimensions. Among them, zero-dimensional materials involve carbon quantum dots (CQDs) and fullerenes, one-dimensional materials encompass carbon fibers and CNTs, two-dimensional materials include graphene, three-dimensional materials are also called bulk materials, comprise of all kinds of three-dimensional intrinsic or composite systems. In a broad sense, carbon-based materials can be regarded as a material system with carbon atoms as the skeleton, including pure carbon systems like diamond and graphite and polyatomic systems such as silicon carbide and polymer organic compounds. Various carbon nanomaterials are illustrated in Fig. 1.
Carbon Nanomaterial-Based Polymeric Nanocomposites for Drug … 171
Fig. 1 Carbon nanomaterials
2 Drug Delivery Systems Using Carbon
Nanomaterial-Based Polymer Nanocomposites
By combining different carbon nanomaterials and polymers, various nanocompos­ites are utilized in drug delivery system. Carbon nanomaterials mainly introduce CQDs, CNT, graphene quantum dots, metal–organic framework, fullerenes, and nanodiamonds. Next, different drug delivery systems will be introduced according to the classification of carbon nanomaterials. Nano-carbon fillers such as graphene, graphene oxide, CNT, and metal-based nanoparticles play a pivotal role in the structure morphology and properties of carbohydrate polymer nanocomposites. The biocompatibility of polymers incorporating nanoparticles has advanced in numerous applications such as biosensors, antimicrobials, damage curing, and drug transport.

2.1 Carbon Quantum Dot-Based Polymer Nanocomposite

CQDs were first discovered in 2004 during the washing process of single-walled CNT [8]. CQDs are emerging categories of carbon-based nanomaterials with many unique properties and advantages. Due to their size at the nanometer level, carbon nanodots exhibit significant quantum confinement effects, i.e., their electronic struc­ture and optical properties change significantly. This makes CQDs have tunable fluorescence properties, such as emission wavelength, luminescence intensity, and fluorescence lifetime; they also have good photostability, which can maintain their fluorescence performance under prolonged illumination, and are not easy to fade out or degrade, which makes them suitable for applications such as long-term tracking and micro-imaging; and they are biocompatible with better biocompatibility, and have a lower toxicity to organisms and cells. This makes them have a wide range of potential applications in the biomedical field, such as biomarkers, drug delivery and bioimaging, etc. Meanwhile, CQDs are relatively simple to synthesize and can be prepared by pyrolysis of carbon sources, chemical oxidation or laser stripping. In addition, their surfaces are easy to be functionalized and modified, and different functional groups can be introduced through chemical reactions to achieve specific application requirements.
172 D. Song and H. Li
CQDs have good application prospects in many fields, such as medical imaging technology m, energy development, etc. The main applications of CQDs in biomedicine are biomedical imaging, drug delivery, cancer treatment, gene delivery. This chapter mainly introduces the application of CQDs in drug delivery. On account of its small size and biocompatibility, CQDs is very suitable to act as a carrier in drug delivery, and it also has optical properties, so it is very suitable for detection in vivo. The cytotoxicity of CQDs is the main concern. CQDs cytotoxicity-related research reports were carried out by different researchers and organizations, and satisfactory data and research reports were put forward. The utilization of surface hydrophobic CQDs in combination with hydrophilic polymers is a prerequisite for the preparation of hydrogels. The hydrophilicity of CQDs is related to the hydroxyl and carboxyl groups on their surfaces, and they have high water dispersibility and low cytotoxicity.
Researchers synthesized hydroxyapatite/alginate/CQDs (HA/Alg/CQDs) nanocomposites by coprecipitation method. The synthesized materials have good dispersion and stability, so they are very suitable for use in bone tissue repair [9]. Zhai et al. developed a nuclear-targeted gene delivery platform based on fluo­rescent CQDs. Polyethyleneimine and polyethylene glycol cooperated to passivate the surface of CQDs, which is expected to be an efficient CRISPR/Cas9 delivery vector with in vitro imaging traceability [10]. Bao et al. designed and synthesized a delivery platform with pH-corresponding combination of DOX nanoparticles and CQDs. The synthesized delivery system has high cellular cytotoxicity against tumor cells and can enter the cells by endocytosis [11].

2.2 Carbon Nanotube-Based Polymer Nanocomposite

CNT is a very practical nanomaterial, and it is one of the most important nano-carbon allotropes. CNT is a kind of one-dimensional tubular or cylindrical nanocarbon. It is just a graphene nanosheet with sp tronic, optical, electrical, physical, and other mechanical properties. The unique CNT structure can be categorized into single-walled CNT (SWCNT), double-walled CNT (DWCNT), and multi-walled CNT (MWCNT). The main synthesis techniques of CNTs are chemical vapor deposition, arc displacement, and laser deployment. CNTs have been characterized by interesting properties such as high flexibility, electrical conductivity, thermal conductivity, mechanical strength, and chemical inertness.
A novel green solvent was prepared from SWCNTs doped with molecularly imprinted polymer (MIP) nanocomposites using FB as template molecule. The drug diffusion coefficient produced by SWCNTs reinforced MIP was the lowest in the kinetic analysis of FB release from all samples. Compared with commer­cial FB tablets, the relative bioavailability (F%) of SWCNT-MIP composites is the highest, which is 143.3%. The prepared SWCNT-MIP nanocomposites have the potential to be used as controlled-release devices [12]. H media prepared polypyridine/CNT/alginate multifunctional nanocomposites as a platform for loading metoprolol with a cumulative release of less than 10% after 5 h
2
-bonded carbon atoms. CNT have distinctive elec-
oxidation in micellar
2O2
Carbon Nanomaterial-Based Polymeric Nanocomposites for Drug … 173
under passive conditions. [13]. Magnetic multi-walled carbon nanotube (MMWCNT) hydrogel materials based on polyacrylic acid grafts are a new potential vehicle for drug delivery. The diffusion coefficient of the carbo hydrogel and the release mecha­nism of tetracycline hydrochloride (TCH) were studied. Because the diffusion index of TCH released from MMWCNTs hydrogel is 0.26, its release mechanism is suitable for use in drug delivery [14].

2.3 Graphene Quantum Dot-Based Polymer Nanocomposite

GQDs are carbon nanomaterials formed from graphene fragments. Due to their remarkable fluorescent properties, GQDs have highly adjustable fluorescent proper­ties that can be realized by adjusting parameters such as their size, surface functional groups, and chemical composition. GQDs have good biocompatibility with living organisms and do not cause significant toxic reactions. Due to their large specific surface area and adjustable structural properties, GQDs can be used as efficient carriers for drugs or other molecules with good loading and release ability. Based on these properties, it has a wide range of applications in bio-imaging, drug delivery, and other fields, which provides a good basis for its use in biomedical applications. Naproxen (NAP) was encapsulated in these pH-sensitive nanoparticles by copoly­merization with methacrylic acid in different proportions, which can be used as a suitable carrier for colon-specific drug delivery [15].
For the first time, MgAl-layered double hydroxide, Mn GQDs, and polyaniline were combined into a nanocarrier for the intracellular release of DOX from breast cancer cells, and about 80% of the drug was released in a low pH environment, exhibiting pH-triggered release characteristics [16]. Polypyrrole/ mesoporous silica (PPy/mSiO
) core–shell nanocomposites were used as nanocar-
2
riers of tumor chemotherapy drug methotrexate (MTX). GQDs were introduced into the outer surface of PPy/mSiO
. Under the irradiation of NIR light, the caps of the
2
GQDs were removed and the encapsulated MTX was released from the nanocarriers [17].
An experimental DOX imprinted photoluminescent polymer was developed by a precipitation radical polymerization strategy using GQDs as pH-responsive nanocar­riers. The in vitro drug release to the prepared photoluminescent nanocarriers exhibited a pH-controlled sustained release behavior. Cytotoxicity studies showed that the DOX-loaded nanocarriers exhibited significant cytotoxicity against human lung adenocarcinoma A549 cell line [18, 19]. In summary, GQDs are ideal fillers for polymer nanocomposites because of their superior physical, electrical, and thermal properties. In recent years, graphene/polymer nanocomposites have become a research hotspot for polymer-based nanocomposites.
nanoparticles, N-
3O4
174 D. Song and H. Li
2.4 Metal Organic Framework-Based Polymer
Nanocomposite
MOFs stands for metal–organic skeleton compound. It is self-assembly from a combi­nation of inorganic metal centers and bridging organic ligands. MOFs are a unique type of material that consists of a metallic framework combined with organically linked motifs. Their high degree of porosity, flexibility, and the ability to embed different ligands that confer specific properties make them promising for a wide range of applications in many fields. In recent years, MOFs have become a potential drug delivery carrier in biomedical field due to its large specific surface volume, high porosity, and easy modification. In this paper, the micelles of selenium-containing polymers containing drugs were encapsulated in a MOFs, and the multi-response release of DOX was achieved by using selenium-containing polymers with reDOX triggering properties and MOFs with pH-triggering properties in DDS [20].
Enzymes can also be introduced into MOFs, and some researchers have introduced active enzymes into ZIF-8 to achieve bactericidal properties by releasing Zn inflammatory modulation by homogeneously doping variable valence Mn ions into its framework and showed good therapeutic effects on wound healing in bacterial infec­tions in animal models (Fig. 2)[21]. The development of hybrid nano-systems for the medication-controlled release remains a challenging task. pH-responsive core–shell nanocomposites were prepared by growing zeolite imidazoline framework-8 (ZIF-8) on the aggregated surface of self-assembled polymers. The core is a drug reservoir, and the shell layer is a gateway to prevent premature drug release. Under excitation conditions, the polymers exhibited a slow-release behavior for releasing the drug as compared to the polymers loaded with DOX alone [22].
A drug-release nanocomposite model consists of light-catalyzed TiO the anti-tumor drug Adriamycin and ZIF-8. The system was shown to release an amount of drug sufficient to effectively inhibit the IMR-32 neuroblastoma cells used as a model diseased tissue. This was achieved within 40 min with locally applied UV irradiation, which is a relatively short period of time compared to the release dura­tion of systems without photocatalysts, which typically take from a couple of hours to a couple of days [23]. A porous nanocomposite with magnetic and pH response was produced by grafting of b-cyclodextrin on the surface of Fe
@silica@MIL-
3O4
100(Fe). Temperature and pH effects on the adhesion and release behaviors of the prepared nanocomposite on cefadroxil showed the greatest amount of absorption was observed at room temperature, and the release was rapidly at high temperature [24]. Other MOF-based polymer nanocomposite films were synthesized by using Zr-based UiO-67 as MOF and PU as polymer matrix. The UiO-67@PU nanocom­posites showed prolonged release of bromamine (up to 14 days) [25]. Cerium oxide composites were incorporated into tricarboxylic acid copper-based metal–organic skeletons using a precipitation method. The synthesized Cu-MOF/CeO posites were characterized by various analytical methods to explain their structure, morphology, and thermal behavior. The concentration of 97.9 mg/ml resulted in a 50% cell mortality rate, low cytotoxicity, and good biocompatibility [26].
2+
nanotubes,
2
nanocom-
2
and