Rozprawy doktorskie na temat „Biomedical Applications - Carbon Based Nanomaterials”

Trimetallic nitride endohedral fullerenes (TNT-EMF) have been recognized for their multifunctional capabilities in biomedical applications. Functionalized gadolinium-loaded fullerenes attracted much attention as a potential new nanoplatform for next-generation magnetic resonance imaging (MRI) contrast agents, given their inherent higher 1H relaxivity than most commercial contrast agents. The fullerene cage is an extraordinarily stable species which makes it extremely unlikely to break and release the toxic Gd metal ions into the bioenvironment. In addition, radiolabeled metals could be encapsulated in this robust carbon cage to deliver therapeutic irradiation. In this dissertation, we aim to develop a series of functionalized TNT-EMFs for MRI detection of various pathological conditions, such as brain cancer, chronic osteomyelitis, and gastrointestinal (GI) tract. As a general introduction, Chapter 1 briefly introduces recent progress in developing metallofullerenes for next-generation biomedical applications. Of special interest are MRI contrast agents. Other potential biomedical applications, toxicity, stability and biodistribution of metallofullerenes are also discussed. Finally, the challenges and future outlook of using fullerene in biomedical and diagnosis applications are summarized at the end of this chapter. The large carbon surface area is ideally suited for multiple exo-functionalization approaches to modify the hydrophobic fullerene cage for a more hydrophilic bio-environment. Additionally, peptides and other agents are readily covalently attached to this nanoprobe for targeting applications. Chapter 2 presents the functionalized metallofullerenes conjugated with interleukin-13 peptide exhibits enhanced targeting of U-251 glioblastoma multiforme (GBM) cell lines and can be effectively delivered intravenously in an orthotopic GBM mouse model. Chapter 3 shows, with the specific targeting moiety, the functionalized metallofullerenes can be applied as a non-invasive imaging approach to detect and differentiate chronic post-traumatic osteomyelitis from aseptic inflammation. Fullerene is a powerful antioxidant due to delocalization of the π-electrons over the carbon cage, which can readily react with free radicals and subsequently delivers a cascade of downstream possessions in numerous biomedical applications. Chapter 4 investigates the antioxidative and anti-inflammatory properties of functionalized Gd3N@C80. This nanoplatform would hold great promise as a novel class of theranostic agent in combating oxidative stress and resolving inflammation, given their inherent MRI applications. In chapter 5, Gd3N@C80 is modified with polyethylene glycol (PEG) for working as MRI contrast agents for GI tract. The high molecular weight can prevent any appreciable absorption through the skin or mucosal tissue, and offer considerable advantages for localized agents in the GI tract. Besides the excellent contrast capability, the PEGylated-Gd3N@C80 exhibits outstanding radical scavenging ability, which can potentially eliminate the reactive oxygen species in GI tract. The biodistribution result suggests this nanoplatform can be worked as the potential contrast agent for GI tract at least for 6 hours. A novel amphiphilic Gd3N@C80 derivative is discussed in Chapter 6. It has been noticed for a long time the functionalization Gd3N@C80 contrast agents have higher relaxivity at lower concentrations. The explanation for the concentration dependency is not fully understood. In this work, the amphiphilic Gd3N@C80 derivative is used as the model to investigate the relationship between the relaxivity and concentration of the Gd-based fullerenes. Click chemistry has been extensively used in functionalization due to the high efficiency and technical simplicity of the reaction. Appendix A describes a new type of Sc3N@C80 derivative conducted by employing the click reaction. The structure of Sc3N@C80-alkynyl and Sc3N@C80- alkynyl-benzyl azide are characterized by NMR, MALDI-TOF, UV-Vis, and HPLC. The high yield of the click reaction can provide access to various derivatives which have great potential for application in medical and materials science. The functionalization and characterizations of Ho3N@C80 derivatives are reported in Appendix B. The contrast ability of Ho3N@C80 is directly compared with Gd3N@C80. The Ho-based fullerenes can be performed as the radiotherapeutic agents; the leaching study is performed to test the stability of carbon cage after irradiation. Appendix C briefly shows a new method to develop Gd3N@C80 based targeting platform, which can be used as the probe for chronic post-traumatic osteomyelitis.
PHD

Carbon nanomaterials have attracted significant attention in the past decades for their unique properties and potential applications in many areas. This dissertation addresses the preparation, functionalization and potential biomedical applications of various carbonaceous nanomaterials. Trimetallic nitride template endohedral metallofullerenes (TNT-EMFs, M₃N@C₈₀, M = Gd, Lu, etc.) are some of the most promising materials for biomedical applications. Water-soluble Gd₃N@C₈₀ was prepared by the functionalization with poly(ethylene glycol) (PEG) and hydroxyl groups (Gd₃N@C₈₀[DiPEG(OH)ₓ]). The length of the PEG chain was tuned by changing the molecular weight of the PEG from 350 to 5000. The 1H magnetic resonance relaxivities of the materials were studied at 0.35 T, 2.4 T and 9.4 T. Their relaxivities were found to increase as the molecular weight of the PEG decreased, which is attributed to the increasing aggregate size. The aggregate sizes were confirmed by dynamic light scattering. In vivo study suggested that Gd3N@C₈₀[DiPEG(OH)x] was a good candidate for magnetic resonance imaging (MRI) contrast agents. Another facile method was also developed to functinalize Gd₃N@C₈₀ with both carboxyl and hydroxyl groups by reaction with succinic acyl peroxide and sodium hydroxide thereafter. The product was determined to be Gd₃N@C₈₀(OH)~₂₆(CH₂CH₂COOM)~₁₆ (M = Na, H) by X-ray photoelectron spectrometry. The Gd₃N@C₈₀(OH)~₂₆(CH₂CH₂COOM)~₁₆ also exhibited high relaxivity, and aggregates in water. The research on both pegylated and carboxylated Gd₃N@C₈₀ suggests that aggregation and rotational correlation time plays an important role in relaxation, and the relaxivities and aggregation of the water-soluble metallofullerenes can be tuned by varying the molecular weight of the functionality. TNT-EMFs can be encapsulated inside single-walled carbon nanotubes (SWNTs) to form "peapod" structures by heating the mixture of TNT-EMFs and SWNTs in a vacuum. The peapods were characterized by Raman spectrometry and transmission electron microscopy (TEM). The peapods were then functionalized with hydroxyl groups by a high speed vibration milling (HSVM) method in the presence of KOH. The functionalized Gd-doped peapods exhibited high relaxivites and had an additional advantage of "double carbon wall" protection of the toxic Gd atoms from possible leaking. The HSVM method was modified by using succinic acyl peroxide. The modified HSVM method could functionalize multi-walled carbon nanotubes (MWNT) and single-walled carbon nanohorns (SWNHs) with carboxyl groups. In the presence of N-(3-dimethylaminopropyl)-N'-ethylcarbodiimide hydrochloride (EDC), carboxylate MWNTs and SWNHs could be conjugated with CdSe/ZnS quantum dots (QDs). TNT-EMFs were also encapsulated inside SWNHs to form SWNH peapods. SWNH peapods were functionalized by the modified HSVM method and then were conjugated with CdSe/ZnS QDs. The peapods were characterized by TEM. In vitro and in vivo studies indicated that SWNH peapods could serve as a multimodal diagnostic agent: MRI contrast agent (Gd₃N@C₈₀ encapsulated), radio-active therapeutic agent (Lu₃N@C₈₀ encapsulated) and optical imaging agent (QDs).
Ph. D.

New synthetic advances in the control of nanoparticle size and shape along with the development of new surface modifications facilitates the growing use of nanomaterials in biomedical applications. Of particular interest are functional and biocompatible nanomaterials for sensing, imaging, and drug delivery. The goal of this research is to tailor the function of nanomaterials for biomedical applications by improving the biocompatibility of the systems. Our work demonstrates both a bottom up and a post synthetic approach for incorporating stability, stealth, and biocompatibility to metal based nanoparticle systems. Two main nanomaterial projects are the focus of this dissertation. We first investigated the development of a green synthetic procedure to produce gold nanoparticles for biological imaging and sensing. The size and morphology of gold nanoparticles directly impact their optical properties, which are important for their function as imaging agents or their use in sensor systems. In this project, a synthetic route based on the natural process of biomineralization was developed, where a designed protein scaffold initiates the nucleation and subsequent growth of gold ions. To gain insight into controlling the size and morphology of the synthesized nanoparticles, interactions between the gold ions and the protein surface were studied along with the effect of ionic strength on interactions and then subsequent crystal growth. We are able to control the size and morphology of the gold nanoparticles by altering the concentration or identity of protein scaffold, salt, or reducing agent. The second project involves the design and optimization of metal organic framework nanoparticles for an external stimulus triggered drug delivery system. This work demonstrates the advantages of using surface coatings for improved stability and functionalization. We show that the addition of a polyethylene glycol surface coating improved the colloidal stability and biocompatibility of the system. The nanoparticle was shown to successfully encapsulate a variety of small molecule cargo. This is the first report of photo-triggered degradation and subsequent release of the loaded cargo as a mechanism of stimuli-controlled drug delivery. Each of the aforementioned projects demonstrates the design, synthesis, and optimization of metal-based systems for use in biomedical applications.
Ph. D.

Carbon-based nanomaterials have attracted significant attention due to their unique optical, electrical, thermal and mechanical properties. In recent years, a large number of carbon-based nanomaterials have been investigated including carbon nanotubes, graphitic carbon nitride (g-C3N4), graphene, carbon nanofibers, carbon nanodots (CNDs), heteroatom-doped carbon, and carbon-based materials obtained from biomass etc. The unique and superior properties of such carbon-based materials make them useful for a wide range of applications in the fields such as environmental remediation and energy conversions. Although significant progress has been made over the past decade or so, few drawbacks of carbon-based materials still remain unresolved. For example, as a photocatalyst, the weak van der Waals interactions between adjacent conjugated planes of g-C3N4 and poor electronic properties affect negatively on the photocatalytic activity. Despite a variety of synthetic methods have been investigated, to fabricate undoped and doped carbon-based materials, the efficiency and level of control on the resultant products are far from satisfactory. Majority of these approaches either involve tedious and complex experimental procedures or require using harsh reaction conditions, or possessing low yield production. Furthermore, to achieve heteroatom-doped carbon-based materials, the reported approaches almost exclusively require the use of synthetic chemicals as carbon and heteroatom sources, respectively. The large-scale application of fuel cells and dye-sensitized solar cells (DSSCs) using Pt-based catalysts is hindered by the inherent disadvantages of Pt such as high cost, scarcity and low resistance to crossover effect of methanol molecule. It is therefore highly desirable to realize heteroatom doping by simple, low-cost, high yield and environmentally benign synthesis methods for fabrication of commercially viable carbon-based materials for applications in solar cells and fuel cells.
Thesis (PhD Doctorate)
Doctor of Philosophy (PhD)
Griffith School of Environment
Science, Environment, Engineering and Technology
Full Text

Graphene received increasing attention for sensing and biomedical applications due to its properties. However, the current production methods are resource consuming, struggle to integrate these films into devices, and hardly produce graphene nanostructures (GN) that improve desired film properties like surface area and reactivity. This thesis aims to use a plasma-enhanced technique to produce GN and to explore their potential biological applications. The control of GN using the plasma-enhanced chemical vapour deposition (PECVD) was investigated. Growth parameters were related with the nanostructures properties as well as to the occurrence of the chemical-free transfer (CFT). The ability of GN to induce cellular response was investigated. The biocompatibility of GN was tested and found to be able to support fibroblasts viability at or above 70%. Cell proliferation was correlated to the density of different GN. While the density of horizontal GN had no influence on cell viability, a higher density of vertical GN yielded higher levels of cell viability. Furthermore, proliferation assays showed the ability of the GN surfaces to support bone-cells adhesion and growth. We also demonstrated improvement on mineral deposition that indicates the capability of GN to induce cell differentiation via morphological cues. The GN were also used for biosensing, where different morphologies were optimized to provide extras binding. Horizontal and vertical GN were produced by PECVD and assembled into electrodes via the CFT. The electrochemical sensing shows that both nanostructures perform highly selective measurements with a low limit of detection (picomolar) in a complex biological environment. Furthermore, the sensitivity relied on the density of the GN. This work suggests that plasma techniques are a feasible solution for the production challenges and graphene-based nanostructures are promising for biological applications.

At present, halide perovskite (HP) materials, as a family of promising semiconductors, have been a hot topic in the field of energy and optoelectronic technologies. These materials offer a range of remarkable properties like large absorption coefficients, tunable bandgaps, high carrier mobilities, and long carrier diffusion lengths, etc. Besides these physical properties, due to their low-cost and low-temperature solution processability, HPs are becoming materials of research interests among researchers. Among various optoelectronic applications based on perovskites, photodetectors are the remarkable one which has attached considerable research interests. However, efficient photo-generated carrier extraction and faster carrier transport are the fundamental requirements for good photodetection. Unfortunately, during perovskite thin film (PTF) preparation through the solution process, pinhole generation is prevalent. Therefore, photo-generated carrier face unwanted recombination and trapping. These pinholes are the product of atomic vacancies (AV), and AVs are one of the main causes of hysteresis. In this respect, morphology engineering (ME) of solution-processed PTFs to mitigate hysteresis is mandatory. Exploring different anti-solvents treatments is an option. Carbon nanomaterials (CNM) also can help to reduce unwanted recombination and trappings by improving the TFs’ quality. Among various CNMs, the carbon nanotubes (CNT) are very suitable to make promising composite TFs for high-performance devices. CNTs also help in efficient carrier extraction and faster transmission. Again, all-inorganic perovskites (AIP) offer better stability compared to organic-inorganic hybrid perovskites (OIHP) in an ambient environment. Moreover, the popular Pb-based AIPs pose a potential environmental threat. In this thesis, I am interested in exploring the ME and hybridization of AIPs (CsSnI3) with CNTs and related photodetectors.

In the past decade, the use of nanotechnology as a tool to develop and fabricate new structures and devices for biological sensing and energy applications has become increasingly widespread. In this work, a systematic study has been performed on one-dimensional nanomaterials, with a focus on the development of miniaturized devices with a "bottom up" approach. First, members of the nano - carbon family are utilized for biosensing applications; in particular, carbon nanotubes as well as nitrogen - doped and boron - doped nanocrystalline diamond (NCD) films. These carbon - based materials possess several unique electrochemical properties over other conductive materials which make them suitable for biosensing applications. Single walled carbon nanotubes were deposited on a glass carbon electrode and modified for the detection of Salmonella DNA hybridization. Electrochemical impedance spectroscopy (EIS) was used as the method of detection and a detection limit of 10-9 M was achieved. Nanocrystalline diamond was grown using a microwave enhanced plasma chemical vapor deposition method. The diamond electrodes were doped with either boron or nitrogen to provide substrates and characterization was performed using scanning electron microscopy, atomic force microscopy, Raman spectroscopy, Fourier transform infrared spectroscopy, UV-vis spectroscopy, as well as by electrochemical methods. Modified boron - doped NCD was able to detect Salmonella DNA hybridization via EIS and fluorescent microscopy. The detection limit for these genosensors was found to be 0.4 micrometer complementary DNA. Boron - doped and nitrogen - incorporated nanocrystalline diamond also served as functionalized electrodes for lactic acid detection. It was found that the boron - doped electrodes could detect 0.5 mM lactic acid in a phosphate buffer solution. Second, bismuth antimony nanowires were grown in an anodized alumina template for the fabrication of a thermoelectric cooling device. Bismuth antimony nanowires were chosen due to their high thermoelectric efficiency compared to their bulk material counterpart. The development of a successful anodized template was achieved and EIS was used to diagnose the optimal etch parameters of the barrier oxide layer for nanowire growth. Bismuth antimony nanowires were grown directly on a silicon substrate and a thermoelectric cooling device was fabricated. The nanowires exhibited a thermoelectric efficiency of 0.18 at room temperature.

In der Entwicklung von Technologien für die nachhaltige Erzeugung, Speicherung und Umwandlung von Energie werden Hochleistungskatalysatoren benötigt. Im Rahmen dieser Arbeit werden verschiedene Übergangsmetall-basierte Katalysatoren, namentlich TiO2/Kohlenstoff-Komposite, anorganisch-organische Hybridsysteme auf Basis von NiFe Phosphonaten sowie Ni Phosphide, synthetisiert, charakterisiert und hinsichtlich ihrer photo- und elektrokatalytischen Eigenschaften untersucht. Es wird gezeigt, dass die Grenzflächeneigenschaften der TiO2/C-Komposite signifikant durch die Gestaltung des Heizvorgangs während der Synthese beeinflusst werden. Insbesondere der Einsatz von Mikrowellenstrahlung vermag die Synthese von Kohlenstoff-basierten Materialien positiv zu beeinflussen. Schnelles Erwärmen führt zu stärkeren Wechselwirkungen zwischen Nanopartikeln und Kohlenstoff, einheitlicheren Beschichtungen und kleineren Partikeln mit schmaleren Partikelgrößenverteilungen, wodurch die photokatalytische Aktivität verbessert wird. Schichtartige, hybride NiFe-Phenylphosphonat-Materialien werden ausgehend in Benzylalkohol dargestellt und ihre Aktivität in der OER im basischen Milieu untersucht. Die Hybridpartikel werden in-situ in NiFe-Hydroxid Nanoschichten umgewandelt. Röntgenspektroskopische Untersuchungen deuten auf eine induzierte, teilweise verzerrte Koordinationsumgebung der Metallzentren im Katalysator hin. Die Kombination der synergistischen Effekte zwischen Ni und Fe mit den strukturellen Eigenschaften des Hybridmaterials ermöglicht einen effizienten Katalysator. Weiterhin werden Nickel-Phosphide durch die thermische Behandlung der Phenyl- oder Methylphosphonate des Nickels, welche Schichtstrukturen aufweisen, in H2(5%)/Ar-Atmosphäre synthetisiert. Ni12P5, Ni12P5-Ni2P und Ni2P Nanopartikel, die mit einer dünnen Schicht aus Kohlenstoffmaterial beschichtet sind, werden erhalten. Ni12P5-Ni2P und Ni2P Nanopartikel katalysieren die Wasserstoffentwicklungsreaktion (HER) im Sauren effektiv.
High-performance catalysts play a key role in the development of technologies for sustainable production, storage, and conversion of energy. In this thesis, transition-metal-based catalysts, including TiO2/carbon composites, hybrid organic-inorganic NiFe phosphonates, and Ni phosphides are synthesized, characterized, and investigated in photocatalytic or electrocatalytic reactions. TiO2 is frequently combined with carbon materials, such as reduced graphene oxide (rGO), to produce composites with improved properties. TiO2 is more efficiently stabilized at the surface of rGO than amorphous carbon. Rapid heating of the reaction mixture results in a stronger coupling between the nanoparticles and carbon, more uniform coatings, and smaller particles with narrower size distributions. The more efficient attachment of the oxide leads to better photocatalytic performance. Layered hybrid NiFe-phenylphosphonate compounds are synthesized in benzyl alcohol, and their oxygen evolution reaction (OER) performance in alkaline medium is investigated. The hybrid particles transformed in situ into NiFe hydroxide nanosheets. X-ray absorption spectroscopy measurements suggest the metal sites in the active catalyst inherited partly the distorted coordination. The combination of the synergistic effect between Ni and Fe with the structural properties of the hybrid results in an efficient catalyst that generates a current density of 10 mA cm-2 at an overpotential of 240 mV. Moreover, nickel phosphides are synthesized through thermal treatment under H2(5%)/Ar of layered nickel phenyl- or methylphosphonates that act as single-source precursors. Ni12P5, Ni12P5-Ni2P and Ni2P nanoparticles coated with a thin shell of carbonaceous material are produced. Ni12P5-Ni2P and Ni2P NPs efficiently catalyze the hydrogen evolution reaction (HER) in acidic medium. Co2P and CoP NPs are also synthesized following this method.

This PhD thesis deals with the development of bioactive polysaccharide-based biomaterials for bone tissue and neural tissue engineering. Alginate was chosen for its gel forming properties; hyaluronic acid and chitlac (a lactose-modified chitosan) were chosen for their bioactive properties. The properties of these polysaccharides have been implemented by introducing gelatin, functionalized Carbon Nanotubes (f-CNTs) and silver nanoparticles (nAg). In the first part of the work, the dispersibility and aggregation tendency of f-CNTs have been characterized by means of Low Field Nuclear Magnetic Resonance (LF-NMR). It was also possible to correlate the f-CNTs concentration to the proton transversal relaxation rate of water. Alginate/f-CNTs solutions and hydrogels have been analyzed by LF-NMR, rheology and uniaxial compression tests; these investigations showed that the f-CNTs are able to affect nanocomposite properties depending on their concentration and functionalization. In the second part of the work, the preparation of a bioactive (bridging) implant for the treatment of Spinal Cord Injury is described. Neuronal cells and mesoangioblasts (MABs) engineered for the production of neurotrophines have been cultured and co-cultured on polysaccharide-coated glass substrates in order to evaluate the biological effects of chitlac. Chitlac-coated surfaces where shown to possess higher surface energies if compared to chitosan-coated ones and enable the formation of wider neural networks with improved electrical activity. The co-cultures confirmed the higher bioactivity of chitlac/alginate substrates and the biological role of neurotrophines. Porous scaffolds of alginate/chitlac have been prepared; these scaffolds where shown to be stable in simulated body fluid for over a month. The mechanical properties of rehydrated scaffolds where proved to be similar to those of neural tissue. Biological properties of chitlac substrates enriched with f-CNTs are currently under investigation. In the third part of the work, tridimensional scaffolds and injectable fillers were developed for the treatment of non-critical bone defects. Porous scaffolds with different pore morphologies have been prepared by freeze casting of alginate/HAp hydrogels. Isotropic porosity was obtained by freezing the constructs in a cryostat, while anisotropic porosity was obtained by the Ice Segregation Induced Self Assembly process. Physical, mechanical and biological analyses revealed that the differences in pore morphology determine differences in the mechanical properties of the scaffolds. Biocompatible f-CNTs have been used to implement the isotropic scaffolds; the biological analyses showed that the presence of f-CNTs does not affect scaffold properties. Osteoconductive/antimicrobial injectable bone fillers, based on alginate/HAp microbeads dispersed in polysaccharide mixtures, have been developed. Microbeads were enriched with nAg synthesized in chitlac. Antimicrobial assays proved the antibacterial properties of the microbeads towards bacteria in suspension and on pre-formed biofilms. Biological assays showed the biocompatibility of the microbeads and their ability to sustain osteoblast proliferation. The fillers prepared by dispersing microbeads in polysaccharide mixtures were shown to be easily injectable through surgical syringes. In vivo studies on a rabbit model of non-critical bone defect pointed out the biocompatibility and the osteoconductivity of the composite materials. Further studies are ongoing in order to evaluate the possibility to further implement the bioactive properties of the microbeads by addiction of gelatin.

A prototype 3-dimensional (3D) anode, based on multiwall carbon nanotubes (MWCNTs), for Li-ion batteries (LIBs), with potential use in Electric Vehicles (EVs) was investigated. The unique 3D design of the anode allowed much higher areal mass density of MWCNTs as active materials, resulting in more amount of Li+ ion intake, compared to that of a conventional 2D counterpart. Furthermore, 3D amorphous Si/MWCNTs hybrid structure offered enhancement in electrochemical response (specific capacity 549 mAhg-1). Also, an anode stack was fabricated to further increase the areal or volumetric mass density of MWCNTs. An areal mass density of the anode stack 34.9 mg/cm2 was attained, which is 1,342% higher than the value for a single layer 2.6 mg/cm2. Furthermore, the binder-assisted and hot-pressed anode stack yielded the average reversible, stable gravimetric and volumetric specific capacities of 213 mAhg-1 and 265 mAh/cm3, respectively (at 0.5C). Moreover, a large-scale patterned novel flexible 3D MWCNTs-graphene-polyethylene terephthalate (PET) anode structure was prepared. It generated a reversible specific capacity of 153 mAhg-1 at 0.17C and cycling stability of 130 mAhg-1 up to 50 cycles at 1.7C.

New derivatives of carbon nanostructures: nanotubes, nano-onions and nanocrystalline diamonds were obtained through fluorination and subsequent functionalization with sucrose. Chemically modified nanocarbons show high solubility in water, ethanol, DMF and can be used as biomaterials for medical applications. It was demonstrated that sucrose functionalized nanostructures can find applications in nanocomposites due to improved dispersion enabled by polyol functional groups. Additionally, pristine and chemically derivatized carbon nanotubes were studied as nanofillers in epoxy composites. Carbon nanotubes tailored with amino functionalities demonstrated better dispersion and crosslinking with epoxy polymer yielding improved tensile strength and elastic properties of nanocomposites.

Yes
In 1985, the serendipitous discovery of fullerene triggered the research of carbon structures into the world of symmetric nanomaterials. Consequently, Robert F. Curl, Harold W. Kroto and Richard E. Smalley were awarded the Noble prize in chemistry for their discovery of the buckminsterfullerene (C60 with a cage-like fused-ring structure). Fullerene, as the first symmetric nanostructure in carbon nanomaterials family, opened up new perspectives in nanomaterials field leading to discovery and research on other symmetric carbon nanomaterials like carbon nanotubes and two-dimensional graphene which put fullerenes in the shade, while fullerene as the most symmetrical molecule in the world with incredible properties deserves more attention in nanomaterials studies. Buckyball with its unique structure consisting of sp2 carbons which form a high symmetric cage with different sizes (C60, C70 and so on); however, the most abundant among them is C60 which possesses 60 carbon atoms. The combination of unique properties of this molecule extends its applications in divergent areas of science, especially those related to biomedical engineering. This review aims to be a comprehensive review with a broad interest to the biomedical engineering community, being a substantial overview of the most recent advances on fullerenes in biomedical applications that have not been exhaustively and critically reviewed in the past few years.

New derivatives of carbon nanostructures: nanotubes, nano-onions and nanocrystalline diamonds were obtained through fluorination and subsequent functionalization with sucrose. Chemically modified nanocarbons show high solubility in water, ethanol, DMF and can be used as biomaterials for medical applications. It was demonstrated that sucrose functionalized nanostructures can find applications in nanocomposites due to improved dispersion enabled by polyol functional groups. Additionally, pristine and chemically derivatized carbon nanotubes were studied as nanofillers in epoxy composites. Carbon nanotubes tailored with amino functionalities demonstrated better dispersion and crosslinking with epoxy polymer yielding improved tensile strength and elastic properties of nanocomposites. Reductive functionalization of nanocarbons, also known as Billups reaction, is a powerful method to yield nanomaterials with high degree of surface functionalization. In this method, nanocarbon salts prepared by treatment with lithium or sodium in liquid ammonia react readily with alkyl and aryl halides as well as bromo carboxylic acids. Functionalized materials are soluble in various organic or aqueous solvents. Water soluble nanodiamond derivatives were also synthesized by reductive functionalization of annealed nanodiamonds. Nanodiamond heat pretreatment was necessary to yield surface graphene layers and facilitate electron transfer from reducing agent to the surface of nanoparticles. Other carbon materials such as activated carbon and anthracite coal were also derivatized using reductive functionalization to yield water soluble activated carbon and partially soluble in organic solvents anthracite. It was shown that activated carbon can be effectively functionalized by Billups method. New derivatives of activated carbon can improve water treatment targeting specific impurities and bio active contaminants. It was demonstrated that functionalized carbon nanotubes are suitable for real time radiation measurements. Radiation sensor incorporating derivatized carbon nanotubes is lightweight and reusable. In summary, functionalization of carbon nanomaterials opens new avenues for processing and applications ranging from biomedicine to radiation sensing in space.

博士
國立交通大學
光電工程研究所
104
In the thesis, carbon-based nanomaterials are applied to the counter electrodes (CEs) for dye-sensitized solar cells (DSCs) to reduce the consumption of Pt. The applied carbon-based nanomaterials to CEs include graphene, graphene oxide (GO), and buckypaper (BP). Because of storage limitation of Pt, the cost of DSC manufacturing is increasing. Carbon is an abundant element in the Earth’s crust, and carbon-based nanomaterials have lots of excellent electrical, optical, and electrochemical properties. They exhibit great potential to reduce the Pt consumption in DSCs. In addition to developments of low Pt-loading CE with carbon-based material, the photovoltaic performance and charge dynamics of DSCs with graphene, GO and BP-incorporated CEs are investigate to understand the influences of these carbon-based nanomaterials. The Pt-C composite can reduce the contact resistance of Pt/fluorine-doped tin oxide (FTO) interface, resulting in the enhancements of short-circuit current density and power conversion efficiency of DSC with Pt/few-layer graphene CE (DSCPt/FLG). Solution-processable GO provides a low-cost method to prepare large-quantity and high-transparent carbon source. Pt/GO composites are developed as the high-transparent and high-efficient CEs for bifacial DSCs. DSCPt/GO exhibits the better bifacial photovoltaic behaviors because of the outperformed PCE under rear illumination, attributing to the efficient I3- reduction ability of Pt/GO composite. The solution-processable BP is fabricated with entangled multi-walled carbon nanotubes, providing extreme electroactive surface area for I3- reduction. BPs can increase the I3- reduction rate at CE and suppress the charge recombination at photo-anodes. By applying BP, the DSCBP present a comparable performance to DSCPt, and the Pt-free DSCs are achieved. Accordingly, by applications of graphene, GO, and BP, the Pt consumption in DSCs can be reduced by 75%, 80%, and 100%, respectively. According the experimental results, it is found that the electrocatalytic ability and dimension of carbon-based nanomaterials are important. The naturals of carbon-based nanomaterials lead to the worse electrocatalytic ability to I3- reduction. Therefore, the dimension of CEs becomes critical. The 3-dimensional BP demonstrates the large electroactive surface area can compensate the degradation of electrocatalytic ability, which results in the comparable performance to DSCPt. On the other hand, the low-cost CE manufacturing with inexpensive material can be realized by the solution-processable GO and BP, whereas the complex manufacturing is required to synthesize graphene. Pt consumption is a foreseeable cost issue in DSC deployments. This research demonstrates that carbon-based nanomaterials are the potential materials to reduce Pt consumption in DSCs.

博士
國立臺北科技大學
能源與光電材料國際學生研究所
105
Gold nanoparticles (AuNPs) play a key role in nanotechnology and provide the opportunities for development of a new generation of sensing tools. Besides, the carbon based nanomaterials have attracted tremendous interest in recent years due to its unique electrical, mechanical, chemical and optical properties. These materials are also considered as an ideal matrix for the development of highly sensitive and selective electrochemical sensors and biosensors. This thesis focus on the different synthesis of AuNPs supported carbon based nanomaterials for various sensor and biosensor applications. Mainly, the reduced graphene oxide (RGO) and fullerene (C60) have been utilized as the carbonaceous supporting materials. All materials were characterized by means of various analytical techniques such as scanning electron microscope (SEM), Field emission scanning electron microscope (FESEM), Energy-Dispersive X-Ray Spectroscopy (EDX), Transmission electron microscope (TEM), Atomic-force microscope (AFM), UV-vis spectroscopy, Fourier transform infrared spectroscopy (FTIR), Raman spectroscopy, X-ray diffraction patterns (XRD). The photochemical synthesis of gelatin stabilized gold nanoparticles (GEL-AuNPs) has been employed for the optical spectral activity and electrochemical detection of quercetin (QR). The optical spectral activity of QR, the GEL-AuNPs composite showed a decrease in the absorbance and enhancement in fluorescence region of QR. The spectral activity changes of QR may be caused by the hydrogen bonding formation between amine groups in GEL-AuNPs and –OH and/or carbonyl groups in QR. Moreover, the GEL-AuNPs composite exhibited an excellent electrocatalytic activity towards the detection of QR. To increasing the optical activity of GEL-AuNPs, it was hybrid with RGO by one-pot hydrothermal method. The as-prepared GEL-AuNPs/RGO was demonstrated towards the fluorescence sensing and bioimaging of L-cysteine in live cancer cells, MKN-45 (gastric carcinoma), Colo-205 (colorectal adenocarcinoma) and HCT-116 (colorectal carcinoma). Besides the optical activity, the RGO/AuNPs revealed better electrocatalytic activity thus the RGO was functionalized with phenolic acids to enhance the electrochemical behavior. The hydrothermal method was employed to prepare the gallic acid supported RGO encapsulated AuNPs (GA-RGO/AuNPs). Further, this composite was applied to the detection of dopamine (DA) that showed an excellent electrocatalytic activity towards the oxidation of DA. Instead of GA, the Hemin (HN) was utilized to create the biocatalytic active site in RGO/AuNPs surface. Interestingly, the HN-RGO/AuNPs revealed the direct electrochemistry and excellent electrocatalytic activity towards the detection of hydrogen peroxide (H2O2). Finally, the activated fullerene (AC60) was used to restore the efficiency of RGO, thus, AC60/AuNPs was prepared by a simple and cost effective electrochemical approach. The fabricated AC60/AuNPs showed an excellent electrocatalytic activity towards the detection of hydrazine.

Mestrado em Engenharia Química
Nanoscience has recently experienced a strong development, Magnetic Nanoparticles (MNPs) are one of the most attractive nanomaterials. Focusing on the biomedical applications, this thesis has as main objective the development of new carbon coating methods in order to reach the maximum biocompatibility of MNPs upon synthesis. During the research carried out, two different approaches were evaluated to coat a magnetic core composed of magnetite, using phloroglucinol and glyoxal, following the idea of making the process more sustainable and biocompatible. The difference between those approaches resides on the use of PF-127 as porogen agent during the coating step. However, some significant differences were found for the material synthesized without PF-127 as porogen agent, with the most important one being the lack of stabilization in water, a crucial characteristic of MNPs for biomedical applications. This mishap leaded to the continuation of the methodology development with just one material. The material selected was evaluated as nanocarrier to load and deliver drugs using doxorubicin (DOX) and omeprazole (OME). The delivery was tested at different pH values in order to evaluate its influence, as human body has different pH in a normal tissue (pH 7.4) than in the intracellular tumor environment (pH 4.5) or in its surroundings (pH 6.0).
A nanociência tem experimentado recentemente um forte desenvolvimento. As nanopartículas magnéticas (MNPs) têm sido um dos materiais mais atraentes. Com foco nas aplicações biomédicas, esta tese tem como objetivo principal desenvolver novos métodos de revestimento de carbono para alcançar a máxima biocompatibilidade durante a síntese de MNPs. Durante a pesquisa serão avaliadas duas abordagens diferentes para revestir um núcleo magnético feito de magnetita, as duas utilizan floroglucinol e glioxal, seguindo a ideia de tornar o processo mais sustentável e biocompatível. A diferença entre essas abordagens será sobre o emprego da PF-127 como agente porógeno durante a etapa de revestimento. No entanto, algumas diferenças significativas foram encontradas que o material sintetizado sem a PF-127 como agente porógeno não estava arquivando uma das características mais importantes das MNPs para aplicações biomédicas, a estabilização na água. Este mishap conduziu a continuar a metodologia apenas com um material. O material selecionado foi avaliado para carga e entrega de medicamentos com doxorrubicina e omeprazol. A entrega foi testada em diferentes valores de pH para avaliar sua influência, pois o corpo humano tem pH diferente em um tecido normal (pH 7,4) do que no ambiente tumoral intracelular (pH 4,5) ou em seu entorno (pH 6,0).

碩士
國立臺北科技大學
化學工程研究所
104
Modified material improve the working electrode from electrochemical sensor. This study has used plant extracts as a reducing agent to synthesize metal nanoparticle（ex: Ag and Au）as a modified material. This process is simple, low cost, non-toxic and environmentally friendly. Silver nanoparticles were used in modified material for 4-nitrophenol sensor. The linear range, detection limit and sensitivity are estimated as 0.09–82.5 μM, 0.06 μM and 3.0 μA mM-1 cm2 respectively. Gold nanoparticles and graphene oxide used in modified composites for chloramphenicol sensor. The linear range, detection limit and sensitivity are estimated as 1.5–2.95 μM, 0.25 μM and 3.81 μA mM-1 cm2 respectively. Furthermore, the Cadmium hydroxide/reduced graphene oxide composites have been prepared using a simple co-precipitation method. This composites used in N-phenylacetamide sensor. The linear range, detection limit and sensitivity are estimated as 0.1–102 μM, 0.20 μM and 24.452 μA mM-1 cm2 respectively.

Since the discovery of carbon nanotubes (CNTs), they have gained much interest in many science and engineering fields. The modification of CNTs by introducing different functional groups to their surface is important for CNTs to be tailored to fit the need of specific applications. This dissertation presents several CNT-based systems that can provide biomedical and environmental advantages. In this research, polyethylenimine (PEI) and polyvinyl alcohol (PVA) were used to coat CNTs through hydrogen bonding. The release of doxorubicin (DOX, an anticancer drug) from this system was controlled by temperature. This system represents a promising method for incorporating stimuli triggered polymer-gated CNTs in controlled release applications. To create an acid responsive system CNTs were coated with 1,2-Distearoyl-snglycero- 3-Phosphoethanolamine-N-[Amino(Polyethylene glycol)2000]-(PE-PEG) and Poly(acrylic acid) modified dioleoy lphosphatidyl-ethanolamine (PE-PAA). An acidlabile linker was used to cross-link PAA, forming ALP@CNTs, thus making the system acid sensitive. The release of DOX from ALP@CNTs was found to be higher in an acidic environment. Moreover, near infrared (NIR) light was used to enhance the release of DOX from ALP@CNTs. A CNT-based membrane with controlled diffusion was prepared in the next study. CNTs were used as a component of a cellulose/gel membrane due to their optical property, which allows them to convert NIR light into heat. Poly(Nisopropylacrylamide) (PNIPAm) was used due to its thermo-sensitivity. The properties of both the CNTs and PNIPAm’s were used to control the diffusion of the cargo from the system, under the influence of NIR. CNTs were also used to fabricate an antibacterial agent, for which they were coated with polydopamine (PDA) and decorated with silver particles (Ag). Galactose (Gal) terminated with thiol groups conjugated with the above system was used to strengthen the bacterial targeting ability. The antibacterial activity of Ag/Gal@PDA@CNTs was examined on Escherichia coli. NIR was used to enhance the antibacterial activity of Ag/Gal@PDA@CNTs. Finally, CNTs were used as a support for methyl orange (MO) and palladium catalysts (Pd). MO was used due to its ability to enhance the catalyst activity. Pd@CNTs composites were used to test the reduction rate of nitrite with and without the addition MO. The results showed that over repeated cycles of nitrite reduction, the activity enhancement was lost. In summary, CNTs are promising building blocks for preparation of smart and stimuli responsive systems that have potential for a wide range of applications. The methods presented are simple and can be scaled up for industrial processing purposes.