Biosynthesis of Gold Nanoparticles for Breast Cancer Targeted Drug Delivery

Abstract

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 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.