Materials Science and Engineering

Mechanical Biomarkers and LHRH/EphA2-Molecular Biomarkers: A Theragnostic Approach for Triple Negative Breast Cancer Diagnosis/Treatment

2024-12-05T22:00:59Z

Mechanical Biomarkers and LHRH/EphA2-Molecular Biomarkers: A Theragnostic Approach for Triple Negative Breast Cancer Diagnosis/Treatment Ezenwafor, Theresa Chikwuo The adhesive interactions between molecular recognition units (such as specific peptides and antibodies) and antigens or other receptors on the surfaces of tumours are of great value in the design of targeted nanoparticles and drugs for the detection and treatment of specific cancers. In addition, the heterogeneous nature of cancer and difficult challenges in early detection has activated a high interest in the development of mechanical biomarkers for cancer diagnosis. This current study presented Luteinizing Hormone Releasing Hormone (LHRH) and Epherin type A2 (EphA2) as a promising biomarker to design a targeted therapy for diagnosis and treatment. Furthermore, the work provides insights through atomic force microscope (AFM) and Nanoindentation (NI) on the application of adhesion forces, adhesion energy, viscosity and statistical deconvolution as diagnostic tools to detect TNBC as well as to characterize it into different histological grades. To appraise these discoveries, TNBC tissue samples of different histological grades were selected (non-neoplastic or Grade 0) and (neoplastic of Grade I to Grade III). To evaluate the receptor overexpression, and their distributions on the human breast tissue extracts, using Immunohistochemistry (IHC) technique, as well as the actin cytoskeletal structures of non tumorigenic and tumorigenic breast tissues (grade I to grade III), a combination of immunofluorescence and confocal microscopy, and atomic force microscopy was used. The adhesion forces between LHRH or EphA2 and human TNBC breast tissues are measured using force microscopy techniques that account for the potential effects of capillary forces due to the presence of water vapor. A combination of nanoindentation and statistical techniques is then used to measure the deformations/viscoelastic properties of non-tumorigenic and human TNBC of different histological grades. The investigation of the underlying magnitude of antigen – antibody interactions corresponding to adhesion energy are also determined using adhesion contact theories/models. A Standard Fluid Model/Anti-Zener Model II is also used to characterize the viscoelastic properties of the non-tumorigenic and tumorigenic TNBC tissues of different grades. The results show that the pull off forces and adhesion energies associated with higher grades of TNBC are shown to be greater than those associated with normal/non-tumorigenic human breast tissues, which were studied as controls. The observed increase in adhesion forces and adhesion energies are also correlated with the increasing incidence of LHRH/EphA2 receptors at higher grades of TNBC. Moreover, the decrease in the viscoelastic properties as well as the actin cytoskeletal structural density observed to be connected to the TNBC tissue histological higher grade are lower than those of non-neoplastic breast tissues. The implications of the results are discussed for the development of targeted nanostructures for the detection and treatment of TNBC, also the potential application of nanoindentation and statistical deconvolution techniques to the development of mechanical biomarkers for TNBC detection /cancer diagnosis. Main Thesis

Valorization of Underutilized Lignocellulosic Biomass Wastes for Biofuel Production

2024-11-28T22:00:52Z

Valorization of Underutilized Lignocellulosic Biomass Wastes for Biofuel Production Uzoagba, Chidiebele Ejikeme The study focuses on utilizing lignocellulose biomass (LCB) as a sustainable feedstock for biofuel production to address fossil fuel depletion, climate change, energy poverty, and environmental issues in Africa. With global energy demand rising and agriculture generating significant waste, the study explores agricultural residues and unconventional biomass sources, such as Prosopis africana, for bioenergy generation. Africa faces severe energy poverty, with millions lacking access to electricity and clean cooking facilities. The research aims to assess the energy potential of these residues and promote circular economy principles through bioenergy production. Methodologically, the study used data from the FAOSTAT database to analyze various crop residues for their suitability in bioenergy generation. It employed empirical analysis and modeling techniques to assess energy potential. For Prosopis africana, proximate, ultimate, and compositional analyses were performed using advanced techniques like scanning electron microscopy, X-Ray diffraction, and thermogravimetric analysis to determine the biomass’s physical, thermal, and chemical properties. Additionally, the hybrid composition of Prosopis africana pod and cowpea husk was evaluated for briquette production, optimizing particle size, binder concentration, and densification pressure using Response Surface Methodology. Results indicate that agricultural residues hold significant potential for bioenergy, supporting sustainable resource utilization and promoting circular economy practices. Prosopis africana exhibited high heating values (15.23 to 20.49 MJ/kg), positioning it as a strong candidate for biofuel production. Optimal briquette properties were achieved with specific particle size, binder concentration, and densification pressure, improving mechanical and combustion characteristics. The study concludes that agricultural residues and Prosopis africana can alleviate Africa’s energy challenges, promote environmental sustainability, and contribute to economic development. The findings offer critical insights into scaling bioenergy production and adopting circular economy principles. Further investigations are ongoing to address socio-economic challenges related to bioenergy adoption. Main Thesis

Laser Induced Heating of Polymer Nanocomposites for Hyperthermia in the Treatment of Triple Negative Breast Cancer

2024-05-30T10:33:56Z

Laser Induced Heating of Polymer Nanocomposites for Hyperthermia in the Treatment of Triple Negative Breast Cancer Onyekanne, Maria Chinyerem Euphemia The work presents the results of an experimental and computational study of the effects of laser-induced heating provided by magnetite polymer-based nanocomposite structures that are being developed for the localized laser-induced hyperthermic treatment of triple-negative breast cancer. Magnetite nanoparticle-reinforced polydimethylsiloxane (PDMS) nanocomposites were fabricated with weight percentages of (1 %, 5 %, and 10 %) magnetite nanoparticles. The fabricated nanocomposites were exposed to incident Near Infrared (NIR) laser beams with well-controlled powers to generate specific elevated temperatures at different times. The mechanical and thermal properties of the different PDMS-based nanocomposites were critically studied. This was because the unique characteristics during the laser-nanocomposite interactions were driven by the both thermal, microstructural, and physicochemical properties (mechanical properties) of the PDMS-based nanocomposites. Under in vitro conditions, our results from the laser-nanocomposites interactions show a decrease in the cell viability of triple-negative breast cancer cells (MDA-MB-231). Using an ex vivo chicken tissue, laser-nanocomposites interactions resulted in well-controlled temperatures in the hyperthermia domain (41 °C and 44°C) in a submillimeter range using a chicken tissue model. Interestingly, laser irradiation and interaction with the nanocomposites did not cause any observed physical damage to the chicken tissue but resulted in significant breast cancer cell dead. The potential in vivo performance of the PDMS nanocomposites was also investigated using computational finite element models of the effects of laser-magnetite nanocomposites interactions on the temperatures and thermal doses experienced by tissues that surround the nanocomposites devices. The outcomes of the experimental studies were validated using the results from the computational analyses. The implications of the results are discussed for the potential design of plasmonic/magnetic-based nanocomposites devices with attractive combinations of mechanical, structural, and thermal properties that are relevant to laser hyperthermia and photo-thermal-ablation for the localized treatment of triple-negative breast cancer tissue. Main Thesis

Biosynthesis of Gold Nanoparticles for Breast Cancer Targeted Drug Delivery

2024-05-30T21:00:37Z

Biosynthesis of Gold Nanoparticles for Breast Cancer Targeted Drug Delivery Dozie-Nwachukwu, Stella Obiageli Although there have been significant efforts in breast cancer treatment over the past many decades, current therapeutic approaches are limited by non-specific systemic distribution, inadequate drug concentrations reaching the tumor and multidrug resistance. This dissertation presents the results of experimental and theoretical studies of the potential applications of biosynthesized gold nanoparticles (AuNPs) and micro encapsulated prodigiosin in targeted drug delivery for the treatment of breast cancer. Gold nanoparticles possess unique physicochemical properties, such as large surface area to mass ratio, and high surface reactivity, presence of surface plasmon resonance (SPR) bands, biocompatibility and ease of surface functionalization, which enables them to diffuse with greater ease inside the tumor cells delivering a high amount of drug selectively to tumor cells with significant reduced toxicity. In this work, the biosynthesis of gold nanoparticles (AuNPs) from plant (Nauclea latifolia) and bacteria (Serratia marcescens) were elucidated. The Nauclea latifolia extract was used to synthesize AuNPs in a record time of < 30 sec, and the sizes of the nanoparticles were in the range of 10 nm – 60 nm. The AuNPs were characterized with UV-visible (UV-Vis) spectroscopy, while the nanoparticle shapes, sizes and polydispersity were elucidated via transmission electron microscopy (TEM) and dynamic light scattering (DLS), respectively. Selected area electron diffraction (SAED) patterns of the AuNPs showed the four-fringe pattern of gold nanoparticles, which corresponds to the face centered cubic (fcc) metal structure of gold ((111), (200), (220), (311)), which confirmed the formation of pure metallic gold nanoparticles. The biosynthesized nanoparticles were functionalized with some molecular recognition units (MRU) (Luteinizing Hormone Releasing Hormone, LHRH and Folic Acid), through thiol linkages or carbodiimide chemistry. The adhesion force between LHRH- or Folate- conjugated AuNPs and the breast cancer cell line iv MDA-MB-231 was determined through atomic force microscopy (AFM). Furthermore, Helium Ion Microscopy (HIM) was used to visualize the clear ring of attachment of the ligands to the gold core. The encapsulation of prodigiosin in chitosan microspheres was equally studied for localized drug delivery. The water-in-oil emulsion technique in which glutaraldehyde was used as a cross-linker was adopted. The morphologies of the resulting microspheres were then studied using scanning electron microscopy (SEM). The average sizes of the microspheres were between 40 µm and 60 µm, while the percentage yields were found to be between 42±2% and 55.5±3%. The resulting encapsulation efficiencies were between 66.7±3% and 90±4%. The in- vitro drug release from the microspheres were characterized using Higuchi and Korsmeyer-Peppas models. The implications of these results are then discussed with a view of developing suitable drug delivery systems that will go a long way to solving the problem of breast cancer in the world, with particular reference to Africa. Main Thesis